Vaccines

20 pages, 1439 KiB

Open AccessEditor’s ChoiceArticle

Progress and Challenges in Measles and Rubella Elimination in the WHO European Region

by Mark Muscat, Myriam Ben Mamou, Catharina Reynen-de Kat, Dragan Jankovic, José Hagan, Simarjit Singh and Siddhartha Sankar Datta

Vaccines 2024, 12(6), 696; https://doi.org/10.3390/vaccines12060696 - 20 Jun 2024

Cited by 9 | Viewed by 3570

Abstract

The elimination of both measles and rubella remains a priority for all 53 Member States of the World Health Organization (WHO) European Region. To provide an update on the epidemiological status of measles and rubella in the Region, we reviewed surveillance data on [...] Read more.

The elimination of both measles and rubella remains a priority for all 53 Member States of the World Health Organization (WHO) European Region. To provide an update on the epidemiological status of measles and rubella in the Region, we reviewed surveillance data on both diseases for 2023 submitted monthly by national surveillance institutions. We analyzed the cases of measles and rubella for 2023 by age group, case classification, vaccination, hospitalization, and importation status and report on measles-related deaths. In 2023, 60,860 measles cases, including 13 fatal cases, were reported in 41 countries. Most cases (95%; n = 57,584) were reported by six countries: Azerbaijan, Kazakhstan, Kyrgyzstan, Romania, the Russian Federation, and Türkiye. Of the 60,848 cases with data on age, 19,137 (31%) were 1–4 years old and 12,838 (21%) were 5–9 years old. A total of 10,412 (17%) were 20 years and older. The genotypes identified in the Region were largely dominated by D8 variants (n = 1357) and the remainder were B3 variants (n = 221). In 2023, 345 rubella cases were reported by 17 countries, mostly from Poland, Kyrgyzstan, Tajikistan, Türkiye, and Ukraine. A total of 262 cases (76%) were classified as clinically compatible and 79 (23%) were laboratory-confirmed. To achieve the elimination of measles and rubella in the Region, political commitment needs to be revived to enable urgent efforts to increase vaccination coverage, improve surveillance and outbreak preparedness, and respond immediately to outbreaks. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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15 pages, 2848 KiB

Open AccessEditor’s ChoiceArticle

SARS-CoV-2-Specific Immune Cytokine Profiles to mRNA, Viral Vector and Protein-Based Vaccines in Patients with Multiple Sclerosis: Beyond Interferon Gamma

by Georges Katoul Al Rahbani, Christina Woopen, Marie Dunsche, Undine Proschmann, Tjalf Ziemssen and Katja Akgün

Vaccines 2024, 12(6), 684; https://doi.org/10.3390/vaccines12060684 - 19 Jun 2024

Cited by 3 | Viewed by 2265

Abstract

Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of [...] Read more.

Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of broad cytokine profiles in pwMS on various DMTs. We examined SARS-CoV-2-specific T cell responses in whole blood cultures characterized by the release of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-13, IL-17A, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), as well as antibodies (AB) targeting the SARS-CoV-2 spike protein in pwMS following either two or three doses of mRNA or viral vector vaccines (VVV). For mRNA vaccination non-responders, the NVX-CoV2373 protein-based vaccine was administered, and immune responses were evaluated. Our findings indicate that immune responses to SARS-CoV-2 vaccines in pwMS are skewed towards a Th1 phenotype, characterized by IL-2 and IFN-γ. Additionally, a Th2 response characterized by IL-5, and to a lesser extent IL-4, IL-10, and IL-13, is observed. Therefore, the measurement of IL-2 and IL-5 levels could complement traditional IFN-γ assays to more comprehensively characterize the cellular responses to SARS-CoV-2 vaccines. Our results provide a comprehensive cytokine profile for pwMS receiving different DMTs and offer valuable insights for designing vaccination strategies in this patient population. Full article

(This article belongs to the Special Issue Interferon Responses after Vaccine Administration)

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17 pages, 3627 KiB

Open AccessEditor’s ChoiceReview

Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas

by Kawaljit Kaur, Jashan Sanghu, Sanaz Memarzadeh and Anahid Jewett

Vaccines 2024, 12(6), 677; https://doi.org/10.3390/vaccines12060677 - 18 Jun 2024

Cited by 6 | Viewed by 2882

Abstract

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they [...] Read more.

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

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32 pages, 2118 KiB

Open AccessEditor’s ChoiceReview

An Overview of the Strategies to Boost SARS-CoV-2-Specific Immunity in People with Inborn Errors of Immunity

by Emma Chang-Rabley, Menno C. van Zelm, Emily E. Ricotta and Emily S. J. Edwards

Vaccines 2024, 12(6), 675; https://doi.org/10.3390/vaccines12060675 - 18 Jun 2024

Cited by 3 | Viewed by 2552

Abstract

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. [...] Read more.

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still unknown. Given their susceptibility to severe COVID-19, strategies such as immunoglobulin replacement therapy (IgRT) and monoclonal antibodies have been employed to provide passive immunity, and protection against both current and emerging variants. This review examines the efficacy of COVID-19 vaccines and antibody-based therapies in IEI patients, their capacity to recognize viral variants, and the necessary advances required for the ongoing protection of people with IEIs. Full article

(This article belongs to the Special Issue Influence of Natural and/or Vaccine Immunity on the Dynamics of SARS-CoV-2)

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15 pages, 5690 KiB

Open AccessEditor’s ChoiceArticle

mRNA Vaccine for Alzheimer’s Disease: Pilot Study

by Armine Hovakimyan, Garri Chilingaryan, Olga King, Joia Kai Capocchi, Jean Paul Chadarevian, Hayk Davtyan, Roman Kniazev, Michael G. Agadjanyan and Anahit Ghochikyan

Vaccines 2024, 12(6), 659; https://doi.org/10.3390/vaccines12060659 - 14 Jun 2024

Cited by 5 | Viewed by 5357

Abstract

The escalating global healthcare challenge posed by Alzheimer’s Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved [...] Read more.

The escalating global healthcare challenge posed by Alzheimer’s Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved lecanemab significantly reduces Aβ aggregates from the brains of early AD patients administered biweekly with this humanized monoclonal antibody. Although the clinical benefits noted in these trials have been modest, researchers have emphasized the importance of preventive immunotherapy. Importantly, data from immunotherapy studies have shown that antibody concentrations in the periphery of vaccinated people should be sufficient for targeting Aβ in the CNS. To generate relatively high concentrations of antibodies in vaccinated people at risk of AD, we generated a universal vaccine platform, MultiTEP, and, based on it, developed a DNA vaccine, AV-1959D, targeting pathological Aβ, completed IND enabling studies, and initiated a Phase I clinical trial with early AD volunteers. Our current pilot study combined our advanced MultiTEP technology with a novel mRNA approach to develop an mRNA vaccine encapsulated in lipid-based nanoparticles (LNPs), AV-1959LR. Here, we report our initial findings on the immunogenicity of 1959LR in mice and non-human primates, comparing it with the immunogenicity of its DNA counterpart, AV-1959D. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

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14 pages, 1698 KiB

Open AccessEditor’s ChoiceSystematic Review

Therapeutic Vaccines for HPV-Associated Cervical Malignancies: A Systematic Review

by Souhail Alouini and Chantal Pichon

Vaccines 2024, 12(4), 428; https://doi.org/10.3390/vaccines12040428 - 17 Apr 2024

Cited by 11 | Viewed by 5063

Abstract

Importance: Despite widespread prophylactic vaccination, cervical cancer continues to be a major health problem with considerable mortality. Currently, therapeutic vaccines for HPV-associated cervical malignancies are being evaluated as a potential complement to the standard treatment. Objective: The present systematic review was conducted on [...] Read more.

Importance: Despite widespread prophylactic vaccination, cervical cancer continues to be a major health problem with considerable mortality. Currently, therapeutic vaccines for HPV-associated cervical malignancies are being evaluated as a potential complement to the standard treatment. Objective: The present systematic review was conducted on randomized controlled trials (RCTs) to investigate the effects of therapeutic vaccines on the treatment of patients with cervical cancer and cervical intraepithelial neoplasia (CIN) of Grades 2 and 3. Evidence Review: The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched. Only articles in English published up until 31 January 2024 were selected. Also, reference lists of the selected original papers and recent review articles were manually searched for additional sources. Data on study characteristics were extracted from the selected articles. Data on outcomes of interest were synthesized, and vaccine efficacy endpoints (histological lesion regression, clinical response, and overall survival) were selected as the basis for grouping the studies. Findings: After screening 831 articles, nine RCTs with 800 participants were included, of which seven studies with 677 participants involved CIN2 and CIN3 and examined lesion regression to ≤CIN1 as the efficacy endpoint. Results of two of these studies were deemed to have a high risk of bias, and another one did not contain statistical analyses. Results of the other four studies were quantitively synthesized, and the pooling of p-values revealed a significant difference between the vaccine and placebo groups in terms of lesion regression (p-values of 0.135, 0.049, and 0.034 in RCTs, yielding a combined p-value of 0.010). The certainty of the evidence was rated as moderate. Patients with advanced cervical cancers were studied in two RCTs with 123 participants. Clinical response and overall survival were taken as endpoints, and the results were reported as not significant. The certainty of the evidence of these results was rated as very low, mainly due to the very small number of events. All studies reported good tolerance for the vaccines. Conclusions and Relevance: The results indicate the potential for therapeutic vaccines in the regression of CIN2 and CIN3 lesions. Moreover, a potential gap in evidence is identified regarding the very low number of RCTs in patients with advanced cervical cancer. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

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14 pages, 927 KiB

Open AccessEditor’s ChoiceArticle

Impact of HPV Vaccination on the Incidence of High-Grade Cervical Intraepithelial Neoplasia (CIN2+) in Women Aged 20–25 in the Northern Part of Norway: A 15-Year Study

by Marte Pettersen Mikalsen, Gunnar Skov Simonsen and Sveinung Wergeland Sørbye

Vaccines 2024, 12(4), 421; https://doi.org/10.3390/vaccines12040421 - 16 Apr 2024

Cited by 5 | Viewed by 4367

Abstract

Background: Human papillomavirus (HPV), the most prevalent sexually transmitted infection globally, is a key risk factor for high-grade cervical lesions and cervical cancer. Since 2009, HPV vaccination has been part of the national immunization program for girls in 7th grade in Norway (women [...] Read more.

Background: Human papillomavirus (HPV), the most prevalent sexually transmitted infection globally, is a key risk factor for high-grade cervical lesions and cervical cancer. Since 2009, HPV vaccination has been part of the national immunization program for girls in 7th grade in Norway (women born 1997 and later). This study aimed to assess the impact of HPV vaccination on the incidence of high-grade cervical precursors (CIN2+) among women aged 20–25 in Troms and Finnmark over a 15-year period. Materials and Methods: In this time series study, we analyzed cervical screening data from 15,328 women aged 20–25 in Troms and Finnmark, collected between 2008 and 2022. Statistical methods, including linear and logistic regression, were employed to evaluate changes in cervical intraepithelial neoplasia grade 2 and worse (CIN2+) incidence and compare risks between vaccine-offered cohorts and pre-vaccine cohorts. Results: The incidence of CIN2+ initially increased from 31 cases per year in 2008 to 110 cases in 2018, then significantly decreased to 44 cases per year by 2022 (p < 0.01). Women in pre-vaccine cohorts had a substantially higher risk of CIN2+ (OR 9.02, 95% CI 5.9–13.8) and CIN3+ (OR 19.6, 95% CI 7.3–52.6). Notably, no vaccinated women with CIN2+ tested positive for HPV types 16 or 18. Furthermore, none of the 13 cervical cancer cases recorded during the study were from the vaccinated cohorts. Interpretation: The findings suggest a significant reduction in the incidence of high-grade cervical precursors following the introduction of the HPV vaccine in Norway’s national immunization program, highlighting its effectiveness in cervical cancer prevention among young women in Northern Norway. Full article

(This article belongs to the Special Issue Vaccination Progress in COVID-19 and HPV)

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25 pages, 5509 KiB

Open AccessEditor’s ChoiceArticle

Design and Characterization of a New Formulation for the Delivery of COVID-19-mRNA Vaccine to the Nasal Mucosa

by Ayça Altay Benetti, Eugene Yang Zhi Tan, Zi Wei Chang, Ki Hyun Bae, Ma Thinzar Thwin, Ram Pravin Kumar Muthuramalingam, Kuo-Chieh Liao, Yue Wan, Lisa F. P. Ng, Laurent Renia, Jianping Liu, Xiaoyuan Chen, Yi Yan Yang, Kevin P. White and Giorgia Pastorin

Vaccines 2024, 12(4), 409; https://doi.org/10.3390/vaccines12040409 - 12 Apr 2024

Cited by 9 | Viewed by 4816

Abstract

Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cells (e.g., dendritic [...] Read more.

Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cells (e.g., dendritic cells and macrophages). In this project, we aimed at developing novel lipid-based nanoformulations for mRNA delivery to counteract the pandemic caused by SARS-CoV-2 virus. The formulations achieved a mRNA encapsulation efficiency of ~80.2% with chitosan-lipid nanoparticles, as measured by the RiboGreen assay. Furthermore, the evaluation of SARS-CoV-2 Spike (S) receptor-binding domain (RBD) expression via ELISA for our vaccine formulations showed transfection levels in human embryonic kidney cells (HEK 293), lung carcinoma cells (A549), and dendritic cells (DC 2.4) equal to 9.9 ± 0.1 ng/mL (174.7 ± 1.1 fold change from untreated cells (UT)), 7.0 ± 0.2 ng/mL (128.1 ± 4.9 fold change from UT), and 0.9 ± 0.0 ng/mL (18.0 ± 0.1 fold change from UT), respectively. Our most promising vaccine formulation was also demonstrated to be amenable to lyophilization with minimal degradation of loaded mRNA, paving the way towards a more accessible and stable vaccine. Preliminary in vivo studies in mice were performed to assess the systemic and local immune responses. Nasal bronchoalveolar lavage fluid (BALF) wash showed that utilizing the optimized formulation resulted in local antibody concentrations and did not trigger any systemic antibody response. However, if further improved and developed, it could potentially contribute to the management of COVID-19 through nasopharyngeal immunization strategies. Full article

(This article belongs to the Special Issue DNA Vaccines against Infectious Diseases)

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12 pages, 967 KiB

Open AccessEditor’s ChoiceArticle

Effectiveness of Nirsevimab Immunoprophylaxis Administered at Birth to Prevent Infant Hospitalisation for Respiratory Syncytial Virus Infection: A Population-Based Cohort Study

by Guillermo Ezpeleta, Ana Navascués, Natividad Viguria, Mercedes Herranz-Aguirre, Sergio Enrique Juan Belloc, Juan Gimeno Ballester, Juan Carlos Muruzábal, Manuel García-Cenoz, Camino Trobajo-Sanmartín, Aitziber Echeverria, Iván Martínez-Baz, Noelia Vera-Punzano, Itziar Casado, Héctor López-Mendoza, Carmen Ezpeleta and Jesús Castilla

Vaccines 2024, 12(4), 383; https://doi.org/10.3390/vaccines12040383 - 4 Apr 2024

Cited by 48 | Viewed by 9781

Abstract

Respiratory syncytial virus (RSV) infection is a frequent cause of hospitalisation in the first few months of life; however, this risk rapidly decreases with age. Nirsevimab immunoprophylaxis was approved in the European Union for the prevention of RSV-associated lower respiratory tract disease in [...] Read more.

Respiratory syncytial virus (RSV) infection is a frequent cause of hospitalisation in the first few months of life; however, this risk rapidly decreases with age. Nirsevimab immunoprophylaxis was approved in the European Union for the prevention of RSV-associated lower respiratory tract disease in infants during their first RSV season. We evaluated the effectiveness of nirsevimab in preventing hospitalisations for confirmed RSV infection and the impact of a strategy of immunisation at birth. A population-based cohort study was performed in Navarre, Spain, where nirsevimab was offered at birth to all children born from October to December 2023. Cox regression was used to estimate the hazard ratio of hospitalisation for PCR-confirmed RSV infection between infants who received and did not receive nirsevimab. Of 1177 infants studied, 1083 (92.0%) received nirsevimab. The risk of hospitalisation for RSV was 8.5% (8/94) among non-immunised infants versus 0.7% (8/1083) in those that were immunised. The estimated effectiveness of nirsevimab was 88.7% (95% confidence interval, 69.6–95.8). Immunisation at birth of infants born between October and December 2023 prevented one hospitalisation for every 15.3 immunised infants. Immunisation of children born from September to January might prevent 77.5% of preventable hospitalisations for RSV in infants born in 2023–2024. These results support the recommendation of nirsevimab immunisation at birth to children born during the RSV epidemic or in the months immediately before to prevent severe RSV infections and alleviate the overload of paediatric hospital resources. Full article

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16 pages, 4341 KiB

Open AccessEditor’s ChoiceArticle

Development and Evaluation of an Immunoinformatics-Based Multi-Peptide Vaccine against Acinetobacter baumannii Infection

by Sean Jeffreys, Megan P. Tompkins, Jadelynn Aki, Sara B. Papp, James P. Chambers, M. Neal Guentzel, Chiung-Yu Hung, Jieh-Juen Yu and Bernard P. Arulanandam

Vaccines 2024, 12(4), 358; https://doi.org/10.3390/vaccines12040358 - 27 Mar 2024

Cited by 12 | Viewed by 3226

Abstract

Multi-drug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. Due to its environmental persistence, virulence, and limited treatment options, this organism causes both increased patient mortality and incurred healthcare costs. Thus, prophylactic vaccination could be ideal for intervention against MDR [...] Read more.

Multi-drug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. Due to its environmental persistence, virulence, and limited treatment options, this organism causes both increased patient mortality and incurred healthcare costs. Thus, prophylactic vaccination could be ideal for intervention against MDR Acinetobacter infection in susceptible populations. In this study, we employed immunoinformatics to identify peptides containing both putative B- and T-cell epitopes from proteins associated with A. baumannii pathogenesis. A novel Acinetobacter Multi-Epitope Vaccine (AMEV2) was constructed using an A. baumannii thioredoxin A (TrxA) leading protein sequence followed by five identified peptide antigens. Antisera from A. baumannii infected mice demonstrated reactivity to rAMEV2, and subcutaneous immunization of mice with rAMEV2 produced high antibody titer against the construct as well as peptide components. Immunization results in increased frequency of IL-4-secreting splenocytes indicative of a Th2 response. AMEV2-immunized mice were protected against intranasal challenge with a hypervirulent strain of A. baumannii and demonstrated reduced bacterial burden at 48 h. In contrast, all mock vaccinated mice succumbed to infection within 3 days. Results presented here provide insight into the effectiveness of immunoinformatic-based vaccine design and its potential as an effective strategy to combat the rise of MDR pathogens. Full article

(This article belongs to the Special Issue Novel Vaccines for Infectious Pathogens)

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20 pages, 3867 KiB

Open AccessEditor’s ChoiceArticle

Microfluidic Synthesis of Scalable Layer-by-Layer Multiple Antigen Nano-Delivery Platform for SARS-CoV-2 Vaccines

by Yang Xu, Kazuya Masuda, Christine Groso, Rick Hassan, Ziyou Zhou, Kelsey Broderick, Moriya Tsuji and Christopher Tison

Vaccines 2024, 12(3), 339; https://doi.org/10.3390/vaccines12030339 - 21 Mar 2024

Cited by 6 | Viewed by 3490

Abstract

The COVID-19 outbreak was a global pandemic with wide-ranging healthcare implications. Although several mRNA-based vaccines delivered using lipid nanoparticles (LNP) have been approved and demonstrated efficacy at reducing the severity and spread of infection, continued rapid viral evolution and disadvantages currently associated with [...] Read more.

The COVID-19 outbreak was a global pandemic with wide-ranging healthcare implications. Although several mRNA-based vaccines delivered using lipid nanoparticles (LNP) have been approved and demonstrated efficacy at reducing the severity and spread of infection, continued rapid viral evolution and disadvantages currently associated with LNP delivery vehicles (such as toxicity) are driving the design of next-generation SARS-CoV-2 vaccines. Herein, we describe the development of a trimethylated chitosan-based nanoparticle layer-by-layer (LbL) delivery platform for multiple antigens as a scalable and safe COVID-19 vaccine, known as, “LbL-CoV19”. These vaccine candidates have been demonstrated to be biocompatible, safe, and effective at stimulating both humoral and cellular responses for protection in preclinical studies. Preliminary results also indicate that LbL-CoV19 can potentially achieve rapid, long-lasting, and broad protection against the SARS-CoV-2 challenge. The “plug-and-play” platform technology is well suited to preparedness for future pandemics and disease outbreaks. Full article

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20 pages, 744 KiB

Open AccessEditor’s ChoiceReview

Recent Scientific Advancements towards a Vaccine against Group A Streptococcus

by Jingyi Fan, Istvan Toth and Rachel J. Stephenson

Vaccines 2024, 12(3), 272; https://doi.org/10.3390/vaccines12030272 - 5 Mar 2024

Cited by 16 | Viewed by 7946

Abstract

Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the [...] Read more.

Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the potential to elicit fatal autoimmune sequelae diseases (including rheumatic fever and rheumatic heart diseases) due to recurrent GAS infections, leading to high morbidity and mortality of young children and the elderly worldwide. Antibiotic drugs are the primary method of controlling and treating the early stages of GAS infection; however, the recent identification of clinical GAS isolates with reduced sensitivity to penicillin-adjunctive antibiotics and increasing macrolide resistance is an increasing threat. Vaccination is credited as the most successful medical intervention against infectious diseases since it was discovered by Edward Jenner in 1796. Immunisation with an inactive/live-attenuated whole pathogen or selective pathogen-derived antigens induces a potent adaptive immunity and protection against infectious diseases. Although no GAS vaccines have been approved for the market following more than 100 years of GAS vaccine development, the understanding of GAS pathogenesis and transmission has significantly increased, providing detailed insight into the primary pathogenic proteins, and enhancing GAS vaccine design. This review highlights recent advances in GAS vaccine development, providing detailed data from preclinical and clinical studies across the globe for potential GAS vaccine candidates. Furthermore, the challenges and future perspectives on the development of GAS vaccines are also described. Full article

(This article belongs to the Special Issue Recent Scientific Advancements towards a Vaccine against Group A Streptococcus)

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11 pages, 1072 KiB

Open AccessEditor’s ChoiceArticle

Prolonged SARS-CoV-2 T Cell Responses in a Vaccinated COVID-19-Naive Population

by Vassiliki C. Pitiriga, Myrto Papamentzelopoulou, Kanella E. Konstantinakou, Irene V. Vasileiou, Alexandros D. Konstantinidis, Natalia I. Spyrou and Athanasios Tsakris

Vaccines 2024, 12(3), 270; https://doi.org/10.3390/vaccines12030270 - 4 Mar 2024

Cited by 5 | Viewed by 2775

Abstract

Introduction: Exploring T cell response duration is pivotal for understanding immune protection evolution in natural SARS-CoV-2 infections. The objective of the present study was to analyze the T cell immune response over time in individuals who were both vaccinated and COVID-19-naive and had [...] Read more.

Introduction: Exploring T cell response duration is pivotal for understanding immune protection evolution in natural SARS-CoV-2 infections. The objective of the present study was to analyze the T cell immune response over time in individuals who were both vaccinated and COVID-19-naive and had undetectable levels of SARS-CoV-2 IgG antibodies at the time of testing. Methods: We performed a retrospective descriptive analysis using data extracted from the electronic medical records of consecutive adult individuals who underwent COVID-19 immunity screening at a private healthcare center from September 2021 to September 2022. The study participants were divided into three groups according to the post-vaccination time period, as follows: group A (up to 3 months), group B (3–6 months), and group C (>6 months). T cell response was evaluated using the IGRA methodology T-SPOT^®.COVID. Results: Of the total number of subjects (n = 165), 60/165 (36.4%) had been vaccinated in the last 3 months (group A), 57/165 (34.5%) between 3 and 6 months (group B), and 48/165 (29.1%) at least 6 months prior to the examination day (group C). T cell positivity was reported in 33/60 (55.0%) of group A, 45/57 (78.9%) of group B, and 36/48 (75%) of group C (p < 0.007). No statistically significant differences were revealed in the spot-forming cell (SFC) count among groups, with mean SFC counts of 75.96 for group A, 89.92 for group B, and 83.58 for group C (Kruskal–Wallis test, p = 0.278). Conclusions: Our findings suggest that cellular immunity following SARS-CoV-2 vaccination may endure for at least six months, even in the presence of declining or absent IgG antibody levels. Full article

(This article belongs to the Special Issue Safety and Immune Responses of Vaccines)

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20 pages, 557 KiB

Open AccessEditor’s ChoiceSystematic Review

Barriers to and Facilitators for Accessing HPV Vaccination in Migrant and Refugee Populations: A Systematic Review

by Davide Graci, Nicolò Piazza, Salvatore Ardagna, Alessandra Casuccio, Anton Drobov, Federica Geraci, Angelo Immordino, Alessandra Pirrello, Vincenzo Restivo, Riccardo Rumbo, Rosalba Stefano, Roberta Virone, Elena Zarcone and Palmira Immordino

Vaccines 2024, 12(3), 256; https://doi.org/10.3390/vaccines12030256 - 29 Feb 2024

Cited by 13 | Viewed by 3685

Abstract

Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally and a primary cause of cervical cancer, which ranks fourth among tumors in both incidence and mortality. Despite the availability of effective vaccines worldwide, HPV vaccination rates vary, especially among migrant and [...] Read more.

Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally and a primary cause of cervical cancer, which ranks fourth among tumors in both incidence and mortality. Despite the availability of effective vaccines worldwide, HPV vaccination rates vary, especially among migrant and refugee populations. Indeed, migrant status may act as a determinant against accessing vaccinations, among many other factors. The objective of this paper is to evaluate barriers to and facilitators for accessing HPV vaccination in migrant and refugee populations. A systematic review of the existing peer-reviewed academic literature was conducted according to the PRISMA 2020 guidelines in which we examined thirty-four studies to evaluate HPV vaccination rates in these populations and identify factors acting as barriers or facilitators. Key determinants include socio-economic status and health literacy. Communication barriers, including language and cultural factors, also impact access to information and trust in the health workforce. Understanding and considering these factors is crucial for developing proper and inclusive vaccination strategies to ensure that no population is overlooked. Full article

(This article belongs to the Special Issue Vaccine Literacy and Social–Cognitive Determinants of Vaccination)

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17 pages, 744 KiB

Open AccessEditor’s ChoiceReview

Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination

by Minako Yamaoka-Tojo and Taiki Tojo

Vaccines 2024, 12(3), 252; https://doi.org/10.3390/vaccines12030252 - 28 Feb 2024

Cited by 7 | Viewed by 9287

Abstract

Herpes zoster, induced by the reactivation of the varicella-zoster virus (VZV), is a unilaterally distributed vesicular rash that can cause multiple complications. VZV not only causes neurological problems, including postherpetic neuralgia and ocular zoster, but also causes inflammatory vasculopathy and increases the incidence [...] Read more.

Herpes zoster, induced by the reactivation of the varicella-zoster virus (VZV), is a unilaterally distributed vesicular rash that can cause multiple complications. VZV not only causes neurological problems, including postherpetic neuralgia and ocular zoster, but also causes inflammatory vasculopathy and increases the incidence of hemorrhagic or ischemic complications. Therefore, understanding the association between the development of herpes zoster and the subsequent occurrence of acute stroke or cardiovascular diseases, including myocardial infarction and heart failure, is of great interest. Conversely, many risk factors are involved in the development of herpes zoster. Recently, it has become clear that aging, insufficient immune function, and diseases related to lifestyle habits (for example, stroke and cardiovascular disease), can trigger the onset of herpes zoster. Preventing the onset of herpes zoster, which substantially reduces quality of life, will lead to lower medical costs for countries and extend healthy life expectancy for general populations. Thus, because herpes zoster is a vaccine-preventable disease, active vaccination is recommended for high-risk groups. This review summarizes the association between herpes zoster and cardiovascular disease and vaccination against herpes zoster as a useful disease management and prevention measure for cardiovascular disease. Full article

(This article belongs to the Special Issue Communicable Diseases: New and Old Therapies and Preventive Strategies)

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37 pages, 1601 KiB

Open AccessEditor’s ChoiceReview

Vaccine Strategies to Elicit Mucosal Immunity

by Yufeng Song, Frances Mehl and Steven L. Zeichner

Vaccines 2024, 12(2), 191; https://doi.org/10.3390/vaccines12020191 - 13 Feb 2024

Cited by 27 | Viewed by 10115

Abstract

Vaccines are essential tools to prevent infection and control transmission of infectious diseases that threaten public health. Most infectious agents enter their hosts across mucosal surfaces, which make up key first lines of host defense against pathogens. Mucosal immune responses play critical roles [...] Read more.

Vaccines are essential tools to prevent infection and control transmission of infectious diseases that threaten public health. Most infectious agents enter their hosts across mucosal surfaces, which make up key first lines of host defense against pathogens. Mucosal immune responses play critical roles in host immune defense to provide durable and better recall responses. Substantial attention has been focused on developing effective mucosal vaccines to elicit robust localized and systemic immune responses by administration via mucosal routes. Mucosal vaccines that elicit effective immune responses yield protection superior to parenterally delivered vaccines. Beyond their valuable immunogenicity, mucosal vaccines can be less expensive and easier to administer without a need for injection materials and more highly trained personnel. However, developing effective mucosal vaccines faces many challenges, and much effort has been directed at their development. In this article, we review the history of mucosal vaccine development and present an overview of mucosal compartment biology and the roles that mucosal immunity plays in defending against infection, knowledge that has helped inform mucosal vaccine development. We explore new progress in mucosal vaccine design and optimization and novel approaches created to improve the efficacy and safety of mucosal vaccines. Full article

(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)

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14 pages, 871 KiB

Open AccessEditor’s ChoiceSystematic Review

Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Post-COVID Syndrome: A Systematic Review and Meta-Analysis

by Milena Adina Man, Daniela Rosca, Felix Bratosin, Ovidiu Fira-Mladinescu, Adrian Cosmin Ilie, Sonia-Roxana Burtic, Ariadna Petronela Fildan, Camelia Melania Fizedean, Adelina Maria Jianu, Rodica Anamaria Negrean and Monica Steluta Marc

Vaccines 2024, 12(2), 189; https://doi.org/10.3390/vaccines12020189 - 12 Feb 2024

Cited by 18 | Viewed by 3551

Abstract

This systematic review critically evaluated the impact of a pre-infection COVID-19 vaccination on the incidence and severity of post-COVID-19 syndrome and aimed to assess the potential protective effect across different vaccines and patient demographics. This study hypothesized that vaccination before infection substantially reduces [...] Read more.

This systematic review critically evaluated the impact of a pre-infection COVID-19 vaccination on the incidence and severity of post-COVID-19 syndrome and aimed to assess the potential protective effect across different vaccines and patient demographics. This study hypothesized that vaccination before infection substantially reduces the risk and severity of post-COVID-19 syndrome. In October 2023, a comprehensive literature search was conducted across three databases, PubMed, Embase, and Scopus, focusing on studies published up to that date. Utilizing a wide array of keywords, the search strategy adhered to the PRISMA guidelines and was registered in the Open Science Framework. The inclusion criteria comprised studies focusing on patients with a breakthrough SARS-CoV-2 infection who developed post-COVID-19 syndrome. We included a total of 13 articles that met the inclusion criteria, analyzing more than 10 million patients with a mean age of 50.6 years, showing that the incidence of intensive care unit (ICU) admissions post-vaccination was as low as 2.4%, with a significant reduction in mortality risk (OR 0.66, 95% CI 0.58–0.74). The prevalence of post-COVID-19 syndrome symptoms was lower in vaccinated individuals (9.5%) compared to unvaccinated (14.6%), with a notable decrease in activity-limiting symptoms (adjusted OR 0.59, 95% CI 0.48–0.73). Vaccinated patients also showed a quicker recovery and return to work (HR 1.37, 95% CI 1.04–1.79). The pooled odds ratio of 0.77 indicates that vaccination is associated with a 23% reduction in the risk of developing post-COVID-19 syndrome (95% CI 0.75–0.79). Despite the protective effects observed, a substantial heterogeneity among the studies was noted. In conclusion, a pre-infection COVID-19 vaccination is associated with a significant reduction in the risk and severity of post-COVID-19 syndrome. However, the observed heterogeneity across studies suggests a need for further research with standardized methods to fully comprehend vaccine efficacy against long COVID. Full article

(This article belongs to the Special Issue Acute and Post-acute Sequelae of SARS-CoV-2 Infection: Focus on Systemic Complications)

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17 pages, 2206 KiB

Open AccessEditor’s ChoiceReview

Unveiling the Multifaceted Roles of ISG15: From Immunomodulation to Therapeutic Frontiers

by Enrique Álvarez, Michela Falqui, Laura Sin, Joseph Patrick McGrail, Beatriz Perdiguero, Rocío Coloma, Laura Marcos-Villar, Céline Tárrega, Mariano Esteban, Carmen Elena Gómez and Susana Guerra

Vaccines 2024, 12(2), 153; https://doi.org/10.3390/vaccines12020153 - 1 Feb 2024

Cited by 10 | Viewed by 5701

Abstract

The Interferon Stimulated Gene 15 (ISG15), a unique Ubiquitin-like (Ubl) modifier exclusive to vertebrates, plays a crucial role in the immune system. Primarily induced by interferon (IFN) type I, ISG15 functions through diverse mechanisms: (i) covalent protein modification (ISGylation); (ii) non-covalent intracellular action; [...] Read more.

The Interferon Stimulated Gene 15 (ISG15), a unique Ubiquitin-like (Ubl) modifier exclusive to vertebrates, plays a crucial role in the immune system. Primarily induced by interferon (IFN) type I, ISG15 functions through diverse mechanisms: (i) covalent protein modification (ISGylation); (ii) non-covalent intracellular action; and (iii) exerting extracellular cytokine activity. These various roles highlight its versatility in influencing numerous cellular pathways, encompassing DNA damage response, autophagy, antiviral response, and cancer-related processes, among others. The well-established antiviral effects of ISGylation contrast with its intriguing dual role in cancer, exhibiting both suppressive and promoting effects depending on the tumour type. The multifaceted functions of ISG15 extend beyond intracellular processes to extracellular cytokine signalling, influencing immune response, chemotaxis, and anti-tumour effects. Moreover, ISG15 emerges as a promising adjuvant in vaccine development, enhancing immune responses against viral antigens and demonstrating efficacy in cancer models. As a therapeutic target in cancer treatment, ISG15 exhibits a double-edged nature, promoting or suppressing oncogenesis depending on the tumour context. This review aims to contribute to future studies exploring the role of ISG15 in immune modulation and cancer therapy, potentially paving the way for the development of novel therapeutic interventions, vaccine development, and precision medicine. Full article

(This article belongs to the Special Issue Immunotherapeutics for Treating Infectious Diseases and Beyond)

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38 pages, 1762 KiB

Open AccessEditor’s ChoiceReview

Human Tick-Borne Diseases and Advances in Anti-Tick Vaccine Approaches: A Comprehensive Review

by Marie-Edith Nepveu-Traversy, Hugues Fausther-Bovendo and George (Giorgi) Babuadze

Vaccines 2024, 12(2), 141; https://doi.org/10.3390/vaccines12020141 - 29 Jan 2024

Cited by 22 | Viewed by 10219

Abstract

This comprehensive review explores the field of anti-tick vaccines, addressing their significance in combating tick-borne diseases of public health concern. The main objectives are to provide a brief epidemiology of diseases affecting humans and a thorough understanding of tick biology, traditional tick control [...] Read more.

This comprehensive review explores the field of anti-tick vaccines, addressing their significance in combating tick-borne diseases of public health concern. The main objectives are to provide a brief epidemiology of diseases affecting humans and a thorough understanding of tick biology, traditional tick control methods, the development and mechanisms of anti-tick vaccines, their efficacy in field applications, associated challenges, and future prospects. Tick-borne diseases (TBDs) pose a significant and escalating threat to global health and the livestock industries due to the widespread distribution of ticks and the multitude of pathogens they transmit. Traditional tick control methods, such as acaricides and repellents, have limitations, including environmental concerns and the emergence of tick resistance. Anti-tick vaccines offer a promising alternative by targeting specific tick proteins crucial for feeding and pathogen transmission. Developing vaccines with antigens based on these essential proteins is likely to disrupt these processes. Indeed, anti-tick vaccines have shown efficacy in laboratory and field trials successfully implemented in livestock, reducing the prevalence of TBDs. However, some challenges still remain, including vaccine efficacy on different hosts, polymorphisms in ticks of the same species, and the economic considerations of adopting large-scale vaccine strategies. Emerging technologies and approaches hold promise for improving anti-tick vaccine development and expanding their impact on public health and agriculture. Full article

(This article belongs to the Special Issue Vaccines against Emerging Infectious Diseases)

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28 pages, 3220 KiB

Open AccessEditor’s ChoiceReview

Advances in Poultry Vaccines: Leveraging Biotechnology for Improving Vaccine Development, Stability, and Delivery

by Khaled Abdelaziz, Yosra A. Helmy, Alexander Yitbarek, Douglas C. Hodgins, Tamer A. Sharafeldin and Mohamed S. H. Selim

Vaccines 2024, 12(2), 134; https://doi.org/10.3390/vaccines12020134 - 28 Jan 2024

Cited by 13 | Viewed by 13341

Abstract

With the rapidly increasing demand for poultry products and the current challenges facing the poultry industry, the application of biotechnology to enhance poultry production has gained growing significance. Biotechnology encompasses all forms of technology that can be harnessed to improve poultry health and [...] Read more.

With the rapidly increasing demand for poultry products and the current challenges facing the poultry industry, the application of biotechnology to enhance poultry production has gained growing significance. Biotechnology encompasses all forms of technology that can be harnessed to improve poultry health and production efficiency. Notably, biotechnology-based approaches have fueled rapid advances in biological research, including (a) genetic manipulation in poultry breeding to improve the growth and egg production traits and disease resistance, (b) rapid identification of infectious agents using DNA-based approaches, (c) inclusion of natural and synthetic feed additives to poultry diets to enhance their nutritional value and maximize feed utilization by birds, and (d) production of biological products such as vaccines and various types of immunostimulants to increase the defensive activity of the immune system against pathogenic infection. Indeed, managing both existing and newly emerging infectious diseases presents a challenge for poultry production. However, recent strides in vaccine technology are demonstrating significant promise for disease prevention and control. This review focuses on the evolving applications of biotechnology aimed at enhancing vaccine immunogenicity, efficacy, stability, and delivery. Full article

(This article belongs to the Special Issue Virus-Like Particle (VLP) Vaccines against Emerging Infectious Diseases)

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27 pages, 2498 KiB

Open AccessEditor’s ChoiceReview

All Eyes on the Prefusion-Stabilized F Construct, but Are We Missing the Potential of Alternative Targets for Respiratory Syncytial Virus Vaccine Design?

by Sofie Schaerlaekens, Lotte Jacobs, Kim Stobbelaar, Paul Cos and Peter Delputte

Vaccines 2024, 12(1), 97; https://doi.org/10.3390/vaccines12010097 - 18 Jan 2024

Cited by 17 | Viewed by 8120

Abstract

Respiratory Syncytial Virus (RSV) poses a significant global health concern as a major cause of lower respiratory tract infections (LRTIs). Over the last few years, substantial efforts have been directed towards developing vaccines and therapeutics to combat RSV, leading to a diverse landscape [...] Read more.

Respiratory Syncytial Virus (RSV) poses a significant global health concern as a major cause of lower respiratory tract infections (LRTIs). Over the last few years, substantial efforts have been directed towards developing vaccines and therapeutics to combat RSV, leading to a diverse landscape of vaccine candidates. Notably, two vaccines targeting the elderly and the first maternal vaccine have recently been approved. The majority of the vaccines and vaccine candidates rely solely on a prefusion-stabilized conformation known for its highly neutralizing epitopes. Although, so far, this antigen design appears to be successful for the elderly, our current understanding remains incomplete, requiring further improvement and refinement in this field. Pediatric vaccines still have a long journey ahead, and we must ensure that vaccines currently entering the market do not lose efficacy due to the emergence of mutations in RSV’s circulating strains. This review will provide an overview of the current status of vaccine designs and what to focus on in the future. Further research into antigen design is essential, including the exploration of the potential of alternative RSV proteins to address these challenges and pave the way for the development of novel and effective vaccines, especially in the pediatric population. Full article

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13 pages, 234 KiB

Open AccessEditor’s ChoiceArticle

Prevalence and Factors Associated with Long COVID Symptoms among U.S. Adults, 2022

by Kimberly H. Nguyen, Yingjun Bao, Julie Mortazavi, Jennifer D. Allen, Patricia O. Chocano-Bedoya and Laura Corlin

Vaccines 2024, 12(1), 99; https://doi.org/10.3390/vaccines12010099 - 18 Jan 2024

Cited by 16 | Viewed by 3326

Abstract

Long COVID and its symptoms have not been examined in different subpopulations of U.S. adults. Using the 2022 BRFSS (n = 445,132), we assessed long COVID and each symptom by sociodemographic characteristics and health-related variables. Multivariable logistic regression was conducted to examine factors [...] Read more.

Long COVID and its symptoms have not been examined in different subpopulations of U.S. adults. Using the 2022 BRFSS (n = 445,132), we assessed long COVID and each symptom by sociodemographic characteristics and health-related variables. Multivariable logistic regression was conducted to examine factors associated with long COVID and the individual symptoms. Prevalence differences were conducted to examine differences in long COVID by vaccination status. Overall, more than one in five adults who ever had COVID-19 reported symptoms consistent with long COVID (21.8%). The most common symptom was tiredness or fatigue (26.2%), followed by difficulty breathing or shortness of breath (18.9%), and loss of taste or smell (17.0%). Long COVID was more common among adults under 65 years, women, American Indian or Alaska Native or other/multi race group, smokers, and people with a disability, depression, overweight or obesity compared to their respective counterparts. The prevalence of long COVID was higher among unvaccinated adults (25.6%) than vaccinated adults (21.6%) overall, and for 20 of 32 subgroups assessed. These findings underscore the benefits of vaccination, the importance of early treatment, and the need to better inform health care resource allocation and support services for those experiencing long COVID. Full article

(This article belongs to the Special Issue Infectious Diseases: Importance for Public Health, Epidemiology, Promoting Factors, and Vaccines Prevention)

23 pages, 3279 KiB

Open AccessEditor’s ChoiceReview

DNA Vaccines: Their Formulations, Engineering and Delivery

by Michael Kozak and Jiafen Hu

Vaccines 2024, 12(1), 71; https://doi.org/10.3390/vaccines12010071 - 11 Jan 2024

Cited by 41 | Viewed by 10258

Abstract

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements in the augmentation of the immunogenicity of DNA vaccines have brought this technology to the market, especially in veterinary medicine, to prevent many diseases. Along with the successful COVID [...] Read more.

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements in the augmentation of the immunogenicity of DNA vaccines have brought this technology to the market, especially in veterinary medicine, to prevent many diseases. Along with the successful COVID mRNA vaccines, the first DNA vaccine for human use, the Indian ZyCovD vaccine against SARS-CoV-2, was approved in 2021. In the current review, we first give an overview of the DNA vaccine focusing on the science, including adjuvants and delivery methods. We then cover some of the emerging science in the field of DNA vaccines, notably efforts to optimize delivery systems, better engineer delivery apparatuses, identify optimal delivery sites, personalize cancer immunotherapy through DNA vaccination, enhance adjuvant science through gene adjuvants, enhance off-target and heritable immunity through epigenetic modification, and predict epitopes with bioinformatic approaches. We also discuss the major limitations of DNA vaccines and we aim to address many theoretical concerns. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

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17 pages, 2701 KiB

Open AccessEditor’s ChoiceArticle

Centrosomal Protein 55 (CEP55) Drives Immune Exclusion and Resistance to Immune Checkpoint Inhibitors in Colorectal Cancer

by Dechen Wangmo, Travis J. Gates, Xianda Zhao, Ruping Sun and Subbaya Subramanian

Vaccines 2024, 12(1), 63; https://doi.org/10.3390/vaccines12010063 - 8 Jan 2024

Cited by 6 | Viewed by 2988

Abstract

Colorectal cancer (CRC) currently ranks as the third most common cancer in the United States, and its incidence is on the rise, especially among younger individuals. Despite the remarkable success of immune checkpoint inhibitors (ICIs) in various cancers, most CRC patients fail to [...] Read more.

Colorectal cancer (CRC) currently ranks as the third most common cancer in the United States, and its incidence is on the rise, especially among younger individuals. Despite the remarkable success of immune checkpoint inhibitors (ICIs) in various cancers, most CRC patients fail to respond due to intrinsic resistance mechanisms. While microsatellite instability-high phenotypes serve as a reliable positive predictive biomarker for ICI treatment, the majority of CRC patients with microsatellite-stable (MSS) tumors remain ineligible for this therapeutic approach. In this study, we investigated the role of centrosomal protein 55 (CEP55) in shaping the tumor immune microenvironment in CRC. CEP55 is overexpressed in multiple cancer types and was shown to promote tumorigenesis by upregulating the PI3K/AKT pathway. Our data revealed that elevated CEP55 expression in CRC was associated with reduced T cell infiltration, contributing to immune exclusion. As CRC tumors progressed, CEP55 expression increased alongside sequential mutations in crucial driver genes (APC, KRAS, TP53, and SMAD4), indicating its involvement in tumor progression. CEP55 knockout significantly impaired tumor growth in vitro and in vivo, suggesting that CEP55 plays a crucial role in tumorigenesis. Furthermore, the CEP55 knockout increased CD8⁺ T cell infiltration and granzyme B production, indicating improved anti-tumor immunity. Additionally, we observed reduced regulatory T cell infiltration in CEP55 knockout tumors, suggesting diminished immune suppression. Most significantly, CEP55 knockout tumors demonstrated enhanced responsiveness to immune checkpoint inhibition in a clinically relevant orthotopic CRC model. Treatment with anti-PD1 significantly reduced tumor growth in CEP55 knockout tumors compared to control tumors, suggesting that inhibiting CEP55 could improve the efficacy of ICIs. Collectively, our study underscores the crucial role of CEP55 in driving immune exclusion and resistance to ICIs in CRC. Targeting CEP55 emerges as a promising therapeutic strategy to sensitize CRC to immune checkpoint inhibition, thereby improving survival outcomes for CRC patients. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

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11 pages, 249 KiB

Open AccessEditor’s ChoiceArticle

Herpes Zoster Vaccine Uptake and Active Campaign Impact, a Multicenter Retrospective Study in Italy

by Andrea Ceccarelli, Federica Tamarri, Raffaella Angelini, Elizabeth Bakken, Ilaria Concari, Elsa Giannoccaro, Giada Domeniconi, Michela Morri, Chiara Reali, Francesca Righi, Silvia Serra, Gianmaria Semprini, Giulia Silvestrini, Valentina Turri, Davide Gori and Marco Montalti

Vaccines 2024, 12(1), 51; https://doi.org/10.3390/vaccines12010051 - 3 Jan 2024

Cited by 8 | Viewed by 2633

Abstract

The Herpes Zoster (HZ) vaccination has proven both safe and effective in alleviating conditions related to HZ, leading to significant cost savings in national healthcare and social systems. In Italy, it is recommended and provided free of charge to individuals aged 65 and [...] Read more.

The Herpes Zoster (HZ) vaccination has proven both safe and effective in alleviating conditions related to HZ, leading to significant cost savings in national healthcare and social systems. In Italy, it is recommended and provided free of charge to individuals aged 65 and older. To achieve broad vaccination coverage, alongside ordinary immunization campaigns, active and catch-up campaigns were implemented. This retrospective observational study aimed to observe the vaccination coverage achieved in the Romagna Local Health Authority (LHA) during the 2023 active campaign, with a secondary goal of assessing the impact of the 2022 catch-up campaign and the 2023 active campaign compared to ordinary campaigns. As of 3 July 2023, an overall vaccine uptake of 13.5% was achieved among individuals born in 1958, with variations among the four LHA centers ranging from 10.2% to 17.7%. Catch-up and active campaigns together contributed to nearly half of the achieved coverage in Center No. 1 and a quarter in Center No. 2. Notably, individuals born in 1957, not included in the Center No. 2 catch-up campaign, reached significantly lower vaccination coverage compared to other cohorts and centers. Analyzing the use of text messages for active campaigns, it was observed that cohort groups did not show substantial differences in text-message utilization for warnings. However, having relatives who had experienced HZ-related symptoms significantly reduced the reliance on text messages as warnings. These results highlighted how catch-up and active campaigns effectively increased vaccine coverage. Nevertheless, differences in uptake among different centers within the same LHA and the limited contribution of other information sources compared to text messages suggest the necessity of designing campaigns involving all available channels and stakeholders to maximize vaccine uptake. Full article

(This article belongs to the Section Epidemiology and Vaccination)

12 pages, 2101 KiB

Open AccessEditor’s ChoiceArticle

Cemiplimab in Ultra-Octogenarian Patients with Cutaneous Squamous Cell Carcinoma: The Real-Life Experience of a Tertiary Referral Center

by Nerina Denaro, Emanuela Passoni, Alice Indini, Gianluca Nazzaro, Giada Anna Beltramini, Valentina Benzecry, Giuseppe Colombo, Carolina Cauchi, Cinzia Solinas, Mario Scartozzi, Angelo Valerio Marzano and Ornella Garrone

Vaccines 2023, 11(9), 1500; https://doi.org/10.3390/vaccines11091500 - 18 Sep 2023

Cited by 4 | Viewed by 2353

Abstract

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, paralleling the aging of the population. cSCC predominantly affects chronically sun-exposed areas, such as the head and neck region. At our tertiary center, a multidisciplinary approach to non-melanoma skin cancer is [...] Read more.

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, paralleling the aging of the population. cSCC predominantly affects chronically sun-exposed areas, such as the head and neck region. At our tertiary center, a multidisciplinary approach to non-melanoma skin cancer is provided for locally advanced cSCC. Methods: We retrospectively revised all patients with locally advanced/metastatic cSCC treated with anti-PD1 antibody (Cemiplimab) at our Institution from January 2020 to March 2023 (minimum follow-up of 4 months on treatment). Results: Overall, we consecutively treated 20 ultra-octogenarian patients, of whom 15 were males and 5 were females (median age: 86.9 years). Despite age, a median number of concomitant drugs, and comorbidities, efficacy, and safety were superimposable with the available literature. No patients reported treatment-related adverse events of grade 3 or higher. Grade 2 adverse events were reported in 25% of patients. Overall, the response rate was 65%, with 50% partial responses and 20% long-lasting stable disease. The median duration of response was 14 months. The G8 elderly score was assessed in all patients, and the median score was 12 (range 9–14). Conclusions: Among ultra-octogenarian patients, a clinical benefit from Cemiplimab was obtained in most, including tumor shrinkage and pain relief. Cemiplimab confirmed its effectiveness in elderly patients in a real-life setting, with no new safety concerns. Full article

(This article belongs to the Special Issue Tumor Vaccine Development, Immune-Based Therapies and Immune Markers)

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16 pages, 318 KiB

Open AccessEditor’s ChoiceReview

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma

by Alireza Tojjari, Ahmed Saeed, Meghana Singh, Ludimila Cavalcante, Ibrahim Halil Sahin and Anwaar Saeed

Vaccines 2023, 11(8), 1357; https://doi.org/10.3390/vaccines11081357 - 12 Aug 2023

Cited by 27 | Viewed by 5710

Abstract

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the [...] Read more.

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the significance of personalized therapies, innovative antigen delivery platforms, immune modulatory agents, and predictive biomarkers in revolutionizing HCC treatment. Simple Summary: This review explores the potential of cancer vaccines as a promising therapeutic strategy for hepatocellular carcinoma (HCC), a prevalent and deadly liver cancer. The authors discuss various types of cancer vaccines, their challenges, and their role in modulating the immune response within HCC. They also highlight clinical trials and future perspectives, emphasizing the importance of personalized therapies, novel antigen delivery platforms, and predictive biomarkers. The findings from this research could significantly impact the research community by providing a comprehensive understanding of the current state of cancer vaccines for HCC, thereby guiding future research and potentially transforming HCC treatment strategies. Full article

(This article belongs to the Special Issue Cancer Vaccines 3.0)

13 pages, 797 KiB

Open AccessEditor’s ChoiceArticle

Changes in Confidence, Feelings, and Perceived Necessity Concerning COVID-19 Booster

by Cheryl Lin, Brooke Bier, Ann M. Reed, John J. Paat and Pikuei Tu

Vaccines 2023, 11(7), 1244; https://doi.org/10.3390/vaccines11071244 - 15 Jul 2023

Cited by 8 | Viewed by 2625

Abstract

The COVID-19 booster first became available to all adults in the U.S. in November 2021 and a bivalent version in September 2022, but a large population remains booster-hesitant; only 17% of Americans have obtained the updated vaccine as of June 2023. We conducted [...] Read more.

The COVID-19 booster first became available to all adults in the U.S. in November 2021 and a bivalent version in September 2022, but a large population remains booster-hesitant; only 17% of Americans have obtained the updated vaccine as of June 2023. We conducted two cross-sectional surveys in 2021 and 2022 (n = 1889 and 1319) to determine whether changes in booster-related feelings or perceptions had occurred and whether they altered vaccination rates over time. We found that both positive and negative emotions had grown stronger between the two years, with the prevalence of annoyance increasing the most (21.5% to 39.7%). The impact of trust on booster intention more than doubled (OR = 7.46 to 16.04). Although perceived risk of infection decreased, more participants in 2022 indicated uncertainty or unwillingness to obtain a new booster than in 2021, while the proportion refusing a booster remained constant at 22.5%. Confidence in the COVID-19 vaccine and feelings of hope from the booster motivated acceptance; both were stronger predictors of booster receptivity than prior vaccination history. Our findings signal a need to rebuild trust by informing people of their continued risk and appealing to positive, especially optimistic emotions to encourage booster uptake. Future research should explore longitudinal trends in behavior and feelings toward new booster doses and the impact of prolonged vaccine hesitancy on infection rates. Full article

(This article belongs to the Special Issue Vaccine Hesitancy and Acceptance, Trends and Future Prospects for Public Health)

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12 pages, 286 KiB

Open AccessEditor’s ChoiceArticle

A Parent Version of the Motors of COVID-19 Vaccination Acceptance Scale for Assessing Parents’ Motivation to Have Their Children Vaccinated

by Chung-Ying Lin, Ray C. Hsiao, Yu-Min Chen and Cheng-Fang Yen

Vaccines 2023, 11(7), 1192; https://doi.org/10.3390/vaccines11071192 - 3 Jul 2023

Cited by 9 | Viewed by 2868

Abstract

Parents’ motivation to vaccinate their children against coronavirus disease 2019 (COVID-19) plays a crucial role in the uptake of COVID-19 vaccines among children. The Motors of COVID-19 Vaccination Acceptance Scale (MoVac-COVID19S) is a valuable tool for assessing individuals’ vaccination-related attitudes and the factors [...] Read more.

Parents’ motivation to vaccinate their children against coronavirus disease 2019 (COVID-19) plays a crucial role in the uptake of COVID-19 vaccines among children. The Motors of COVID-19 Vaccination Acceptance Scale (MoVac-COVID19S) is a valuable tool for assessing individuals’ vaccination-related attitudes and the factors influencing their decision to be vaccinated against COVID-19. This study adapted the MoVac-COVID19S to create a parent version (P-MoVac-COVID19S) and examined the psychometric soundness of two P-MoVac-COVID19S versions (a 9-item version (P-MoVac-COVID19S-9) and a 12-item version (P-MoVac-COVID19S-12)) for assessing parents’ motivation to vaccinate their children. A total of 550 parents completed the P-MoVac-COVID19S and a questionnaire assessing the factors that impact parents’ intention to allow their children to receive the COVID-19 vaccine using a vaccine acceptance scale. We enquired about the level of parental worry regarding the adverse effects of COVID-19 vaccines on children’s health and the number of COVID-19 vaccine doses received by parents. The factor structures of the P-MoVac-COVID19S-9 and P-MoVac-COVID19S-12 were examined using confirmatory factor analysis. The internal consistency, test–retest reliability, and concurrent validity of the P-MoVac-COVID19S were also examined. The results revealed that the P-MoVac-COVID19S-12 has a four-factor structure, which aligns well with the theoretical framework of the cognitive model of empowerment; the P-MoVac-COVID19S-9 has a one-factor structure. Both the P-MoVac-COVID19S-9 and P-MoVac-COVID19S-12 had good internal consistency and test–retest reliability and acceptable concurrent validity. The results of this study demonstrated that the P-MoVac-COVID19S is a reliable and valid instrument for assessing parent’s motivation to vaccinate their children against COVID-19. Full article

(This article belongs to the Special Issue Vaccine Hesitancy)

9 pages, 249 KiB

Open AccessEditor’s ChoiceArticle

Attitudes and Beliefs towards Rotavirus Vaccination in a Sample of Italian Women: A Cross-Sectional Study

by Giuseppe Di Martino, Riccardo Mazzocca, Laura Camplone, Fabrizio Cedrone, Pamela Di Giovanni and Tommaso Staniscia

Vaccines 2023, 11(6), 1041; https://doi.org/10.3390/vaccines11061041 - 30 May 2023

Cited by 4 | Viewed by 4413

Abstract

(1) Background: Rotavirus is the leading cause of severe diarrhea and dehydration in infants and young children worldwide. Despite the proven benefits of vaccination, vaccine hesitancy and refusal remains a significant barrier to achieving high vaccination coverage in many countries, such as Italy. [...] Read more.

(1) Background: Rotavirus is the leading cause of severe diarrhea and dehydration in infants and young children worldwide. Despite the proven benefits of vaccination, vaccine hesitancy and refusal remains a significant barrier to achieving high vaccination coverage in many countries, such as Italy. (2) Methods: An online survey was conducted among women aged between 18 and 50 years from Abruzzo Region, Italy. The survey was composed of two main sections: demographic characteristics and attitudes and knowledge about rotavirus vaccination, based on a five-point Likert scale. Logistic regression analysis was performed to evaluate factors associated with willingness to get the rotavirus vaccination. (3) Results: A total of 414 women were enrolled in the study. Women who were unaware of rotavirus more frequently had a lower education level (university degree 62.5% vs. 78.7%, p = 0.004) and reported having no children (p < 0.001). About half of the enrolled women thought that rotavirus infection is dangerous (190, 55.6%) and that rotavirus can cause a serious illness (201, 58.8%). Regarding associated factors, women informed by a physician were more likely get a vaccination compared to women informed by friends or relatives (OR 34.35, 95% CI 7.12–98.98, p < 0.001). (4) Conclusions: The present study showed low levels of knowledge and attitudes towards rotavirus vaccination. These results highlight the need for developing and improving additional public education programs for parents. Full article

(This article belongs to the Special Issue Recent Advances in Factors Associated with Vaccine Hesitancy and Acceptance)

12 pages, 2790 KiB

Open AccessEditor’s ChoiceArticle

Comparison of the Immune Effects of an mRNA Vaccine and a Subunit Vaccine against Herpes Zoster Administered by Different Injection Methods

by Kangyang Lin, Han Cao, Ning Luan, Yunfei Wang, Jingping Hu and Cunbao Liu

Vaccines 2023, 11(5), 1003; https://doi.org/10.3390/vaccines11051003 - 20 May 2023

Cited by 9 | Viewed by 4298

Abstract

Previous studies have shown that the herpes zoster subunit vaccine Shingrix™ performs well in clinical trials. However, the key ingredient in its adjuvant, QS21, is extracted from rare plants in South America, so vaccine production is limited. Compared with subunit vaccines, mRNA vaccines [...] Read more.

Previous studies have shown that the herpes zoster subunit vaccine Shingrix™ performs well in clinical trials. However, the key ingredient in its adjuvant, QS21, is extracted from rare plants in South America, so vaccine production is limited. Compared with subunit vaccines, mRNA vaccines have the advantages of faster production and not requiring adjuvants, but currently, there is no authorized mRNA vaccine for herpes zoster. Therefore, this study focused on herpes zoster subunit and mRNA vaccines. We prepared a herpes zoster mRNA vaccine and compared the effects of vaccine type, immunization route, and adjuvant use on vaccine immunological efficacy. The mRNA vaccine was injected directly into mice via subcutaneous or intramuscular injection. The subunit vaccine was mixed with adjuvants before immunization. The adjuvants include B2Q or alum. B2Q is BW006S + 2395S + QS21. BW006S and 2395S are phosphodiester CpG oligodeoxynucleotides (CpG ODNs). Then, we compared the cell-mediated immunity (CIM) and humoral immunity levels of the different groups of mice. The results showed that the immune responses of mice inoculated with the mRNA vaccine prepared in this study were not significantly different from those of mice inoculated with the protein subunit vaccine supplemented with the B2Q. The mRNA vaccine-induced immune responses following subcutaneous or intramuscular injection, and the different immunization routes did not lead to significant differences in immune response intensity. Similar results were also observed for the protein subunit vaccine adjuvanted with B2Q but not alum. The above results suggest that our experiment can provide a reference for the preparation of mRNA vaccines against herpes zoster and has certain reference significance for the selection of the immunization route; that is, there is no significant difference in the immune response caused by subcutaneous versus an intramuscular injection, so the injection route can be determined according to the actual situation of individuals. Full article

(This article belongs to the Special Issue Cellular Immune Responses to Infectious Diseases)

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13 pages, 1334 KiB

Open AccessEditor’s ChoiceArticle

Predicted Public Health and Economic Impact of Respiratory Syncytial Virus Vaccination with Variable Duration of Protection for Adults ≥60 Years in Belgium

by Maarten J. Postma, Chih-Yuan Cheng, Nasuh C. Buyukkaramikli, Luis Hernandez Pastor, Ine Vandersmissen, Thierry Van Effelterre, Peter Openshaw and Steven Simoens

Vaccines 2023, 11(5), 990; https://doi.org/10.3390/vaccines11050990 - 16 May 2023

Cited by 8 | Viewed by 5150

Abstract

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection (ARI) in older adults. This study used a static, cohort-based decision-tree model to estimate the public health and economic impact of vaccination against RSV in Belgians aged ≥60 years compared with [...] Read more.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection (ARI) in older adults. This study used a static, cohort-based decision-tree model to estimate the public health and economic impact of vaccination against RSV in Belgians aged ≥60 years compared with no vaccination for different vaccine duration of protection profiles from a healthcare payer perspective. Three vaccine protection durations were compared (1, 3, and 5 years), and several sensitivity and scenario analyses were performed. Results showed that an RSV vaccine with a 3-year duration of protection would prevent 154,728 symptomatic RSV-ARI cases, 3688 hospitalizations, and 502 deaths over three years compared to no vaccination in older adults and would save EUR 35,982,857 in direct medical costs in Belgium. The number needed to vaccinate to prevent one RSV-ARI case was 11 for the 3-year duration profile, while it was 28 and 8 for the 1- and 5-year vaccine duration profiles, respectively. The model was generally robust in sensitivity analyses varying key input values. This study suggested that vaccination could substantially decrease the public health and economic burden of RSV in adults ≥60 years in Belgium, with benefits increasing with a longer duration of vaccine protection. Full article

(This article belongs to the Section Vaccines and Public Health)

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12 pages, 1507 KiB

Open AccessEditor’s ChoiceArticle

Validation of an HPLC-CAD Method for Determination of Lipid Content in LNP-Encapsulated COVID-19 mRNA Vaccines

by Xiaojuan Yu, Chuanfei Yu, Xiaohong Wu, Yu Cui, Xiaoda Liu, Yan Jin, Yuhua Li and Lan Wang

Vaccines 2023, 11(5), 937; https://doi.org/10.3390/vaccines11050937 - 4 May 2023

Cited by 12 | Viewed by 8719

Abstract

Lipid nanoparticles (LNPs) are widely used as delivery systems for mRNA vaccines. The stability and bilayer fluidity of LNPs are determined by the properties and contents of the various lipids used in the formulation system, and the delivery efficiency of LNPs largely depends [...] Read more.

Lipid nanoparticles (LNPs) are widely used as delivery systems for mRNA vaccines. The stability and bilayer fluidity of LNPs are determined by the properties and contents of the various lipids used in the formulation system, and the delivery efficiency of LNPs largely depends on the lipid composition. For the quality control of such vaccines, here we developed and validated an HPLC-CAD method to identify and determine the contents of four lipids in an LNP-encapsulated COVID-19 mRNA vaccine to support lipid analysis for the development of new drugs and vaccines. Full article

(This article belongs to the Special Issue Vaccines or Immunotherapy for Viruses)

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28 pages, 1360 KiB

Open AccessEditor’s ChoiceReview

Engineered Phage-Based Cancer Vaccines: Current Advances and Future Directions

by Murali Ragothaman and So Young Yoo

Vaccines 2023, 11(5), 919; https://doi.org/10.3390/vaccines11050919 - 29 Apr 2023

Cited by 32 | Viewed by 7681

Abstract

Bacteriophages have emerged as versatile tools in the field of bioengineering, with enormous potential in tissue engineering, vaccine development, and immunotherapy. The genetic makeup of phages can be harnessed for the development of novel DNA vaccines and antigen display systems, as they can [...] Read more.

Bacteriophages have emerged as versatile tools in the field of bioengineering, with enormous potential in tissue engineering, vaccine development, and immunotherapy. The genetic makeup of phages can be harnessed for the development of novel DNA vaccines and antigen display systems, as they can provide a highly organized and repetitive presentation of antigens to immune cells. Bacteriophages have opened new possibilities for the targeting of specific molecular determinants of cancer cells. Phages can be used as anticancer agents and carriers of imaging molecules and therapeutics. In this review, we explored the role of bacteriophages and bacteriophage engineering in targeted cancer therapy. The question of how the engineered bacteriophages can interact with the biological and immunological systems is emphasized to comprehend the underlying mechanism of phage use in cancer immunotherapy. The effectiveness of phage display technology in identifying high-affinity ligands for substrates, such as cancer cells and tumor-associated molecules, and the emerging field of phage engineering and its potential in the development of effective cancer treatments are discussed. We also highlight phage usage in clinical trials as well as the related patents. This review provides a new insight into engineered phage-based cancer vaccines. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

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19 pages, 883 KiB

Open AccessEditor’s ChoiceReview

T Cell Based Immunotherapy for Cancer: Approaches and Strategies

by Muzamil Y. Want, Zeenat Bashir and Rauf A. Najar

Vaccines 2023, 11(4), 835; https://doi.org/10.3390/vaccines11040835 - 13 Apr 2023

Cited by 36 | Viewed by 5719

Abstract

T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved [...] Read more.

T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved through the identification of mutated or overexpressed self-proteins in cancer cells, which guide the recognition of cancer cells by T-cell receptors. There are two main approaches to T cell-based immunotherapy: HLA-restricted and HLA-non-restricted Immunotherapy. Significant progress has been made in T cell-based immunotherapy over the past decade, using naturally occurring or genetically engineered T cells to target cancer antigens in hematological malignancies and solid tumors. However, limited specificity, longevity, and toxicity have limited success rates. This review provides an overview of T cells as a therapeutic tool for cancer, highlighting the advantages and future strategies for developing effective T cell cancer immunotherapy. The challenges associated with identifying T cells and their corresponding antigens, such as their low frequency, are also discussed. The review further examines the current state of T cell-based immunotherapy and potential future strategies, such as the use of combination therapy and the optimization of T cell properties, to overcome current limitations and improve clinical outcomes. Full article

(This article belongs to the Special Issue Immunology and Immunotherapy in Cancer)

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13 pages, 1389 KiB

Open AccessEditor’s ChoiceArticle

Third BNT162b2 mRNA SARS-CoV-2 Vaccine Dose Significantly Enhances Immunogenicity in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

by Israel Henig, Jonathan Isenberg, Dana Yehudai-Ofir, Ronit Leiba, Shimrit Ringelstein-Harlev, Ron Ram, Batia Avni, Odelia Amit, Sigal Grisariu, Tehila Azoulay, Ilana Slouzkey and Tsila Zuckerman

Vaccines 2023, 11(4), 775; https://doi.org/10.3390/vaccines11040775 - 31 Mar 2023

Cited by 6 | Viewed by 3506

Abstract

COVID-19-related mortality among hematopoietic stem cell transplantation (HSCT) recipients in the pre-vaccine era ranged between 22 and 33%. The Pfizer/BioNTech BNT162b2 vaccine demonstrated significant immunogenicity and efficacy in the healthy population; however, its long-term effects on allogeneic HSCT recipients remained unclear. Our study [...] Read more.

COVID-19-related mortality among hematopoietic stem cell transplantation (HSCT) recipients in the pre-vaccine era ranged between 22 and 33%. The Pfizer/BioNTech BNT162b2 vaccine demonstrated significant immunogenicity and efficacy in the healthy population; however, its long-term effects on allogeneic HSCT recipients remained unclear. Our study longitudinally evaluated humoral and cellular responses to the BNT162b2 vaccine in adult allogeneic HSCT patients. A positive response was defined as antibody titers ≥ 150 AU/mL post-second vaccination. Among 77 included patients, 51 (66.2%) responded to vaccination. Response-associated factors were female gender, recent anti-CD20 therapy, and a longer interval between transplant and vaccination. Response rates reached 83.7% in patients vaccinated >12 months post-transplant. At 6 months post-second vaccination, antibody titers dropped, but were significantly increased with the booster dose. Moreover, 43% (6/14) of non-responders to the second vaccination acquired sufficient antibody titers after booster administration, resulting in an overall response rate of 79.5% for the entire cohort. The BNT162b2 vaccine was effective in allogeneic transplant recipients. Although antibody titers decreased with time, the third vaccination led to their significant elevation, with 93% of third-dose responders maintaining titers above 150 AU/mL at 3 months post-administration. Full article

(This article belongs to the Special Issue Safety and Immunogenicity of the COVID-19 Vaccine)

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26 pages, 749 KiB

Open AccessEditor’s ChoiceReview

Anti-HERV-K Drugs and Vaccines, Possible Therapies against Tumors

by Sepideh Hosseiniporgham and Leonardo Antonio Sechi

Vaccines 2023, 11(4), 751; https://doi.org/10.3390/vaccines11040751 - 28 Mar 2023

Cited by 10 | Viewed by 5824

Abstract

The footprint of human endogenous retroviruses (HERV), specifically HERV-K, has been found in malignancies, such as melanoma, teratocarcinoma, osteosarcoma, breast cancer, lymphoma, and ovary and prostate cancers. HERV-K is characterized as the most biologically active HERV due to possession of open reading frames [...] Read more.

The footprint of human endogenous retroviruses (HERV), specifically HERV-K, has been found in malignancies, such as melanoma, teratocarcinoma, osteosarcoma, breast cancer, lymphoma, and ovary and prostate cancers. HERV-K is characterized as the most biologically active HERV due to possession of open reading frames (ORF) for all Gag, Pol, and Env genes, which enables it to be more infective and obstructive towards specific cell lines and other exogenous viruses, respectively. Some factors might contribute to carcinogenicity and at least one of them has been recognized in various tumors, including overexpression/methylation of long interspersed nuclear element 1 (LINE-1), HERV-K Gag, and Env genes themselves plus their transcripts and protein products, and HERV-K reverse transcriptase (RT). Therapies effective for HERV-K-associated tumors mostly target invasive autoimmune responses or growth of tumors through suppression of HERV-K Gag or Env protein and RT. To design new therapeutic options, more studies are needed to better understand whether HERV-K and its products (Gag/Env transcripts and HERV-K proteins/RT) are the initiators of tumor formation or just the disorder’s developers. Accordingly, this review aims to present evidence that highlights the association between HERV-K and tumorigenicity and introduces some of the available or potential therapies against HERV-K-induced tumors. Full article

(This article belongs to the Special Issue State of the Art and Future Directions of Synthetic Biology-Armed Vaccine Development)

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17 pages, 4655 KiB

Open AccessEditor’s ChoiceArticle

Heterologous Vector—mRNA Based SARS-CoV-2 Vaccination Strategy Appears Superior to a Homologous Vector—Based Vaccination Scheme in German Healthcare Workers Regarding Humoral SARS-CoV-2 Response Indicating a High Boosting Effect by mRNA Vaccines

by Catharina Gerhards, Margot Thiaucourt, Michael Hetjens, Verena Haselmann, Michael Neumaier and Maximilian Kittel

Vaccines 2023, 11(3), 701; https://doi.org/10.3390/vaccines11030701 - 19 Mar 2023

Cited by 6 | Viewed by 3383

Abstract

Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector–vector versus heterologous, vector–mRNA), the influence of vaccination side effects, and the infection rate in German healthcare [...] Read more.

Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector–vector versus heterologous, vector–mRNA), the influence of vaccination side effects, and the infection rate in German healthcare workers need to be investigated. Methods: In this study, 103 individuals vaccinated against SARS-CoV-2 were enrolled to examine their anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig levels. A total of 415 blood samples in lithium heparin tubes were prospectively obtained, and a structured survey regarding medical history, type of vaccine, and vaccination reactions was conducted. Results: All participants demonstrated a humoral immune response, among whom no values decreased below the positivity cutoff. Five to six months after the third vaccination, three participants showed anti-RBD/S1 antibodies of less than 1000 U/mL. We observed higher levels for heterologous mRNA-/vector-based combinations compared to pure vector-based vaccination after the second vaccination, which is harmonized after a third vaccination with the mRNA-vaccine only in both cohorts. The incidence of vaccine breakthrough in a highly exposed cohort was 60.3%. Conclusion: Sustained long-term humoral immunity was observed, indicating the superiority of a heterologous mRNA-/vector-based combination compared to pure vector-based vaccination. There was longevity of anti-RBD/S1 antibodies of at least 4 and up to 7 months without external stimulus. Regarding vaccination reactogenity, the occurrence of local symptoms as pain at the injection site was increased after the first mRNA application compared to the vector–vector cohort with a general decrease in adverse events at later vaccination time points. Overall, a correlation between the humoral vaccination response and vaccination side effects was not observed. Despite the high prevalence of vaccine breakthroughs, these only occurred in the later course of the study when more infectious variants, which are, however, associated with milder courses, were present. These results provide insights into vaccine-related serologic responses, and the study should be expanded using additional vaccine doses and novel variants in the future. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

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15 pages, 1150 KiB

Open AccessEditor’s ChoiceReview

The Impact of COVID-19 on Pediatric Malignancy Diagnosis and Treatment: Never the Same but Lessons Learned

by Ghadir K. Katato, Prasiksha Sitaula, Avanti Gupte and Eman T. Al-Antary

Vaccines 2023, 11(3), 667; https://doi.org/10.3390/vaccines11030667 - 15 Mar 2023

Cited by 8 | Viewed by 3201

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected the pediatric oncology population globally. Over the course of 2 years, increasing reports have been made to better understand this entity and its pathologic complications on these patients. The pandemic has allowed healthcare [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected the pediatric oncology population globally. Over the course of 2 years, increasing reports have been made to better understand this entity and its pathologic complications on these patients. The pandemic has allowed healthcare providers, hospital systems, and leading oncologic societies to quickly adapt and formulate new guidelines for the effective understanding, management, and treatment of patients with pediatric malignancy. Full article

(This article belongs to the Special Issue Oncology in the Era of SARS-CoV-2)

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15 pages, 9874 KiB

Open AccessEditor’s ChoiceArticle

Phosphatidylserine-Exposing Annexin A1-Positive Extracellular Vesicles: Potential Cancer Biomarkers

by Gloria I. Perez, Matthew P. Bernard, Daniel Vocelle, Ahmed A. Zarea, Najla A. Saleh, Matthew A. Gagea, Doug Schneider, Maxine Bauzon, Terry Hermiston and Masamitsu Kanada

Vaccines 2023, 11(3), 639; https://doi.org/10.3390/vaccines11030639 - 13 Mar 2023

Cited by 16 | Viewed by 3681

Abstract

Under physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an “eat-me” signal for macrophages to prevent releasing self-immunogenic cellular components from dying cells [...] Read more.

Under physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an “eat-me” signal for macrophages to prevent releasing self-immunogenic cellular components from dying cells which could potentially lead to autoimmunity. However, increasing evidence indicates that viable cells can also expose PS on their surface. Interestingly, tumor cell-derived extracellular vesicles (EVs) externalize PS. Recent studies have proposed PS-exposing EVs as a potential biomarker for the early detection of cancer and other diseases. However, there are confounding results regarding subtypes of PS-positive EVs, and knowledge of PS exposure on the EV surface requires further elucidation. In this study, we enriched small EVs (sEVs) and medium/large EVs (m/lEVs) from conditioned media of breast cancer cells (MDA-MB-231, MDA-MB-468) and non-cancerous cells (keratinocytes, fibroblasts). Since several PS-binding molecules are available to date, we compared recombinant proteins of annexin A5 and the carboxylated glutamic acid domain of Protein S (GlaS), also specific for PS, to detect PS-exposing EVs. Firstly, PS externalization in each EV fraction was analyzed using a bead-based EV assay, which combines EV capture using microbeads and analysis of PS-exposing EVs by flow cytometry. The bulk EV assay showed higher PS externalization in m/lEVs derived from MDA-MB-468 cells but not from MDA-MB-231 cells, while higher binding of GlaS was also observed in m/lEVs from fibroblasts. Second, using single EV flow cytometry, PS externalization was also analyzed on individual sEVs and m/lEVs. Significantly higher PS externalization was detected in m/lEVs (annexin A1⁺) derived from cancer cells compared to m/lEVs (annexin A1⁺) from non-cancerous cells. These results emphasize the significance of PS-exposing m/lEVs (annexin A1⁺) as an undervalued EV subtype for early cancer detection and provide a better understanding of PS externalization in disease-associated EV subtypes. Full article

(This article belongs to the Special Issue Extracellular Vesicles: A New Mechanism of Intercellular Communication for Immune Regulation in Cancer, Autoimmune Diseases, and Infectious Diseases)

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13 pages, 1257 KiB

Open AccessEditor’s ChoiceArticle

Survivin (BIRC5) Peptide Vaccine in the 4T1 Murine Mammary Tumor Model: A Potential Neoadjuvant T Cell Immunotherapy for Triple Negative Breast Cancer: A Preliminary Study

by Scott R. Burkholz, Charles V. Herst, Richard T. Carback, Paul E. Harris and Reid M. Rubsamen

Vaccines 2023, 11(3), 644; https://doi.org/10.3390/vaccines11030644 - 13 Mar 2023

Cited by 14 | Viewed by 5074

Abstract

A triple negative breast cancer model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine [...] Read more.

A triple negative breast cancer model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine a tumor cell dose that resulted in sufficient tumor takes but allowed multiple serial measurements of tumor volumes, yet with minimal morbidity/mortality within the study period. Later, in a second cohort of mice, the survivin peptide microparticle vaccine was administered via intraperitoneal injection at the study start with a second dose given 14 days later. An orthotopic injection of 4T1 cells into the mammary tissue was performed on the same day as the administration of the second vaccine dose. The mice were followed for up to 41 days with subcutaneous measurements of tumor volume made every 3–4 days. Vaccination with survivin peptides was associated with a peptide antigen-specific gamma interferon enzyme-linked immunosorbent spot response in the murine splenocyte population but was absent from the control microparticle group. At the end of the study, we found that vaccination with adjuvanted survivin peptide microparticles resulted in statistically significant slower primary tumor growth rates in BALB/c mice challenged with 4T1 cells relative to the control peptideless vaccination group. These studies suggest that T cell immunotherapy specifically targeting survivin might be an applicable neoadjuvant immunotherapy therapy for triple negative breast cancer. More preclinical studies and clinical trials are needed to explore this concept further. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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11 pages, 522 KiB

Open AccessEditor’s ChoiceCommunication

Evolution and Progress of mRNA Vaccines in the Treatment of Melanoma: Future Prospects

by Dimitrios Bafaloukos, Ioanna Gazouli, Christos Koutserimpas and George Samonis

Vaccines 2023, 11(3), 636; https://doi.org/10.3390/vaccines11030636 - 13 Mar 2023

Cited by 30 | Viewed by 6988

Abstract

mRNA vaccines encoding tumor antigens may be able to sensitize the immune system of the host against cancer cells, enhancing antigen presentation and immune response. Since the breakout of the COVID19 pandemic, interest in mRNA vaccines has been accelerating, as vaccination against the [...] Read more.

mRNA vaccines encoding tumor antigens may be able to sensitize the immune system of the host against cancer cells, enhancing antigen presentation and immune response. Since the breakout of the COVID19 pandemic, interest in mRNA vaccines has been accelerating, as vaccination against the virus served as a measure to limit disease spread. Given that immunotherapy has been the cornerstone of melanoma treatment over the last several decades, further innate immunity enhancement by targeted mRNA vaccines could be the next pivotal achievement in melanoma treatment. Preclinical data coming from murine cancer models have already provided evidence of mRNA vaccines’ ability to induce host immune responses against cancer. Moreover, specific immune responses have been observed in melanoma patients receiving mRNA vaccines, while the recent KEYNOTE-942 trial may establish the incorporation of the mRNA-4157/V940 vaccine into the melanoma treatment algorithm, in combination with immune checkpoint inhibition. As the existing data are further tested and reviewed, investigators are already gaining enthusiasm about this novel, promising pathway in cancer therapy. Full article

(This article belongs to the Special Issue Oncology in the Era of SARS-CoV-2)

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13 pages, 1306 KiB

Open AccessEditor’s ChoiceArticle

Not All Conservatives Are Vaccine Hesitant: Examining the Influence of Misinformation Exposure, Political Ideology, and Flu Vaccine Acceptance on COVID-19 Vaccine Hesitancy

by Muhammad Ehab Rasul and Saifuddin Ahmed

Vaccines 2023, 11(3), 586; https://doi.org/10.3390/vaccines11030586 - 3 Mar 2023

Cited by 11 | Viewed by 4985

Abstract

Despite the mass availability of COVID-19 vaccines in the United States, many Americans are still reluctant to take a vaccine as an outcome from exposure to misinformation. Additionally, while scholars have paid attention to COVID-19 vaccine hesitancy, the influence of general vaccine hesitancy [...] Read more.

Despite the mass availability of COVID-19 vaccines in the United States, many Americans are still reluctant to take a vaccine as an outcome from exposure to misinformation. Additionally, while scholars have paid attention to COVID-19 vaccine hesitancy, the influence of general vaccine hesitancy for important viruses such as the flu has largely been ignored. Using nationally representative data from Pew Research Center’s American Trends Panel survey (Wave 79), this study examined the relationship between perceived misinformation exposure, COVID-19 vaccine hesitancy, flu vaccine acceptance, political ideology, and demographic trends. The findings suggest that those who accepted the flu vaccine were less likely to be COVID-19 vaccine-hesitant. In addition, moderation analyses showed that perceived misinformation exposure increases COVID-19 vaccine hesitancy for conservatives and moderates but not for liberals. However, perceived misinformation exposure influences COVID-19 vaccine hesitancy among conservatives only if they are also flu vaccine-hesitant. Perceived misinformation exposure has no role in COVID-19 vaccine hesitancy if individuals (irrespective of political ideology) are regular with their flu vaccine. The results suggest that the effect of misinformation exposure on negative attitudes toward COVID-19 may be associated with generalized vaccine hesitancy (e.g., flu). The practical and theoretical implications are discussed. Full article

(This article belongs to the Special Issue Recent Advances in Factors Associated with Vaccine Hesitancy and Acceptance)

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16 pages, 720 KiB

Open AccessEditor’s ChoiceArticle

Qualitative Insights into Vaccine Uptake of Nursing Staff in Long-Term Care Facilities in Finland

by Anna-Leena Lohiniva, Idil Hussein, Jaana-Marija Lehtinen, Jonas Sivelä, Suvi Hyökki, Hanna Nohynek, Pekka Nuorti and Outi Lyytikäinen

Vaccines 2023, 11(3), 530; https://doi.org/10.3390/vaccines11030530 - 23 Feb 2023

Cited by 6 | Viewed by 3950

Abstract

Vaccine hesitancy and refusal have undermined COVID-19 vaccination efforts of nursing staff. This study aimed to identify behavioral factors associated with COVID-19 vaccine uptake among unvaccinated nursing staff in long-term care facilities (LTCF) in Finland. Methodology: The study was based on the Theoretical [...] Read more.

Vaccine hesitancy and refusal have undermined COVID-19 vaccination efforts of nursing staff. This study aimed to identify behavioral factors associated with COVID-19 vaccine uptake among unvaccinated nursing staff in long-term care facilities (LTCF) in Finland. Methodology: The study was based on the Theoretical Domains Framework. Data were collected through qualitative in-depth interviews among nursing staff and managers of LTCFs. The analysis was based on thematic analysis. We identified seven behavioral domains, with several themes, that reduced the staff’s intention to get vaccinated: knowledge (information overload, inability to identify trustworthy information sources, lack of vaccine-specific and understandable scientific information), beliefs about consequences (incorrect perceptions about the vaccine effectiveness, and lack of trust in the safety of the vaccine), social influences (influence of family and friends), reinforcement (limited abilities of the management to encourage vaccination), beliefs about capabilities (pregnancy or desire to get pregnant), psychological factors (coping with changing opinion), and emotions (confusion, suspicion, disappointment, and fatigue). We also identified three behavioral domains that encouraged vaccine uptake: social influences (trust in health authorities), environmental context and resources (vaccination logistics), and work and professional role (professional pride). The study findings can help authorities to develop tailored vaccine promotion strategies for healthcare workers in LTCFs. Full article

(This article belongs to the Special Issue Vaccination Hesitancy across the Globe)

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13 pages, 434 KiB

Open AccessEditor’s ChoiceArticle

Development of Autoantibodies Following BNT162b2 mRNA COVID-19 Vaccination and Their Association with Disease Flares in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases (AIIRD) and the General Population: Results of 1-Year Prospective Follow-Up Study

by Tal Gazitt, Tali Eviatar, Jacqueline Shear, Roni Meidan, Victoria Furer, Joy Feld, Amir Haddad, Muna Elias, Nizar Hijazi, Nili Stein, Pninit Shaked Mishan, Anna Zetser, Hagit Peleg, Ori Elkayam and Devy Zisman

Vaccines 2023, 11(2), 476; https://doi.org/10.3390/vaccines11020476 - 17 Feb 2023

Cited by 13 | Viewed by 4136

Abstract

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence [...] Read more.

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed. Full article

(This article belongs to the Special Issue Antibody Response of Vaccines to SARS-CoV-2)

21 pages, 5788 KiB

Open AccessEditor’s ChoiceArticle

Toxicological Assessments of a Pandemic COVID-19 Vaccine—Demonstrating the Suitability of a Platform Approach for mRNA Vaccines

by Cynthia M. Rohde, Claudia Lindemann, Michael Giovanelli, Rani S. Sellers, Jan Diekmann, Shambhunath Choudhary, Lila Ramaiah, Annette B. Vogel, Yana Chervona, Alexander Muik and Ugur Sahin

Vaccines 2023, 11(2), 417; https://doi.org/10.3390/vaccines11020417 - 11 Feb 2023

Cited by 25 | Viewed by 7500

Abstract

The emergence of SARS-CoV-2 at the end of 2019 required the swift development of a vaccine to address the pandemic. Nonclinical GLP-compliant studies in Wistar Han rats were initiated to assess the local tolerance, systemic toxicity, and immune response to four mRNA vaccine [...] Read more.

The emergence of SARS-CoV-2 at the end of 2019 required the swift development of a vaccine to address the pandemic. Nonclinical GLP-compliant studies in Wistar Han rats were initiated to assess the local tolerance, systemic toxicity, and immune response to four mRNA vaccine candidates encoding immunogens derived from the spike (S) glycoprotein of SARS-CoV-2, encapsulated in lipid nanoparticles (LNPs). Vaccine candidates were administered intramuscularly once weekly for three doses at 30 and/or 100 µg followed by a 3-week recovery period. Clinical pathology findings included higher white blood cell counts and acute phase reactant concentrations, lower platelet and reticulocyte counts, and lower RBC parameters. Microscopically, there was increased cellularity (lymphocytes) in the lymph nodes and spleen, increased hematopoiesis in the bone marrow and spleen, acute inflammation and edema at the injection site, and minimal hepatocellular vacuolation. These findings were generally attributed to the anticipated immune and inflammatory responses to the vaccines, except for hepatocyte vacuolation, which was interpreted to reflect hepatocyte LNP lipid uptake, was similar between candidates and resolved or partially recovered at the end of the recovery phase. These studies demonstrated safety and tolerability in rats, supporting SARS-CoV-2 mRNA-LNP vaccine clinical development. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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8 pages, 249 KiB

Open AccessEditor’s ChoiceArticle

Association between COVID-19 and Seasonal Influenza Vaccines to Vaccine Hesitancy, Intolerance of Uncertainty and Mental Health

by Maayan Shacham, Yaira Hamama-Raz, Menachem Ben-Ezra and Yafit Levin

Vaccines 2023, 11(2), 403; https://doi.org/10.3390/vaccines11020403 - 9 Feb 2023

Cited by 7 | Viewed by 3226

Abstract

Vaccine hesitancy is a universal problem that is becoming more prevalent, ranging from partial acceptance to the complete refusal of various vaccines. The current study seeks to assess the relationship between vaccine hesitancy, intolerance of uncertainty, and mental health factors and those who [...] Read more.

Vaccine hesitancy is a universal problem that is becoming more prevalent, ranging from partial acceptance to the complete refusal of various vaccines. The current study seeks to assess the relationship between vaccine hesitancy, intolerance of uncertainty, and mental health factors and those who were vaccinated against COVID-19 and seasonal influenza in comparison to those who did not vaccinate against both or decided to be vaccinated with only one of these vaccines. Employing a cross-sectional design, 1068 Israeli participants were recruited via social media (mainly Facebook) and Whatsapp and completed questionnaires assessing vaccine hesitancy, intolerance of uncertainty, and mental health factors. Our results revealed that previous history of neither COVID-19 nor seasonal influenza vaccination was associated with increased vaccine hesitancy. In addition, individuals who received either one vaccine or both claimed elevated levels of intolerance of uncertainty and reported elevated levels of mental health symptoms. Therefore, an association between vaccine hesitancy and intolerance of uncertainty and mental health symptoms is demonstrated. Future campaigns against vaccine hesitancy may focus on the intolerance of uncertainty in vaccine-hesitant individuals. Full article

(This article belongs to the Special Issue Vaccines Hesitancy and Public Health)

12 pages, 286 KiB

Open AccessEditor’s ChoiceArticle

Predictors of Seasonal Influenza Vaccination Willingness among High-Risk Populations Three Years after the Onset of the COVID-19 Pandemic

by Aglaia Katsiroumpa, Panayota Sourtzi, Daphne Kaitelidou, Olga Siskou, Olympia Konstantakopoulou and Petros Galanis

Vaccines 2023, 11(2), 331; https://doi.org/10.3390/vaccines11020331 - 1 Feb 2023

Cited by 14 | Viewed by 3829

Abstract

High-risk populations are at increased risk of severe influenza-related illness, hospitalization, and death due to influenza. The aim of our study was to assess the willingness of high-risk populations to take the influenza vaccine for the 2022–2023 season, and to investigate the factors [...] Read more.

High-risk populations are at increased risk of severe influenza-related illness, hospitalization, and death due to influenza. The aim of our study was to assess the willingness of high-risk populations to take the influenza vaccine for the 2022–2023 season, and to investigate the factors associated with such willingness. We conducted a cross-sectional study in Greece in September 2022 using a convenience sample. We considered demographic characteristics, COVID-19-related variables, resilience, social support, anxiety, depression, and COVID-19-related burnout as potential predictors. Among participants, 39.4% were willing to accept the seasonal influenza vaccine, 33.9% were unwilling, and 26.8% were hesitant. Multivariable analysis identified that increased age and increased family support were associated with increased influenza vaccination willingness. Moreover, participants that have received COVID-19 booster doses were more willing to accept the influenza vaccine. In contrast, adverse effects because of COVID-19 vaccination and exhaustion due to measures against COVID-19 reduced influenza vaccination willingness. We found that the intention of high-risk populations to receive the influenza vaccine was low. Our study contributes to an increased understanding of the factors that affect vaccination willingness. Public health authorities could use this information to update vaccination programs against influenza. Emphasis should be given on safety and effectiveness issues. Full article

(This article belongs to the Special Issue Vaccines Hesitancy and Public Health)

18 pages, 2921 KiB

Open AccessEditor’s ChoiceArticle

Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models

by Nicole Roth, Janina Gergen, Kristina Kovacikova, Stefan O. Mueller, Lorenz Ulrich, Jacob Schön, Nico Joel Halwe, Charlie Fricke, Björn Corleis, Anca Dorhoi, Donata Hoffmann, Martin Beer, Domenico Maione, Benjamin Petsch and Susanne Rauch

Vaccines 2023, 11(2), 318; https://doi.org/10.3390/vaccines11020318 - 31 Jan 2023

Cited by 8 | Viewed by 4451

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represented the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike [...] Read more.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represented the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike (S) protein, these Omicron subvariants have collectively resulted in increased viral transmission and disease incidence. This necessitates the development and characterization of vaccines incorporating later emerging S proteins to enhance protection against VOC. In this context, bivalent vaccine formulations may induce broad protection against VOC and potential future SARS-CoV-2 variants. Here, we report preclinical data for a lipid nanoparticle (LNP)-formulated RNActive^® N1-methylpseudouridine (N1mΨ) modified mRNA vaccine (CV0501) based on our second-generation SARS-CoV-2 vaccine CV2CoV, encoding the S protein of Omicron BA.1. The immunogenicity of CV0501, alone or in combination with a corresponding vaccine encoding the ancestral S protein (ancestral N1mΨ), was first measured in dose-response and booster immunization studies performed in Wistar rats. Both monovalent CV0501 and bivalent CV0501/ancestral N1mΨ immunization induced robust neutralizing antibody titers against the BA.1, BA.2 and BA.5 Omicron subvariants, in addition to other SARS-CoV-2 variants in a booster immunization study. The protective efficacy of monovalent CV0501 against live SARS-CoV-2 BA.2 infection was then assessed in hamsters. Monovalent CV0501 significantly reduced SARS-CoV-2 BA.2 viral loads in the airways, demonstrating protection induced by CV0501 vaccination. CV0501 has now advanced into human Phase 1 clinical trials (ClinicalTrials.gov Identifier: NCT05477186). Full article

(This article belongs to the Section COVID-19 Vaccines and Vaccination)

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14 pages, 1512 KiB

Open AccessEditor’s ChoiceArticle

The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses

by Lorena Usero, Lorna Leal, Carmen Elena Gómez, Laia Miralles, Elena Aurrecoechea, Ignasi Esteban, Berta Torres, Alexy Inciarte, Beatriz Perdiguero, Mariano Esteban, Felipe García and Montserrat Plana

Vaccines 2023, 11(2), 286; https://doi.org/10.3390/vaccines11020286 - 28 Jan 2023

Cited by 7 | Viewed by 3701

Abstract

The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3′-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, [...] Read more.

The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3′-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, including different CD4 and CD8 T-cell epitopes functionally associated with HIV control in transfected monocyte-derived dendritic cells (MDDCs) obtained from HIV infected patients. In vitro assays were used to test the mRNAs alone and in combination with immunomodulator agents, such as the TLR-7 agonist Vesatolimod and the PD-1 antagonist Nivolumab to try to improve HIV-specific cellular immune responses. Combining the mRNAs with the immunomodulators enhanced HIV-specific T-cell responses, together with the secretion of IFNγ, IP10, MIP-1α, and MIP-1β, which are fundamental mediators of viral control. Our data suggest that the mRNA vaccine prototypes TMEP-B and TMEP-Bmod, when combined with Vesatolimod and/or Nivolumab, could achieve functional cure for patients with HIV. Full article

(This article belongs to the Special Issue HIV Infection and Vaccination)

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