Vaccines

18 pages, 649 KiB

Open AccessArticle

Immunogenic Properties of a Novel Hepatitis A Vaccine Candidate Based on a Fast-Growing Viral Strain

by Maria Isabel Costafreda, Malén Massot-Cladera, Gemma Chavarria-Miró, Alba Arrebola, Àngels Franch-Masferrer, Maria J. Rodríguez-Lagunas, Adán Martínez-Velázquez, Albert Blanco, Albert Bosch, Susana Guix, Margarida Castell and Rosa Maria Pintó

Vaccines 2025, 13(5), 446; https://doi.org/10.3390/vaccines13050446 - 23 Apr 2025

Abstract

Background/Objectives: Hepatitis A virus (HAV) yearly causes over 150 million new infections and around 40,000 deaths. Current vaccines are based on strains that grow poorly in cell culture, leading to high production costs and limited availability. This study aimed to compare the immunogenic [...] Read more.

Background/Objectives: Hepatitis A virus (HAV) yearly causes over 150 million new infections and around 40,000 deaths. Current vaccines are based on strains that grow poorly in cell culture, leading to high production costs and limited availability. This study aimed to compare the immunogenic properties of a novel HAV vaccine candidate based on the fast-growing HM175-HP strain with those of the parental slow-growing HM175-L0 strain, which derives from the cytopathic HM175 strain, like the prototype strain used in certain existing vaccines. Methods: The humoral and cellular immune response elicited by either HM175-HP or HM175-L0 vaccines was assessed in female BALB/c mice. Results: Both HM175-HP and HM175-L0 vaccines induced comparable levels of anti-HAV IgG, as well as similar numbers of antibody-secreting cells and cellular proliferation rates in immunized mice. Importantly, anti-HAV antibodies developed by HM175-HP-immunized mice were able to neutralize the HM175-L0 strain. In addition, both vaccines induced anti-HAV IgG1 antibodies, which are associated with Th2 immune response, but the HM175-HP vaccine showed a tendency to produce a greater IgG2a response, suggesting that it might elicit a higher Th1 response, which is of utmost importance for host defense against viruses. Conclusions: Our findings indicated that the fast-growing HM175-HP strain has similar immunogenic properties to the vaccine prototype-like HM175-L0, making it a promising candidate to reduce the elevated costs and time-consuming procedures of producing the current HAV vaccines. The novel HM175-HP-based vaccine would therefore facilitate mass vaccination programs and prevent vaccine shortages. Full article

(This article belongs to the Special Issue Hepatitis Vaccines: Safety, Efficacy and Global Impact)

20 pages, 1406 KiB

Open AccessReview

The Role of Internet Information on Anti-HPV Vaccines: A Comprehensive Overview of a Double-Edged Sword

by Luca Giannella, Camilla Grelloni, Leonardo Natalini, Gianmarco Sartini, Federica Lavezzo, Camilla Cicoli, Marco Bernardi, Mila Bordini, Martina Petrini, Jessica Petrucci, Tomas Terenzi, Giovanni Delli Carpini, Jacopo Di Giuseppe and Andrea Ciavattini

Vaccines 2025, 13(5), 445; https://doi.org/10.3390/vaccines13050445 - 23 Apr 2025

Abstract

Cervical cancer (CC) is the only cancer that has the possibility of primary and secondary prevention. Despite this, it is one of the leading causes of cancer death among women, especially in developing countries. The World Health Organization has set the ambitious goal [...] Read more.

Cervical cancer (CC) is the only cancer that has the possibility of primary and secondary prevention. Despite this, it is one of the leading causes of cancer death among women, especially in developing countries. The World Health Organization has set the ambitious goal of eliminating CC by 2030 by suggesting specific types of intervention. Unfortunately, to date, we are very far from this goal at a global level, including developed countries. Implementing vaccination coverage among the target population is one of the strategies to be pursued in this area. Achieving this goal should include combating misinformation about the HPV vaccine, which is one of the main reasons for vaccination hesitancy. Such conspiracy theories are prevalent on social media, one of the primary sources of information for adults and adolescents today. In this regard, the Internet plays a significant role in disseminating information about the HPV vaccine, both positively and negatively. The Internet provides easy access to information about the HPV vaccine, including its safety, efficacy, recommended dosing schedule, and potential side effects. It may promote vaccine advocacy and debunking vaccine myths. On the other hand, the Internet may be the place for disseminating misinformation and influencing vaccine decision making. It is a double-edged sword in shaping public discourse and perceptions about the HPV vaccine. This overview aims to assess the literature on this topic in depth to promote evidence-based information, analyze the social channels through which misinformation spreads, and leverage digital health interventions essential for promoting HPV vaccination and reducing the burden of HPV-related diseases. Full article

(This article belongs to the Special Issue Human Papillomavirus Vaccine Against Cervical Cancer: New Usage Strategies and Coverage Issues)

51 pages, 1390 KiB

Open AccessReview

Navigating the Purification Process: Maintaining the Integrity of Replication-Competent Enveloped Viruses

by Adrian Schimek, Judy King Man Ng and Jürgen Hubbuch

Vaccines 2025, 13(5), 444; https://doi.org/10.3390/vaccines13050444 - 23 Apr 2025

Abstract

Replication-competent virus particles hold significant therapeutic potential in application as oncolytic viruses or cancer vaccines. Ensuring the viral integrity of these particles is crucial for their infectivity, safety, and efficacy. Enveloped virus particles, in particular, offer large gene insert capacities and customizable target [...] Read more.

Replication-competent virus particles hold significant therapeutic potential in application as oncolytic viruses or cancer vaccines. Ensuring the viral integrity of these particles is crucial for their infectivity, safety, and efficacy. Enveloped virus particles, in particular, offer large gene insert capacities and customizable target specificity. However, their sensitivity to environmental factors presents challenges in bioprocessing, potentially compromising high quality standards and cost-effective production. This review provides an in-depth analysis of the purification process steps for replication-competent enveloped virus particles, emphasizing the importance of maintaining viral integrity. It evaluates bioprocessing methods from cell culture harvest to final sterile filtration, including centrifugation, chromatographic, and filtration purification techniques. Furthermore, the manuscript delves into formulation and storage strategies necessary to preserve the functional and structural integrity of virus particles, ensuring their long-term stability and therapeutic efficacy. To assess the impact of process steps on particles and determine their quality and integrity, advanced analytical methods are required. This review evaluates commonly used methods for assessing viral integrity, such as infectious titer assays, total virus particle quantification, and structural analysis. By providing a comprehensive overview of the current state of bioprocessing for replication-competent enveloped virus particles, this review aims to guide researchers and industry professionals in developing robust and efficient purification processes. The insights gained from this analysis will contribute to the advancement of virus-based therapeutics, ultimately supporting the development of safe, effective, and economically viable treatments for various diseases. Full article

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

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10 pages, 765 KiB

Open AccessArticle

Universal Health Coverage and Preparedness Payoffs: Global COVID-19 Vaccination Rates

by Alon Rasooly, Zachary Lebowitz, Pavel Ursu and Dorit Nitzan

Vaccines 2025, 13(5), 443; https://doi.org/10.3390/vaccines13050443 - 23 Apr 2025

Abstract

Objective: The pandemic exposed global inequities in terms of health system capacities and vaccination coverage. This study evaluated the relationship between countries’ preparedness and COVID-19 vaccination rates. Methods: In this ecological study, we gathered global pre-pandemic data on country-level States Parties [...] Read more.

Objective: The pandemic exposed global inequities in terms of health system capacities and vaccination coverage. This study evaluated the relationship between countries’ preparedness and COVID-19 vaccination rates. Methods: In this ecological study, we gathered global pre-pandemic data on country-level States Parties Self-Assessment Annual Reporting (SPAR) and universal health coverage (UHC) indexes. We then analyzed their relationship with COVID-19 vaccination rates in 2021–2022, using bivariate and multivariate analyses, including confounders, such as the country’s income classification and population demographics. Findings: The mean vaccination rates increased from 32.2% in October 2021 to 51.2% by August 2022. The UHC and SPAR indexes showed strong positive correlations with vaccination rates (r = 0.76 and r = 0.66, respectively, p < 0.001). In regard to the multivariate analyses, both the UHC (B = 0.81, 95% CI: 0.56–1.06) and SPAR (B = 0.34, 95% CI: 0.19–0.49) indexes remained significant predictors of vaccination rates, even after adjusting for country income level, with their influence strengthening over time, while income level effects diminished. Conclusions: This study underscores the critical importance of preparedness efforts, as gauged by the SPAR and UHC indexes, in shaping the effectiveness of COVID-19 vaccination responses globally. Strengthening preparedness measures is important for optimizing vaccination strategies and achieving broader immunization coverage targets. Full article

(This article belongs to the Special Issue Vaccines and Vaccinations in the Pandemic Period)

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21 pages, 4951 KiB

Open AccessArticle

Evaluation of Immunogenicity of Mycobacterium tuberculosis ag85ab DNA Vaccine Delivered by Pulmonary Administration

by Haimei Zhao, Zhen Zhang, Yong Xue, Nan Wang, Yinping Liu, Xihui Ma, Lan Wang, Xiaoou Wang, Danyang Zhang, Junxian Zhang, Xueqiong Wu and Yan Liang

Vaccines 2025, 13(5), 442; https://doi.org/10.3390/vaccines13050442 - 23 Apr 2025

Abstract

Background: Tuberculosis (TB) is a respiratory infectious disease, and the current TB vaccine has low local lung protection. We aim to optimize immune pathways to improve the immunogenicity of vaccines. Methods: In the immunogenicity study, 50 BALB/c mice were randomly divided into the [...] Read more.

Background: Tuberculosis (TB) is a respiratory infectious disease, and the current TB vaccine has low local lung protection. We aim to optimize immune pathways to improve the immunogenicity of vaccines. Methods: In the immunogenicity study, 50 BALB/c mice were randomly divided into the following: (1) phosphate buffered saline (PBS)+intramuscular injection combined with electroporation (EP) group (100 μL), (2) pVAX1+EP group (50 μg/100 μL), (3) ag85ab+EP group (50 μg/100 μL), (4) pVAX1+pulmonary delivery (PD) group (50 μg/50 μL), and (5) ag85ab+PD group (50 μg/50 μL). Immunization was given once every 2 weeks for a total of three times. The number of IFN-γ-secreting lung and spleen lymphocytes was determined by enzyme-linked immunospot assay (ELISPOT). The levels of Th1, Th2, and Th17 cytokines in the culture supernatants of lung and spleen lymphocytes were detected with the Luminex method. The proportion of FoxP3 regulatory T cells in splenocytes was determined by flow cytometry. The levels of IgG-, IgG1-, and IgG2a-specific antibodies in plasma and IgA antibody in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay (ELISA). Results: The PD and EP routes of Mycobacterium tuberculosis (M. tb) ag85ab DNA vaccine can effectively induce the responses of IFN-γ-secreting lung and spleen lymphocytes, and induce dominant Th1 and Th17 cell immune responses. The PD route can induce earlier, greater numbers and stronger responses of pulmonary effector T cells, with higher levels of the specific antibody IgA detected in BALF. High levels of the specific antibodies IgG, IgG1, and IgG2α were detected in the plasma of mice immunized by the EP route. Conclusions: The PD route of DNA vaccines can more effectively stimulate the body to produce strong cellular and mucosal immunity than the EP route, especially local cellular immunity in the lungs, which can provide early protection for the lungs. It can significantly improve the immunogenicity of the ag85ab DNA vaccine, suggesting a feasible and effective approach to DNA immunization. Full article

(This article belongs to the Special Issue Immunobiology of Mycobacterium tuberculosis and Its Implication in Vaccine Design)

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16 pages, 2737 KiB

Open AccessArticle

Immune Protection Gap Between Porcine Reproductive and Respiratory Syndrome Subunit Vaccine (N Protein) and Live Vaccine

by Mengpo Zhao, Pian Zhang, Xiaoxiao Zhang, Shengjun Luo, Ziguo Yuan, Yanju Huang, Gang Wang, Hua Xiang, Yuan Huang, Yuzhu Jin, Jing Chen and Xiaohu Wang

Vaccines 2025, 13(5), 441; https://doi.org/10.3390/vaccines13050441 - 23 Apr 2025

Abstract

Objectives: To evaluate the immunoprotective effect of a PRRSV N protein subunit vaccine on piglets using a live PRRSV vaccine as a control. Methods: The HEK-293T eukaryotic expression system was used to produce PRRSV N protein, and then PRRSV N protein [...] Read more.

Objectives: To evaluate the immunoprotective effect of a PRRSV N protein subunit vaccine on piglets using a live PRRSV vaccine as a control. Methods: The HEK-293T eukaryotic expression system was used to produce PRRSV N protein, and then PRRSV N protein was immunized with a commercial live PRRS vaccine. The immunoprotective effect of the PRRSV N protein subunit vaccine on piglets was evaluated by detecting the antibody level in the immunized piglets, and the clinical symptoms, pathological changes, and survival rate of the immunized piglets. Results: At 21 and 28 days after immunization, the serum N protein-specific antibody levels of piglets in the live PRRSV vaccine group were higher than those in the N protein group. After PRRSV infection, piglets in the N protein group and the DMEM group showed more severe clinical symptoms such as respiratory distress, loss of appetite, skin redness, and diarrhea than those in the live vaccine group. The rectal temperature of piglets in the live vaccine group remained below 40 °C, and only one piglet died on day 11 post-infection; in the PRRSV N protein group, the rectal temperature of some piglets exceeded 41 °C, and four piglets died on days 9, 11, 14, and 20 post-infection. In addition, pathologic damage to organs such as lungs, liver, lymph nodes, spleen, and kidneys was more severe in the N protein group than in the live vaccine group. Furthermore, histopathology and immunohistochemistry showed more pronounced organ damage (lungs, liver, lymph nodes, spleen, and kidneys) and higher viral loads in the N protein group compared to the live vaccine group. Conclusions: The PRRS subunit vaccine (N protein) expressed in the HEK-293T eukaryotic system did not protect piglets from heterologous PRRSV infection compared with the PRRS live vaccine. Full article

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

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12 pages, 990 KiB

Open AccessArticle

Phylogenetic Analysis of a Newcastle Disease Virus Strain Isolated from Domestic Poultry and Its Potential for Vaccine Development in the Republic of Kazakhstan

by Nurlan Akmyrzayev, Sholpan Ryskeldinova, Aigerim Mailybayeva, Yerken Kozhamkulov, Aigerim Sagymbayeva, Yeldos Myrzakhmetov, Yerbol Burashev, Nurlan Kozhabergenov, Bekbolat Usserbayev and Nurika Assanzhanova

Vaccines 2025, 13(5), 440; https://doi.org/10.3390/vaccines13050440 - 23 Apr 2025

Abstract

Background/Objectives: Despite the availability of Newcastle disease (ND) vaccines, outbreaks have continued to occur for more than six decades, with significant economic consequences for the global poultry industry. The variability of the Newcastle disease virus requires constant monitoring, detection of new cases, and [...] Read more.

Background/Objectives: Despite the availability of Newcastle disease (ND) vaccines, outbreaks have continued to occur for more than six decades, with significant economic consequences for the global poultry industry. The variability of the Newcastle disease virus requires constant monitoring, detection of new cases, and studies of the origin of the pathogen. The aim of this study was to develop an inactivated ND vaccine using a topical strain with different adjuvants and to compare them for stability, harmlessness, immunogenicity, and efficacy. Methods: A phylogenetic study of the F-gene of the ND strain isolated in Kazakhstan was conducted. The strain, which was selected to create a vaccine for the prevention of the disease, was revealed to belong to genotype VII class II and uploaded to GenBank (NCBI). Two different adjuvants, Montanide ISA 70 VG and Montanide ISA 78 VG, were used to create the vaccine. Birds were vaccinated intramuscularly. Results: Evaluations of antibody titers in the vaccinated groups during the experiment showed that the vaccines induced adequate levels of antibodies to provide protection against the virulent virus. High antibody titers were observed in the hemagglutination inhibition assay (HAI) in the vaccinated groups as early as 14 days post-vaccination in 100% of birds. The average antibody titer in both vaccinated groups exceeded 7 log2, sufficient to prevent clinical signs. None of the vaccinated birds exhibited clinical signs following control infection, whereas unvaccinated birds developed clinical manifestations within three days post-infection, leading to 100% mortality. Conclusions: The vaccine developed using the epizootic topical strain is stable, harmless, immunogenic, and effective when challenged with a virulent ND virus strain at a dose of 105 EID_50/mL. Full article

(This article belongs to the Section Veterinary Vaccines)

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16 pages, 238 KiB

Open AccessConference Report

WHO Workshop Report: Regulatory Science to Inform Clinical Pathways for Shigella Vaccines Intended for Use in Children in Low- and Middle-Income Countries

by Robert W. Kaminski, Patricia B. Pavlinac, James A. Platts-Mills, Elizabeth T. Rogawski McQuade, William P. Hausdorff, Richard A. Isbrucker, Kirsten S. Vannice, Marco Cavaleri, Sonali Kochhar, Kirsty Mehring-LeDoare, Godwin Enwere, Annelies Wilder-Smith, Karen L. Kotloff, Samba Sow and Birgitte K. Giersing

Vaccines 2025, 13(5), 439; https://doi.org/10.3390/vaccines13050439 - 23 Apr 2025

Abstract

Infectious diarrhea caused by Shigella remains a significant global health concern, and several vaccine candidates are approaching phase III clinical studies in the target population of young children in low- and middle-income countries. The World Health Organization (WHO) has published preferred product characteristics [...] Read more.

Infectious diarrhea caused by Shigella remains a significant global health concern, and several vaccine candidates are approaching phase III clinical studies in the target population of young children in low- and middle-income countries. The World Health Organization (WHO) has published preferred product characteristics (PPCs) for Shigella vaccines to provide strategic guidance that aids in advancing product development and highlights policy considerations for use in LMIC settings where the vaccine is most needed. However, the selection of appropriate clinical endpoints was not clearly defined within the PPCs and remains an important issue for phase III study design. Previously, an expert panel identified areas of alignment and consensus on many clinical study design components while also recognizing that further discussions and data were required to solidify recommendations on key study design aspects. Therefore, WHO convened a diverse range of stakeholders, including manufacturers, regulators, and policymakers across national, regional, and global levels, with the aim of achieving consensus and soliciting inputs from the regulatory community surrounding vaccine phase III study design considerations. The intent of this report is to outline the key points from those discussions to inform the phase III design strategies and investment decisions of product developers and donors and to share recommendations for next steps. Full article

(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)

15 pages, 1632 KiB

Open AccessArticle

Evaluation of the Potency of the First Commercial Vaccine for Clostridioides difficile Infection in Piglets and Comparison with the Humoral Response in Rabbits

by Victor Santos do Amarante, João Victor Ferreira Campos, Thayanne Gabryelle Viana de Souza, Yasmin Gonçalves de Castro, Kelly Mara Gomes Godoy and Rodrigo Otávio Silveira Silva

Vaccines 2025, 13(5), 438; https://doi.org/10.3390/vaccines13050438 - 22 Apr 2025

Abstract

Clostridioides difficile is an anaerobic bacterium that causes disease in both animals and humans. Despite the known significance of this agent, there are no commercial vaccines available for humans, and only one immunogen is marketed for swine. However, no studies have evaluated this [...] Read more.

Clostridioides difficile is an anaerobic bacterium that causes disease in both animals and humans. Despite the known significance of this agent, there are no commercial vaccines available for humans, and only one immunogen is marketed for swine. However, no studies have evaluated this vaccine. Background/Objectives: Therefore, the aim of this study was to assess the potency of the first commercial vaccine for C. difficile infection in piglets and to compare the humoral response in rabbits and sows. Methods: Pregnant sows were divided into two groups: a vaccinated group (n = 12), receiving two doses before farrowing, according to the manufacturer’s recommendation, and an unvaccinated control group (n = 6). Blood samples were taken from sows and also from piglets up to two days after birth. In addition, two groups of New Zealand rabbits (Oryctolagus cuniculus) received either a half-dose (G1) or a full-dose (G2) of the vaccine, with a control group receiving sterile saline (0.85%). Rabbits were vaccinated twice, 21 days apart, with blood samples collected before each dose and 14 days after the final dose. A serum neutralization assay in Vero cells was performed to evaluate the titers of neutralizing antibodies. Results: The vaccine demonstrated immunogenicity by stimulating the production of neutralizing antibodies in both rabbits and sows. Additionally, these antibodies were passively transferred to piglets through colostrum, reaching levels comparable to those found in sows. Furthermore, vaccinated rabbits developed antibody titers that do not significantly differ from those obtained in sows and piglets. Conclusions: The tested vaccine can induce a humoral immune response against C. difficile A/B toxins in sows and these antibodies are passively transferred to neonatal piglets through colostrum. Also, the vaccination of rabbits might be a useful alternative for evaluating the potency of vaccines against C. difficile. Full article

(This article belongs to the Special Issue Vaccine and Vaccination in Veterinary Medicine)

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15 pages, 5002 KiB

Open AccessArticle

Vaccination Schedules Recommended by the Centers for Disease Control and Prevention: From Human-Readable to Machine-Processable

by Xia Jing, Hua Min, Yang Gong, Mytchell A. Ernst, Aneesa Weaver, Chloe Crozier, David Robinson, Dean F. Sittig, Paul G. Biondich, Samuil Orlioglu, Akash Shanmugan Boobalan, Kojo Abanyie, Richard D. Boyce, Adam Wright, Christian Nøhr, Timothy D. Law, Arild Faxvaag, Lior Rennert and Ronald W. Gimbel

Vaccines 2025, 13(5), 437; https://doi.org/10.3390/vaccines13050437 - 22 Apr 2025

Abstract

Background: Reusable, machine-processable clinical decision support system (CDSS) rules have not been widely achieved in the medical informatics field. This study introduces the process, results, challenges faced, and lessons learned while converting the United States of America Centers for Disease Control and Prevention [...] Read more.

Background: Reusable, machine-processable clinical decision support system (CDSS) rules have not been widely achieved in the medical informatics field. This study introduces the process, results, challenges faced, and lessons learned while converting the United States of America Centers for Disease Control and Prevention (CDC)-recommended immunization schedules (2022) to machine-processable CDSS rules. Methods: We converted the vaccination schedules into tabular, charts, MS Excel, and clinical quality language (CQL) formats. The CQL format can be automatically converted to a machine-processable format using existing tools. Therefore, it was regarded as a machine-processable format. The results were reviewed, verified, and tested. Results: We have developed 465 rules for 19 vaccines in 13 categories, and we have shared the rules via GitHub to make them publicly available. We used cross-review and cross-checking to validate the CDSS rules in tabular and chart formats. The CQL files were tested for syntax and logic with hypothetical patient HL7 FHIR resources. Our rules can be reused and shared by the health IT industry, CDSS developers, medical informatics educators, or clinical care institutions. The unique contributions of our work are twofold: (1) we created ontology-based, machine-processable, and reusable immunization recommendation rules, and (2) we created and shared multiple formats of immunization recommendation rules publicly which can be a valuable resource for medical and medical informatics communities. Conclusions: These CDSS rules can be important contributions to informatics communities, reducing redundant efforts, which is particularly significant in resource-limited settings. Despite the maturity and concise presentation of the CDC recommendations, careful attention and multiple layers of verification and review are necessary to ensure accurate conversion. The publicly shared CDSS rules can also be used for health and biomedical informatics education and training purposes. Full article

(This article belongs to the Special Issue Health Technology Assessment of Vaccination: Strategies, Public Health and Values)

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34 pages, 9543 KiB

Open AccessSystematic Review

Helminth Coinfections Modulate Disease Dynamics and Vaccination Success in the Era of Emerging Infectious Diseases

by Brice Armel Nembot Fogang, Linda Batsa Debrah, Michael Owusu, George Agyei, Julia Meyer, Jonathan Mawutor Gmanyami, Manuel Ritter, Kathrin Arndts, Derrick Adu Mensah, Tomabu Adjobimey, Achim Hörauf and Alexander Yaw Debrah

Vaccines 2025, 13(5), 436; https://doi.org/10.3390/vaccines13050436 - 22 Apr 2025

Abstract

Background/Objectives: Helminth infections, particularly prevalent in low- and middle-income countries, have been extensively studied for their effects on human health. With the emergence of new infectious diseases like SARS-CoV-2 and Ebola, their impact on disease outcomes become more apparent. While individual studies [...] Read more.

Background/Objectives: Helminth infections, particularly prevalent in low- and middle-income countries, have been extensively studied for their effects on human health. With the emergence of new infectious diseases like SARS-CoV-2 and Ebola, their impact on disease outcomes become more apparent. While individual studies have explored the impact of helminth co-infections on disease severity and vaccine efficacy, the findings are often inconsistent and context-dependent. Furthermore, the long-term effects of helminth-mediated immunosuppression on vaccine efficacy and its broader implications for co-infections in endemic regions remain not fully understood. Methods: This systematic review conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines synthesizes the current evidence, identifies patterns, and highlights areas needing further research, offering a cohesive understanding of the topic. PubMed, Scopus, Google Scholar, and Cochrane Library were searched to include studies published from 2003 to February 2025. Results: Co-infection reveals a dual role of helminths in modulating immune responses, with both beneficial and detrimental interactions reported across studies. It may confer benefits against respiratory viral infections by muting hyper-inflammation associated with the severity of conditions like COVID-19, Influenza, and RSV. However, they can exacerbate disease outcomes in most bacteria and blood-borne viral conditions by impairing immune functions, such as neutrophil recruitment and antibody response, leading to more severe infections and higher viral loads. The stage of helminth infection also appears critical, with early-stage infections sometimes offering protection, while late-stage infections may worsen disease outcomes. Helminth infection can also negatively impact vaccine efficacy by suppressing B cell activity, reducing antibody levels, and decreasing vaccine effectiveness against infectious diseases. This immunosuppressive effect may persist after deworming, complicating efforts to restore vaccine efficacy. Maternal helminth infections also significantly influence neonatal immunity, affecting newborn vaccine responses. Conclusions: There is a need for targeted interventions and further research in helminth-endemic regions to mitigate the adverse effects on vaccine efficacy and improve public health outcomes. Full article

(This article belongs to the Special Issue Interplay between Host and Pathogen: Effects of Infection and Immune Responses)

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26 pages, 1278 KiB

Open AccessReview

Developing a Vaccine Against Human Cytomegalovirus: Identifying and Targeting HCMV’s Immunological Achilles’ Heel

by Anastasia Lankina, Marta Raposo, Alexander Hargreaves, Claire Atkinson, Paul Griffiths and Matthew B. Reeves

Vaccines 2025, 13(5), 435; https://doi.org/10.3390/vaccines13050435 - 22 Apr 2025

Abstract

Human cytomegalovirus (HCMV) is a critical pathogen in immunocompromised populations, such as organ transplant recipients as well as congenitally infected neonates with immature immune systems. Despite decades of research and the growing financial burden associated with the management of HCMV, there is no [...] Read more.

Human cytomegalovirus (HCMV) is a critical pathogen in immunocompromised populations, such as organ transplant recipients as well as congenitally infected neonates with immature immune systems. Despite decades of research and the growing financial burden associated with the management of HCMV, there is no licensed vaccine to date. In this review, we aim to outline the complexity of HCMV and the antigens it presents and the journey and challenges of developing an effective HCMV vaccine, as well as further highlight the recent analyses of the most successful vaccine candidate so far—gB/MF59. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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2 pages, 133 KiB

Open AccessCorrection

Correction: Dors et al. Effect of Vaccination Against E. coli, C. perfringens Type A/C on Piglet Productive and Clinical Parameters Under Field Conditions. Vaccines 2024, 12, 1185

by Arkadiusz Dors, Robert Panek, Wojciech Łużyński, Krzysztof Janeczko, Agata Augustyniak, Hanna Turlewicz-Podbielska, Ewelina Czyżewska-Dors and Małgorzata Pomorska-Mól

Vaccines 2025, 13(5), 434; https://doi.org/10.3390/vaccines13050434 - 22 Apr 2025

Abstract

The authors would like to make the following corrections to this published paper [...] Full article

27 pages, 819 KiB

Open AccessReview

HPV Vaccine Delivery Strategies to Reach Out-of-School Girls in Low- and Middle-Income Countries: A Narrative Review

by Erica N. Rosser, Megan D. Wysong, Joseph G. Rosen, Rupali J. Limaye and Soim Park

Vaccines 2025, 13(5), 433; https://doi.org/10.3390/vaccines13050433 - 22 Apr 2025

Abstract

Background/Objectives: Low- and middle-income countries (LMICs) have the highest global burden of cervical cancer deaths. Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination, and in LMICs, global recommendations to vaccinate girls aged 9–14 years against HPV are generally implemented [...] Read more.

Background/Objectives: Low- and middle-income countries (LMICs) have the highest global burden of cervical cancer deaths. Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination, and in LMICs, global recommendations to vaccinate girls aged 9–14 years against HPV are generally implemented through school-based immunization platforms. Unfortunately, this strategy risks missing out-of-school (OOS) girls (i.e., girls not enrolled in formal schools). This narrative review maps the literature and synthesizes existing evidence on service delivery strategies for reaching OOS girls with HPV vaccination in LMICs. Methods: Using relevant databases, we conducted a narrative review of published, peer-reviewed literature to map and synthesize the existing evidence on effective service delivery strategies for reaching OOS girls with HPV vaccination in LMICs. Results: The 21 articles identified presented findings on strategies to reach OOS girls, with the most frequently cited strategies being facility-based and community outreach approaches. Authors also described community-based strategies used to identify and enumerate OOS girls, including peer tracing, church outreach initiatives, as well as partnerships with local groups (e.g., civil service organizations) and individuals (e.g., healthcare workers, teachers). The articles discussed barriers at the individual (e.g., lack of parental consent), facility/program delivery (e.g., lack of transportation for vaccines), and community (e.g., distance from homes to vaccination services) levels to HPV vaccine delivery, as well as solutions at the facility/program delivery (e.g., pilot programs) and community (e.g., multi-level partnerships) levels. Conclusions: Additional research is needed to evaluate implementation strategies targeting OOS girls with HPV vaccination. A better understanding of these strategies can provide valuable insights for HPV vaccine policymakers, healthcare providers, and program implementers. Full article

(This article belongs to the Special Issue Prevention of Human Papillomavirus (HPV) and Vaccination)

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17 pages, 2604 KiB

Open AccessReview

Chronicling the Journey of Pneumococcal Conjugate Vaccine Introduction in India

by Pawan Kumar, Arindam Ray, Amrita Kumari, Abida Sultana, Rhythm Hora, Kapil Singh, Rashmi Mehra, Amanjot Kaur, Seema Singh Koshal, Syed F. Quadri, Shyam Kumar Singh and Arup Deb Roy

Vaccines 2025, 13(4), 432; https://doi.org/10.3390/vaccines13040432 - 21 Apr 2025

Abstract

Background: Globally, pneumonia claims the lives of about 700,000 children under the age of 5 every year. Pneumococcal conjugate vaccine (PCV) was introduced in India phase-wise, beginning in high-burden states, and the rollout was completed nationwide by 2021—representing a major initiative by the [...] Read more.

Background: Globally, pneumonia claims the lives of about 700,000 children under the age of 5 every year. Pneumococcal conjugate vaccine (PCV) was introduced in India phase-wise, beginning in high-burden states, and the rollout was completed nationwide by 2021—representing a major initiative by the Ministry of Health and Family Welfare (MoHFW). Despite the challenges posed by the COVID-19 pandemic, the campaign succeeded in maintaining progress and achieving nationwide coverage. This narrative review highlights the significant decisions, processes, and coordinated efforts of the various stakeholders involved that led to this successful PCV rollout. Methodology: A comprehensive desk review of both published and unpublished literature relevant to pneumonia burden and the efficacy and effectiveness of PCVs, along with documentation of PCV introduction and the scale-up was carried out. Results: The documentation of the PCV journey has been broken down into four sections: pre-introduction, PCV Phase-I introduction, pan-India rapid expansion, and the period post-introduction. Since the nationwide rollout in 2021, PCV coverage in India has steadily increased, reflecting successful immunization efforts. WUENIC, which is an annual WHO, and UNICEF estimates of national immunization coverage also show a positive trend in vaccination coverage (PCV booster coverage = 25% (2021), rising to 83% (2023), aligning with the goals of the WHO and UNICEF’s Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD). Conclusions: The phased rollout was an ambitious effort by the MoHFW, which was particularly challenging given the overlap with the COVID-19 pandemic. Despite these hurdles, the MoHFW, along with strong collaboration from development partners and stakeholders, successfully navigated the complex rollout. Future studies on the role of PCVs in reducing antibiotic resistance and the economic benefits of PCV introduction could help policymakers sustain funding and prioritize vaccine procurement decisions. Full article

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36 pages, 3120 KiB

Open AccessReview

Viral Infections in Elderly Individuals: A Comprehensive Overview of SARS-CoV-2 and Influenza Susceptibility, Pathogenesis, and Clinical Treatment Strategies

by Yanhao Huang, Shumin Li, Wenjie Ye, Haoyun Wang, Jun Su, Lijuan Gao, Ruohu Shi, Xinyi Mou, Sean Xiao Leng, Chanchan Xiao and Guobing Chen

Vaccines 2025, 13(4), 431; https://doi.org/10.3390/vaccines13040431 - 21 Apr 2025

Abstract

As age increases, the immune function of elderly individuals gradually decreases, increasing their susceptibility to infectious diseases. Therefore, further research on common viral infections in the elderly population, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, is crucial for scientific [...] Read more.

As age increases, the immune function of elderly individuals gradually decreases, increasing their susceptibility to infectious diseases. Therefore, further research on common viral infections in the elderly population, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, is crucial for scientific progress. This review delves into the genetic structure, infection mechanisms, and impact of coinfections with these two viruses and provides a detailed analysis of the reasons for the increased susceptibility of elderly individuals to dual viral infections. We evaluated the clinical manifestations in elderly individuals following coinfections, including complications in the respiratory, gastrointestinal, nervous, and cardiovascular systems. Ultimately, we have summarized the current strategies for the prevention, diagnosis, and treatment of SARS-CoV-2 and influenza coinfections in older adults. Through these studies, we aim to reduce the risk of dual infections in elderly individuals and provide a scientific basis for the prevention, diagnosis, and treatment of age-related viral diseases, thereby improving their health status. Full article

(This article belongs to the Special Issue A One-Health Perspective on Immunization Against Infectious Diseases)

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11 pages, 632 KiB

Open AccessArticle

Intranasal Sendai Virus Vaccination of Seropositive Children 1 to 2 Years of Age in a Phase I Clinical Trial Boosts Immune Responses Toward Human Parainfluenza Virus Type 1

by Elisabeth Adderson, Kim J. Allison, Kristen Branum, Robert E. Sealy, Bart G. Jones, Sherri L. Surman, Rhiannon R. Penkert, Randall T. Hayden, Charles J. Russell, Allen Portner, Karen S. Slobod and Julia L. Hurwitz

Vaccines 2025, 13(4), 430; https://doi.org/10.3390/vaccines13040430 - 19 Apr 2025

Abstract

Background/Objectives: Human parainfluenza virus type 1 (hPIV-1) is a major cause of serious respiratory diseases in young children. Annually, hPIV-1 results in approximately 10,000 hospitalizations in the United States due to croup, bronchiolitis, and/or pneumonia, and 10,000 deaths worldwide due to acute lower [...] Read more.

Background/Objectives: Human parainfluenza virus type 1 (hPIV-1) is a major cause of serious respiratory diseases in young children. Annually, hPIV-1 results in approximately 10,000 hospitalizations in the United States due to croup, bronchiolitis, and/or pneumonia, and 10,000 deaths worldwide due to acute lower respiratory tract infections among children less than 5 years of age. Despite the burden of disease, no vaccine for hPIV-1 is currently approved. Sendai virus (SeV) is a murine PIV-1. It has structural similarities with hPIV-1 and is currently under clinical development as an hPIV-1 Jennerian vaccine. Attributes of SeV include the following: (a) needleless delivery, (b) rapid and durable serum antibody responses after a single intranasal administration, (c) durable IgG and IgA responses in the nasal mucosa, and (d) use as a platform for recombinant vaccines against multiple pediatric pathogens. Evaluation of the tolerability, safety, and immunogenicity of intranasal SeV in healthy adults and seropositive children 3 to 6 years of age was previously conducted and supported vaccine advancement to evaluation in younger children. Methods: Three seropositive children 1 to 2 years of age received a single intranasal dose of 5 × 10⁵ EID₅₀ SeV (SENDAI, Clinicaltrials.gov NCT00186927). Adverse events were collected for 28 days post-vaccine administration using diary cards and participants were followed for six months in total. Sera were collected longitudinally for clinical laboratory and virus-specific antibody tests. Nasal swabs were collected longitudinally for virus and mucosal antibody tests. Results: Intranasal SeV was well tolerated, with only mild grade 1–2 events that resolved spontaneously. No serious adverse events, medically attended adverse events, or adverse events causing protocol termination were reported. One participant had positive nasal swabs for inoculated SeV during the first week after vaccination. Although children had measurable PIV-1-specific serum antibodies at baseline, intranasal SeV vaccination resulted in significant serum antibody increases in all participants. Similarly, there were significant increases in PIV-1-specific nasal IgG and IgA levels in all participants. Elevated antibody levels persisted through the six months of follow-up. Conclusions: Intranasal SeV was well tolerated and uniformly immunogenic in seropositive children 1 to 2 years of age. Results encourage the further evaluation of SeV and SeV-based recombinants as potential intranasal vaccines for the prevention of infection by hPIV-1 and other serious respiratory pathogens. Full article

(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)

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14 pages, 559 KiB

Open AccessReview

Intratumoral Immunotherapy in Breast Cancer

by Camille C. Baumrucker, Nicole Harris, Susan Hoover and Brian J. Czerniecki

Vaccines 2025, 13(4), 429; https://doi.org/10.3390/vaccines13040429 - 19 Apr 2025

Abstract

Breast cancer remains the most frequently diagnosed cancer and the second highest cause of cancer death in females. Metastatic recurrence that is resistant to traditional therapies presents a major challenge, necessitating the development of an innovative treatment strategy. Immunotherapy has gained popularity in [...] Read more.

Breast cancer remains the most frequently diagnosed cancer and the second highest cause of cancer death in females. Metastatic recurrence that is resistant to traditional therapies presents a major challenge, necessitating the development of an innovative treatment strategy. Immunotherapy has gained popularity in the treatment of cancer, particularly melanoma, lung cancer, and more recently breast cancer. Major developments in immunotherapy have been made with a better understanding of the tumor microenvironment and how the microenvironment can be manipulated to induce an anti-tumor immune response. Intratumorally delivered immunotherapy can be used to create a local immune response. This review provides a comprehensive overview of intratumoral immunotherapy for breast cancer and its resultant changes in the tumor microenvironment. The discussed immunotherapeutics include oncolytic viruses, nucleic acids, innate immune agonists, bacteria, chimeric antigen receptor T cells, and dendritic cells. The review also evaluates completed clinical trials using these therapies. Lastly, the review offers future perspectives in the development of breast cancer immunotherapy. Full article

(This article belongs to the Section Cancer Vaccines and Immunotherapy)

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20 pages, 2047 KiB

Open AccessArticle

Design and Preliminary Immunogenicity Evaluation of Nipah Virus Glycoprotein G Epitope-Based Peptide Vaccine in Mice

by Seungyeon Kim, Rochelle A. Flores, Seo Young Moon, Seung Yun Lee, Bujinlkham Altanzul, Jiwon Baek, Eun Bee Choi, Heeji Lim, Eun Young Jang, Yoo-kyoung Lee, In-Ohk Ouh and Woo H. Kim

Vaccines 2025, 13(4), 428; https://doi.org/10.3390/vaccines13040428 - 18 Apr 2025

Abstract

Background: The emergence of several paramyxoviruses, including Nipah virus (NiV), makes continued efforts in vaccine development as part of pandemic preparedness efforts necessary. Although NiV is a zoonotic pathogen with high case fatality, there is still no licensed vaccine. Methods: Herein, NiV attachment [...] Read more.

Background: The emergence of several paramyxoviruses, including Nipah virus (NiV), makes continued efforts in vaccine development as part of pandemic preparedness efforts necessary. Although NiV is a zoonotic pathogen with high case fatality, there is still no licensed vaccine. Methods: Herein, NiV attachment glycoprotein G (NiV-G), which is crucial to host cell receptor binding, was used to develop Nipah epitope-based peptide vaccines. A total of 39 B- and T-cell epitopes of NiV-G were shortlisted for peptide synthesis and evaluation using in silico analysis. Results: The in vitro antigenicity evaluation of the peptide candidates showed eight synthesized peptides (G7, stalk-domain epitopes) with relatively high binding to NiV-G antibody-positive serum (A_450nm: 1.39–3.78). Moreover, nine-mer (9-mer) peptides were found to be less reactive than their longer peptide counterparts (15–30 aa, G7-1, and G7-4), but 9-mer activity was enhanced with cyclization (NPLPFREYK, A_450nm: 2.66) and C-terminal amidation modification (NPLPFREYK-NH2, A_450nm: 1.39). Subsequently, in vivo validation in immunized mice revealed the immunogenicity potential of the G7-1 peptide vaccine (30 aa, NENVNEKCKFTLPPLKIHECNISCPNPLPF) to elicit a strong antigen-specific antibody response against their homologous peptide antigen (I.V., A_450nm: 1.48 ± 0.78; I.M., A_450nm: 1.66 ± 0.66). However, antibody binding to recombinant NiV-G protein remained low, suggesting limited recognition to the native antigen. Conclusions: This study focused on the preliminary screening and validation of peptide vaccines using single formulations with minimal modifications in the peptide candidates. Our findings collectively show the immunogenic potential of the NiV-G stalk-based epitope peptide vaccine as a novel therapeutic for NiV and underscores the need for strategic design, delivery, and formulation optimization to enhance its protective efficacy and translational application. Full article

(This article belongs to the Section Pathogens-host Immune Interface)

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