Vaccines

13 pages, 944 KiB

Open AccessReview

An In Vitro Approach to Prime or Boost Human Antigen-Specific CD8⁺ T Cell Responses: Applications to Vaccine Studies

by Hoang Oanh Nguyen, Mariela P. Cabral-Piccin, Victor Appay and Laura Papagno

Vaccines 2025, 13(7), 729; https://doi.org/10.3390/vaccines13070729 (registering DOI) - 4 Jul 2025

Although vaccine development has primarily focused on inducing neutralizing antibodies, increasing evidence supports an important role of CD8⁺ T cell responses in vaccine effectiveness. Routine assays, which are mainly based on antibody titers, may therefore not accurately reflect the full immune response [...] Read more.

Although vaccine development has primarily focused on inducing neutralizing antibodies, increasing evidence supports an important role of CD8⁺ T cell responses in vaccine effectiveness. Routine assays, which are mainly based on antibody titers, may therefore not accurately reflect the full immune response elicited by vaccination. Assessing antigen-specific T cell responses upon vaccination poses several challenges. A common issue in studying T cells specific to a vaccine antigen is their low frequency in circulation, which can limit their ex vivo analysis. Moreover, the use of human cell-based models is crucial for studying and optimizing the induction of T cell responses to design effective vaccines. We developed an innovative in vitro approach of human CD8⁺ T cell priming, based on the rapid mobilization of dendritic cells (DCs) directly from unfractionated peripheral blood mononuclear cells (PBMCs). This simple and original method allows for side-by-side comparisons of multiple test parameters in a standardized system, providing both quantitative and qualitative readouts of primed antigen-specific CD8⁺ T cells. Here, we discuss the genesis of this approach and its versatile applications, including monitoring antigen-specific T cell responses, evaluating an individual’s T cell priming capacity, and conducting preclinical studies on potential adjuvants and vaccine candidates. Full article

(This article belongs to the Special Issue Analysis of Vaccine-Induced Adaptive Immune Responses)

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16 pages, 665 KiB

Open AccessArticle

Vaccination Reduces Fecal Shedding and Improves Carcass Quality in Pigs with Subclinical Lawsonia intracellularis Infections

by Rubén Del Pozo Sacristán, Hanny Swam, Stephan von Berg and Amy Elizabeth Taylor

Vaccines 2025, 13(7), 728; https://doi.org/10.3390/vaccines13070728 - 4 Jul 2025

Abstract

Background/Objectives: Lawsonia intracellularis is a bacterium that causes Proliferative Enteropathy, an enteric infection characterized mainly by diarrhea and growth retardation, leading to important economic losses. Acute and chronic infections are easily diagnosed, and their control by vaccination has been proven efficacious. However, [...] Read more.

Background/Objectives: Lawsonia intracellularis is a bacterium that causes Proliferative Enteropathy, an enteric infection characterized mainly by diarrhea and growth retardation, leading to important economic losses. Acute and chronic infections are easily diagnosed, and their control by vaccination has been proven efficacious. However, subclinical infections, despite being very prevalent, often remain underdiagnosed and uncontrolled in practice. Scarce research is available on the control of subclinical infections by vaccination, and the benefit in these scenarios remains to be elucidated. Two field trials were carried out to (1) determine the association between the growth and fecal shedding of L. intracellularis in unvaccinated and intramuscularly vaccinated pigs in a farm with subclinical infection and (2) assess the impact of intradermal vaccination against L. intracellularis on clinical performance and carcass quality in a herd with subclinical infection. Methods: A pig herd with subclinical infection was selected. Pigs were vaccinated intramuscularly (study 1) or intradermally (study 2) at weaning. Fecal shedding, performance, clinical parameters, and carcass quality were investigated. Results: Growth was negatively associated with the fecal load of L. intracellularis in non-vaccinated pigs, whereas in vaccinated pigs, growth performance was not impacted by fecal load (study 1). Vaccinated pigs presented a significantly lower fecal load, lower prevalence of tail biting (31.7%) compared with controls (54.2%), less back fat, and a greater Lean Meat percentage (study 2). Conclusions: Vaccination against L. intracellularis in a herd with subclinical infection and low fecal bacterial shedding led to a reduction in fecal shedding, a lower prevalence of tail biting, and an improvement in carcass quality. Full article

(This article belongs to the Special Issue Swine Vaccines and Vaccination)

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24 pages, 732 KiB

Open AccessReview

Advances in Oncolytic Viral Therapy in Melanoma: A Comprehensive Review

by Ayushi Garg, Rohit Rao, Felicia Tejawinata, Gazi Amena Noor Shamita, McKay S. Herpel, Akihiro Yoshida, Gordon Goolamier, Jessica Sidiropoulos, Iris Y. Sheng, Salim-Tamuz Abboud, Luke D. Rothermel, Nami Azar and Ankit Mangla

Vaccines 2025, 13(7), 727; https://doi.org/10.3390/vaccines13070727 - 3 Jul 2025

Abstract

Checkpoint inhibitor therapy revolutionized the treatment of patients with melanoma. However, in patients where melanoma exhibits resistance to checkpoint inhibitor therapy, the treatment options are limited. Oncolytic viruses are a unique form of immunotherapy that uses live viruses to infect and lyse tumor [...] Read more.

Checkpoint inhibitor therapy revolutionized the treatment of patients with melanoma. However, in patients where melanoma exhibits resistance to checkpoint inhibitor therapy, the treatment options are limited. Oncolytic viruses are a unique form of immunotherapy that uses live viruses to infect and lyse tumor cells to release the elusive neoantigen picked up by the antigen-presenting cells, thus increasing the chances of an immune response against cancer. Coupled with checkpoint inhibitors, intratumoral injections of the oncolytic virus can help an enhanced immune response, especially in a tumor that displays resistance to checkpoint inhibitors. However, oncolytic viruses are not bereft of challenges and face several obstacles in the tumor microenvironment. From the historical use of wild viruses to the sophisticated use of genetically modified viruses in the current era, oncolytic virus therapy has evolved tremendously in the last two decades. Increasing the ability of the virus to select the malignant cells over the non-malignant ones, circumventing the antiviral immune response from the body, and enhancing the oncolytic properties of the viral platform by attaching various ligands are some of the several improvements made in the last three decades. In this manuscript, we trace the journey of the development of oncolytic virus therapy, especially in the context of melanoma. We review the clinical trials of talimogene laherparepvec in patients with melanoma. We also review the data available from the clinical trials of vusolimogene oderparepvec in patients with melanoma. Finally, we review the use of various oncolytic viruses and their challenges in clinical development. This manuscript aims to create a comprehensive literature review for clinicians to understand and implement oncolytic virus therapy in patients diagnosed with melanoma. Full article

(This article belongs to the Special Issue Next-Generation Vaccine and Immunotherapy)

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11 pages, 538 KiB

Open AccessArticle

COVID-19 Vaccine Response in Allo-HSCT Recipients: Insights from a Real-World Prospective Cohort Study

by Emine Merve Savaş, Şeyma Yıldız, Zübeyde Nur Özkurt, Zehra Baltacı, Özlem Güzel Tunçcan, Zeynep Arzu Yeğin, Kayhan Çağlar, Nurdan Köktürk, Gonca Erbaş, Gülendam Bozdayı and Münci Yağcı

Vaccines 2025, 13(7), 726; https://doi.org/10.3390/vaccines13070726 - 3 Jul 2025

Abstract

Background: Allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients are still at increased risk of severe COVID-19 infection. Vaccination is a critical strategy to protect this population. This real-world prospective cohort study aimed to evaluate the immune response and clinical outcomes of COVID-19 vaccines [...] Read more.

Background: Allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients are still at increased risk of severe COVID-19 infection. Vaccination is a critical strategy to protect this population. This real-world prospective cohort study aimed to evaluate the immune response and clinical outcomes of COVID-19 vaccines in Allo-HSCT recipients. Methods: Allo-HSCT recipients (median age: 48 years) who received either the BNT162b2 or CoronaVac vaccines were included. Antibodies against the SARS-CoV-2 spike protein were quantitatively measured using the chemiluminescent microparticle immunoassay. Patient- and vaccine-related factors affecting antibody responses were analyzed. Adverse events, including graft-versus-host disease (GVHD) and post-vaccine infections, were recorded. Results: Among 95 Allo-HSCT recipients, 86.3% achieved adequate antibody responses following COVID-19 vaccination. Patients receiving ≥3 vaccine doses showed significantly higher antibody titers compared to those with only 2 doses (OR: 0.11; 95% CI: 0.02–0.53; p = 0.006 **). The use of Ruxolitinib or Ibrutinib was associate with increased odds of low antibody response (OR: 38.39; 95% CI: 3.14–468.95; p = 0.004 **). Hypogammaglobulinemia (low serum IgG levels) was associated with a reduced antibody response (OR: 0.17; 95% CI: 0.03–0.96; p = 0.045 *), while no significant correlation was found between serum IgA levels and antibody responses (p = 0.672). Three cases of post-vaccine GVHD were observed, and no fatalities related to COVID-19 occurred during the study. Conclusions: COVID-19 vaccination is safe and effective in Allo-HSCT recipients, with stronger responses especially following ≥3 vaccine doses. Patients receiving GVHD treatment or with hypogammaglobulinemia exhibited impaired responses, emphasizing the need for tailored vaccination strategies and close monitoring in this population. Full article

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

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26 pages, 2069 KiB

Open AccessReview

Unraveling Helicobacter pylori: Insights into Pathogenesis, Immune Evasion, and Progress Toward Effective Vaccination

by Ayman Elbehiry, Eman Marzouk and Adil Abalkhail

Vaccines 2025, 13(7), 725; https://doi.org/10.3390/vaccines13070725 - 3 Jul 2025

Abstract

Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections globally, significantly contributing to gastritis, peptic ulcers, and gastric malignancies. Its pathogenesis involves a complex array of virulence factors—including cagA, vacA, and urease—which facilitate mucosal colonization, [...] Read more.

Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections globally, significantly contributing to gastritis, peptic ulcers, and gastric malignancies. Its pathogenesis involves a complex array of virulence factors—including cagA, vacA, and urease—which facilitate mucosal colonization, immune evasion, and persistent inflammation. A major challenge in vaccine development is the bacterium’s ability to manipulate both innate and adaptive immune responses, resulting in limited natural clearance and long-term persistence. This review synthesizes H. pylori pathogenesis and host immune dynamics, highlighting their implications for vaccine design. By elucidating the molecular and cellular mechanisms underlying host–pathogen interactions, we explore how these insights inform antigen selection, adjuvant optimization, and delivery strategies. By integrating basic science with translational objectives, this review aims to support the development of an effective H. pylori vaccine, addressing global health needs, particularly in regions with a high infection burden and limited access to treatment. Full article

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

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20 pages, 2293 KiB

Open AccessArticle

An Evaluation of the Safety, Immunogenicity, and Protective Efficacy of a Combined Diphtheria–Tetanus–Acellular Pertussis, Haemophilus influenzae Type b, and ACYW135 Meningococcal Conjugate Vaccine in Murine and Rat Models

by Xiuwen Sui, Zhujun Shao, Yuanyuan Ji, Hairui Wang, Qingfu Xu, Bochao Wei, Zhuojun Duan, Chang Wang, Ying Yang, Jiayu Zhao and Tao Zhu

Vaccines 2025, 13(7), 724; https://doi.org/10.3390/vaccines13070724 - 3 Jul 2025

Abstract

Background: The combined diphtheria–tetanus–acellular pertussis (three-component), Haemophilus influenzae type b (Hib, conjugate), and ACYW135 meningococcal (conjugate) vaccine (DTaP-Hib-MCV4) offers a promising alternative to single-component vaccines, potentially simplifying immunization schedules and improving vaccination coverage. Methods: We evaluated the safety, immunogenicity, and protective [...] Read more.

Background: The combined diphtheria–tetanus–acellular pertussis (three-component), Haemophilus influenzae type b (Hib, conjugate), and ACYW135 meningococcal (conjugate) vaccine (DTaP-Hib-MCV4) offers a promising alternative to single-component vaccines, potentially simplifying immunization schedules and improving vaccination coverage. Methods: We evaluated the safety, immunogenicity, and protective efficacy of DTaP-Hib-MCV4 in animal models. Acute and long-term toxicity studies were conducted in Sprague-Dawley (SD) rats with equal numbers of male and female animals. Immunogenicity was assessed in female NIH mice and SD rats using a three-dose regimen at 14-day intervals. Orbital blood was collected 14 days post-immunization to measure IgG titers against pertussis, diphtheria, tetanus, Hib, and meningococcal antigens. The protective efficacy was determined using potency tests for the pertussis, diphtheria, and tetanus components; passive protection studies for Hib; and serum bactericidal antibody (SBA) titers against A/C/Y/W135 meningococcal serogroups. Results: Acute and repeated-dose toxicity studies in SD rats showed no signs of abnormal toxicity or irritation at either high (three doses/rat) or low (one dose/rat) doses levels. The no-observed-adverse-effect level (NOAEL) for DTaP-Hib-MCV4 was established at three doses/rat after 8 weeks of repeated intramuscular administration and a 4-week recovery period. Specific IgG antibodies against all the vaccine components were detected in animal sera at both one and three doses/rat, with no evidence of immunotoxicity. Following two-dose primary immunization in murine models, the combined vaccine elicited robust antigen-specific antibody responses, with geometric mean titers (GMTs) as follows: 1,280,000 for pertussis toxin (PT); 761,093 for filamentous hemagglutinin (FHA); 1,159,326 for pertactin (PRN); 1,659,955 for diphtheria toxoid (DT); 1,522,185 for tetanus toxoid (TT); 99 for Haemophilus influenzae type b (Hib); and 25,600, 33,199, 8300, and 9051 for serogroups A, C, Y, and W135 of Neisseria meningitidis, respectively. In the rat models, three-dose primary immunization also elicited robust antigen-specific antibody responses. Protection studies demonstrated efficacy against pertussis, tetanus toxin, and diphtheria toxin challenges. In the Hib challenge study, none of the 10 animals given anti-DTaP-Hib-MCV4 antiserum developed bacteremia after the live Hib challenge (vs. 5814/0.1 mL in the negative control, p < 0.001). In addition, the SBA titers against meningococcal serogroups exceeded the protective threshold (≥1:8) in 92.2% of the immunized mice and 100% of the immunized rats. Crucially, the combined vaccine induced potent immune responses and protective efficacy, with antibody levels and protection against each component antigen comparable to or greater than those of the individual components: DTaP, Hib, and MCV4. Conclusions: These findings demonstrate that the DTaP-Hib-MCV4 combined vaccine is both safe and immunogenic, supporting its potential as a viable alternative to individual vaccines. This combined vaccine may streamline immunization programs and enhance vaccination coverage. Full article

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23 pages, 939 KiB

Open AccessReview

Kidney Involvement in SARS-CoV-2 Infection: Peritoneal Dialysis as the Preferred Modality

by Marko Baralić, Nikola Stojanović, Selena Gajić, Aleksandar Sič, Aarish Manzar, Ana Bontić, Jelena Pavlović, Mateja N. Bojić and Aleksandra Kezić

Vaccines 2025, 13(7), 723; https://doi.org/10.3390/vaccines13070723 - 2 Jul 2025

Abstract

Patients undergoing peritoneal dialysis (PD) represent a uniquely vulnerable population due to intrinsic immunological dysfunction and a high prevalence of comorbid conditions. This review examines the complex interplay between natural and vaccine-induced immune responses to SARS-CoV-2 in this group, focusing on viral entry, [...] Read more.

Patients undergoing peritoneal dialysis (PD) represent a uniquely vulnerable population due to intrinsic immunological dysfunction and a high prevalence of comorbid conditions. This review examines the complex interplay between natural and vaccine-induced immune responses to SARS-CoV-2 in this group, focusing on viral entry, immune activation, and immune evasion mechanisms. Particular attention is given to the impaired cellular and humoral responses seen in PD patients, including reduced T-cell function, diminished antibody production, and abnormal cytokine signaling, all of which contribute to an elevated risk of severe COVID-19 outcomes. The immunogenicity and clinical efficacy of various vaccine platforms, including inactivated, vector-based, and mRNA formulations, are critically assessed, with an emphasis on the role of booster doses in enhancing protection amid waning immunity and evolving viral variants. Furthermore, the review highlights the advantages of PD as a home-based modality that is compatible with telemedicine and may reduce the risk of viral exposure. These insights underscore the importance of developing individualized vaccination strategies, maintaining close immunological surveillance, and implementing innovative dialysis care approaches to improve clinical outcomes during the ongoing pandemic and future public health crises. Tailored booster strategies and telemedicine-integrated care models are essential for improving outcomes in this high-risk population. Full article

(This article belongs to the Special Issue Immune Responses in Patients with Chronic Disease After Vaccination)

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16 pages, 328 KiB

Open AccessArticle

Evaluation of Anti-HPV18 Antibody Titers Preceding an Incident Cervical HPV18/45 Infection

by Fanua Wiek, Viswanathan Shankar, Ana Gradissimo, Angela Diaz, Ligia A. Pinto, Nicolas F. Schlecht and Robert D. Burk

Vaccines 2025, 13(7), 722; https://doi.org/10.3390/vaccines13070722 - 2 Jul 2025

Abstract

Background: The Human Papillomavirus (HPV) vaccine generates high antibody titers against targeted HPV types. This study investigated vaccine-induced anti-HPV18 immunoglobulin (IgG) antibody titers and subsequent HPV18/45 infections. Methods: We performed a nested matched case-control study leveraging a prospective longitudinal cohort of adolescent and [...] Read more.

Background: The Human Papillomavirus (HPV) vaccine generates high antibody titers against targeted HPV types. This study investigated vaccine-induced anti-HPV18 immunoglobulin (IgG) antibody titers and subsequent HPV18/45 infections. Methods: We performed a nested matched case-control study leveraging a prospective longitudinal cohort of adolescent and young adult women (AYW) vaccinated with the quadrivalent HPV vaccine (4vHPV) attending the Mount Sinai Adolescent Health Center (MSAHC) in Manhattan, NY. The case individuals included AYW who had an incident detection of cervical HPV18 (n = 3) or HPV45 (n = 34) DNA after vaccination and were compared to two vaccinated control individuals (HPV18/45-negative); one random control (RC, n = 37) and one high-risk control (HRC, n = 37) selected from the upper quartile of a sexual risk behavior score. Serological titers against HPV18 were measured by end-point dilution and enzyme-linked immunosorbent assay (ELISA) in serum collected before the incident detection of HPV. Matching was performed based on age at first dose, follow-up time, and sexual risk behavior score. Conditional logistic regression was used to assess the association between case-control status and anti-HPV antibody titers, consistent with the matched-pair design. Results: Antibody titers for HPV18 were most different between AYW who developed an HPV18/45 infection compared to high-risk controls OR = 1.66, 95% CI: 0.96–2.85 (p = 0.1629). Analyses of pooled data from vaccinated recipients including who developed HPV16/31 or HPV18/45 infections demonstrated that the odds of a one-log unit increase in anti-HPV16 or 18 antibody titers, respectively, were 40% higher in the combined control groups (RC + HRC, n = 160) (OR = 1.40, 95% CI: 1.09–1.79, p = 0.0135) and 73% higher in the HRC (n = 80) (OR 1.73, 95% CI: 1.34, 2.52, p = 0.0117) compared to HPV16/18/31/45 cases (n = 80). Conclusions: Overall, these findings suggest that higher IgG antibodies to HPV16/18 after vaccination represent an increased likelihood of protection from homologous and cross-reactive HPV types (HPV16/18/31/45). These results show that differences in antibody titers are associated with breakthrough infection after vaccination, suggesting that further study of long-term antibody titers and infection should be pursued. Full article

(This article belongs to the Special Issue Prevention of Human Papillomavirus and Vaccines Strategies)

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13 pages, 3523 KiB

Open AccessArticle

Simple and High-Throughput Quantification of Mono- and Bivalent Foot-and-Mouth Disease Virus Vaccine Antigens by Differential Scanning Fluorimetry

by Yanli Yang, Xiaojie Chen, Ming Li, Fei Xin, Yi Zhao, Chengfeng Zhang, Yiping Pan, Chuanyu He and Sun He

Vaccines 2025, 13(7), 721; https://doi.org/10.3390/vaccines13070721 - 2 Jul 2025

Abstract

Background/Objectives: An accurate quantification of the effective antigens from different serotypes is essential for the quality control of multivalent vaccines, but it remains challenging. Herein, we developed a simple and high-throughput method using differential scanning fluorimetry (DSF) for quantifying foot-and-mouth disease virus (FMDV) [...] Read more.

Background/Objectives: An accurate quantification of the effective antigens from different serotypes is essential for the quality control of multivalent vaccines, but it remains challenging. Herein, we developed a simple and high-throughput method using differential scanning fluorimetry (DSF) for quantifying foot-and-mouth disease virus (FMDV) antigens in monovalent and bivalent vaccines. Methods: Purified serotypes A and O FMDV were used to establish and validate the method. The DSF parameters, including the dye concentration, thermal scanning velocity, and PCR tube material, were optimized at different FMDV concentrations. The established DSF method was validated for the quantification of monovalent and A/O bivalent FMDV, and was compared with the ultracentrifugation of 86 samples from different processing stages and serotypes. Results: The DSF showed that the melting temperature (T_m) of type A (56.2 °C) was significantly higher than that of type O FMDV (50.5 °C), indicating that their T_m can be distinguished in bivalent antigens. After optimizing the DSF parameters, a strong correlation (R² > 0.998) was observed between the 146S concentration and the maximum of the first derivative of the DSF fluorescence (d(RFU)/dT) for both serotypes A and O FMDV. The method demonstrated good reproducibility (RSD < 10%) and high sensitivity (limit of detection: 0.7 μg/mL). Using a multiple linear regression analysis, the simultaneous quantification of A and O FMDV in the bivalent mixtures achieved recovery rates of 82.4–105.5%, with an RSD < 10% for most of the samples. Additionally, the DSF results correlated well with the ultracentrifugation data (Pearson ρ = 0.9789), validating its accuracy and broad applicability. Conclusions: In summary, DSF represents a simple, rapid, and high-throughput tool for the quality control of monovalent and bivalent FMDV vaccines. Full article

(This article belongs to the Section Veterinary Vaccines)

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4 pages, 156 KiB

Open AccessEditorial

Vaccines and Vaccination: Feature Papers

by Pedro Plans-Rubió

Vaccines 2025, 13(7), 720; https://doi.org/10.3390/vaccines13070720 - 1 Jul 2025

Abstract

This Special Issue, entitled “Vaccines and vaccination: Feature Papers”, included articles that addressed various issues related to vaccines and vaccination, including studies assessing interventions to increase vaccination coverage [...] Full article

(This article belongs to the Special Issue Vaccines and Vaccination: Feature Papers)

12 pages, 329 KiB

Open AccessArticle

Enablers and Barriers of COVID-19 Vaccination in the Philippines

by Evalyn Roxas, Paulyn Jean Acacio-Claro, Maria Margarita Lota, Alvin Abeleda, Soledad Natalia Dalisay, Madilene Landicho, Yoshiki Fujimori, Jan Zarlyn Rosuello, Jessica Kaufman, Margaret Danchin, Vicente Belizario, Jr. and Florian Vogt

Vaccines 2025, 13(7), 719; https://doi.org/10.3390/vaccines13070719 - 1 Jul 2025

Abstract

Background: The COVID-19 pandemic prompted extensive vaccination efforts globally, yet in the Philippines, many families remained unvaccinated. Caregivers are key decision-makers for family vaccination, but evidence on factors influencing their own vaccine uptake is limited. Methods: A cross-sectional survey of primary [...] Read more.

Background: The COVID-19 pandemic prompted extensive vaccination efforts globally, yet in the Philippines, many families remained unvaccinated. Caregivers are key decision-makers for family vaccination, but evidence on factors influencing their own vaccine uptake is limited. Methods: A cross-sectional survey of primary caregivers was conducted in low COVID-19 vaccine uptake regions in the Philippines from July to October 2023 using a validated questionnaire. Multivariable logistic regression identified enablers and barriers to vaccine uptake. Results: Among 775 respondents, 72.3% completed primary vaccination, 3.3% had incomplete vaccination, and 24.4% were unvaccinated. Key factors for vaccination included self, family, and community protection, and the influence of government regulations. Distrust in vaccine safety was the main barrier. Positive associations with vaccine uptake were found for age [30–45 years (aOR = 2.23) and 46–59 years (aOR = 2.84)], education [secondary (aOR = 2.25) and tertiary (aOR = 4.93)], and employment (aOR = 1.99). Confidence in vaccine safety (aOR = 1.92), vaccine effectiveness (aOR = 2.23), and satisfaction with vaccination efforts (aOR = 2.39) were additional enablers. Disagreement with restrictions on the unvaccinated was a barrier (aOR = 0.31). Conclusions: This study identified multiple factors influencing COVID-19 vaccination among primary caregivers in low uptake areas of the Philippines. Interventions addressing perceptions about vaccine safety and effectiveness, particularly among younger and less educated caregivers, may improve public trust and satisfaction with vaccination efforts. Full article

(This article belongs to the Special Issue Promoting Research, Development and Access to Vaccines to Address Global Inequities)

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27 pages, 5667 KiB

Open AccessArticle

Pre-Vaccination Immune Profiles and Responsiveness to Innate Stimuli Predict Reactogenicity and Antibody Magnitude Following mRNA Vaccination

by Amanda E. Zelkoski, Emilie Goguet, Emily Samuels Darcey, Mohamad-Gabriel Alameh, Hooda Said, Simon Pollett, John H. Powers III, Eric D. Laing, Cara Olsen, Edward Mitre and Allison M. W. Malloy

Vaccines 2025, 13(7), 718; https://doi.org/10.3390/vaccines13070718 - 1 Jul 2025

Abstract

Background: While mRNA vaccines effectively limit hospitalization and severe COVID-19 disease, the precise early innate immune mechanisms associated with their efficacy and reactogenicity remain underexplored. The identification of innate immune correlates prior to vaccination could provide mechanistic insights and potentially predict responses. Methods: [...] Read more.

Background: While mRNA vaccines effectively limit hospitalization and severe COVID-19 disease, the precise early innate immune mechanisms associated with their efficacy and reactogenicity remain underexplored. The identification of innate immune correlates prior to vaccination could provide mechanistic insights and potentially predict responses. Methods: We developed an in vitro model to study the innate immune activation of pre-vaccination peripheral blood mononuclear cells (PBMCs) collected from participants enrolled in a well-characterized COVID-19 BioNTech/Pfizer BNT162b2 vaccine (BNT162b2 vaccine) cohort. Pre-vaccination PBMCs were stimulated with empty lipid nanoparticle (LNP), mRNA-LNP, or Toll-like receptor (TLR) agonists. Using multiparameter spectral flow cytometry, we analyzed the baseline immune state, innate responsiveness to stimuli, and cytokine profiles of study participants. These pre-vaccination in vitro results were analyzed for correlations with post-vaccination symptoms and spike-specific IgG responses. Results: Baseline dendritic cell (DC) states inversely correlated with the magnitude of symptoms following BNT162b2 vaccination. Heightened conventional (cDC) and weaker plasmacytoid DC (pDC) responses to RNA stimuli correlated with the magnitude of an acute IgG response. IgG durability modestly correlated with a lower pDC state but higher cDC2 and monocyte baseline states and inversely correlated with TLR3 agonist responsiveness. Conclusions: The pre-vaccination assessment of innate immune function and resting states can be used to fit models potentially predictive of immunogenicity and reactogenicity to BNT162b2 vaccination. Pre-vaccination DC states may influence reactogenicity, while the response to RNA may impact antibody responses. Our data suggest that pre-vaccination assessment offers insights into the innate mechanisms driving mRNA vaccine responses and has predictive potential. Full article

(This article belongs to the Section Nucleic Acid (DNA and mRNA) Vaccines)

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12 pages, 631 KiB

Open AccessReview

Challenges and Limitations of Current RSV Prevention Strategies in Infants and Young Children: A Narrative Review

by Nicola Principi, Serafina Perrone and Susanna Esposito

Vaccines 2025, 13(7), 717; https://doi.org/10.3390/vaccines13070717 - 1 Jul 2025

Abstract

Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal [...] Read more.

Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal immunization. While these interventions have improved early protection, several limitations hinder their broader impact and long-term effectiveness. Methods: This narrative review synthesizes evidence from clinical trials, observational studies, and regulatory reports to evaluate the main limitations of nirsevimab and maternal RSV vaccination. Literature searches were conducted in major databases, focusing on efficacy, safety, immunogenicity, implementation, and population-specific challenges. Results: Both nirsevimab and maternal vaccination provide strong protection during the first six months of life, but their effectiveness wanes thereafter. This is concerning as nearly half of RSV-related deaths occur in children over six months old. Maternal vaccine efficacy is uncertain in very-preterm infants, and safety concerns persist, including potential associations with preterm birth, Guillain–Barré syndrome, and hypertensive disorders. Real-world data from low-income countries are lacking, limiting generalizability. Additionally, the risk of vaccine-associated enhanced disease (VAED), although unconfirmed, has delayed pediatric vaccine development. Emerging monoclonal antibodies and live-attenuated vaccines are under investigation to extend protection beyond infancy. Conclusions: Despite substantial progress, current RSV prevention strategies leave critical gaps, particularly for older infants and underserved populations. There is a pressing need for next-generation vaccines, enhanced pharmacovigilance, and equitable global implementation to ensure sustained and inclusive RSV protection. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)

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13 pages, 461 KiB

Open AccessArticle

How Immunization Information Systems Inform Age-Based HPV Vaccination Recommendations in the United States: A Mixed-Methods Study

by Nadja A. Vielot, Isabelle K. Bucklin, Kristy Westfall, Deanna Kepka, Gregory Zimet and Sherri Zorn

Vaccines 2025, 13(7), 716; https://doi.org/10.3390/vaccines13070716 - 30 Jun 2025

Abstract

Background: Immunization information systems (IISs) in the United States forecast vaccine due dates, which can inform when providers recommend vaccines to patients. IIS forecasting for HPV vaccination at 9 years, the minimum age of licensure, and when vaccination is likely most effective [...] Read more.

Background: Immunization information systems (IISs) in the United States forecast vaccine due dates, which can inform when providers recommend vaccines to patients. IIS forecasting for HPV vaccination at 9 years, the minimum age of licensure, and when vaccination is likely most effective is not documented or well-understood. Methods: We documented characteristics of HPV vaccination forecasts in jurisdictional IISs through Internet searches and requests to immunization program managers. Next, we conducted focus groups with stakeholders from seven jurisdictions to elucidate their processes for determining and implementing HPV vaccination forecasts. Results: Forecast data were available from 49 out of 64 CDC-funded jurisdictions, of which 14 (29%) recommended HPV vaccination at age 9 and 35 (71%) recommended HPV vaccination starting at ages 11 through to 15. Jurisdictions that recommended HPV vaccination at age 9 cited the positions of the American Cancer Society and American Academy of Pediatrics and reported little or no provider opposition to this recommendation. Jurisdictions reported variable flexibility in programming their forecasts. Those that changed their HPV vaccination forecast from 11 to 9 years did so easily while some experienced limitations. Other jurisdictions adhered strictly to the CDC’s routine recommendation at age 11–12 years and would only update the forecast in tandem with updated CDC guidance. The impact of IISs and electronic health record interoperability on how providers view and utilize IIS forecasting is unclear. Conclusions: Jurisdictions can share best practices for forecasting at 9 and future studies can evaluate the effects of forecasting age on the vaccination rates, providing evidence for nationwide vaccination recommendations. Full article

(This article belongs to the Special Issue Improving HPV Vaccination Coverage: Current Issues, Future Prospects and Strategies)

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18 pages, 1853 KiB

Open AccessSystematic Review

Safety, Immunogenicity, and Efficacy of COVID-19 Vaccines in Radiation–Oncology Patients: A Systematic Review and Meta-Analysis

by Paul Thöne, Margot Egger, Michael Stephan Gruber, Georg Gruber, Christina Kasassov, Dalma Nyiri, Eva Weis, Helene Werl, Leonhard Trinkl, Wolfgang Lilleby, Martin Clodi, Elisabeth Bräutigam, Benjamin Dieplinger, Annette Aigner and Hans Geinitz

Vaccines 2025, 13(7), 715; https://doi.org/10.3390/vaccines13070715 - 30 Jun 2025

Abstract

Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current [...] Read more.

Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current evidence on COVID-19 vaccination in patients undergoing radiotherapy (RT). Methods: PubMed, Livivo, Scopus, and Cochrane Library were systematically reviewed for relevant publications on COVID-19 vaccination in the context of radiation oncology, published by 19 April 2024. The treatment effects were calculated as the proportion of seroconverted individuals. Results: A total of 22 studies published between 2021 and 2024 were included, covering various aspects of vaccination, including safety, tolerability, qualitative and quantitative humoral responses, cellular responses, vaccination efficacy, and booster vaccinations. Notably, patients undergoing RT exhibited a high willingness to receive vaccination. Vaccination was overall well tolerated and safe, with a low incidence of side effects, which were primarily mild. The primary meta-analysis showed a seroconversion proportion of 91% [95% CI: 84–96%] overall, with a somewhat higher proportion of 93% in patients receiving RT alone, compared to 90% in patients receiving either RT or RT combined with chemotherapy. Furthermore, immunization during RT led to a sustained increase in antibody titers, with a notable long-term persistence of IgG. Conclusions: COVID-19 vaccines demonstrate excellent safety, immunogenicity, and efficacy in patients receiving RT, who also exhibit a high willingness to be vaccinated. The outcomes observed are comparable to those in healthy controls and superior to those seen in patients receiving other cancer treatments, such as chemotherapy. The vaccination of radiation oncology patients in future pandemics or epidemics is strongly advocated even during active treatment. Full article

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

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18 pages, 13905 KiB

Open AccessArticle

Replication of Vectored Herpesvirus of Turkey (HVT) in a Continuous, Microcarrier-Independent Suspension Cell Line from Muscovy Duck

by Karoline Mähl, Deborah Horn, Sirine Abidi, Benedikt B. Kaufer, Volker Sandig, Alexander Karlas and Ingo Jordan

Vaccines 2025, 13(7), 714; https://doi.org/10.3390/vaccines13070714 - 30 Jun 2025

Abstract

Background/Objectives: More than 33 billion chickens are industrially raised for meat and egg production globally and vaccinated against Marek’s disease virus (MDV). The antigenically related herpesvirus of turkey (HVT) is used as a live-attenuated vaccine, commonly provided as a recombinant vector to protect [...] Read more.

Background/Objectives: More than 33 billion chickens are industrially raised for meat and egg production globally and vaccinated against Marek’s disease virus (MDV). The antigenically related herpesvirus of turkey (HVT) is used as a live-attenuated vaccine, commonly provided as a recombinant vector to protect chickens against additional unrelated pathogens. Because HVT replicates in a strictly cell-associated fashion to low levels of infectious units, adherent primary chicken or duck embryo fibroblasts are infected, dislodged from the cultivation surface and distributed as cryocultures in liquid nitrogen to the site of application. Although viable cells are complex products, application of infected cells in ovo confers protection even in presence of maternal antibodies. Methods/Results: The aim of our study was to determine whether a continuous cell line in a scalable cultivation format can be used for production of HVT-based vaccines. The AGE1.CR cell line (from Muscovy duck) was found to be highly permissive in adherent cultures. Propagation in suspension, however, initially gave very low yields. The induction of cell-to-cell contacts in carrier-independent suspensions and a metabolic shock improved titers to levels suitable for vaccine production (>10⁵ infectious units/mL after infection with multiplicity of 0.001). Conclusions: Production of HVT is challenging to scale to large volumes and the reliance on embryonated eggs from biosecure facilities is complex. We demonstrate that a cell-associated HVT vector can be propagated in a carrier-independent suspension culture of AGE1.CR cells in chemically defined medium. The fed-batch production is independent of primary cells and animal-derived material and can be scaled to large volumes. Full article

(This article belongs to the Special Issue Animal Herpesviruses: 2nd Edition)

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24 pages, 312 KiB

Open AccessArticle

Social Ecological Influences on HPV Vaccination Among Cape Verdean Immigrants in the U. S.: A Qualitative Study

by Ana Cristina Lindsay, Celestina V. Antunes, Aysha G. Pires, Monica Pereira and Denise L. Nogueira

Vaccines 2025, 13(7), 713; https://doi.org/10.3390/vaccines13070713 - 30 Jun 2025

Abstract

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal, [...] Read more.

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal, particularly among racial, ethnic, and immigrant minority groups. This study explored multiple factors, such as cultural, social, and structural influences, influencing HPV vaccine decision-making among Cape Verdean immigrant parents in the U.S., a population currently underrepresented in HPV research. Methods: Qualitative study using individual, in-depth interviews with Cape Verdean immigrant parents of children aged 11 to 17 years living in the U.S. Interviews were transcribed verbatim and analyzed thematically using the social ecological model (SEM) to identify barriers and facilitators at the intrapersonal, interpersonal, organizational, community, and policy levels. Results: Forty-five Cape Verdean parents (27 mothers, 18 fathers) participated. Fathers were significantly older than mothers (50.0 vs. 41.1 years, p = 0.05). Most were married or partnered (60%), had at least a high school education (84.4%), and reported annual household incomes of US$50,000 or more (66.7%), with no significant gender differences. Nearly all spoke Creole at home (95.6%). Fathers had lower acculturation than mothers (p = 0.05), reflecting less adaptation to U.S. norms and language use. Most parents had limited knowledge of HPV and the vaccine, with gendered beliefs and misconceptions about risk. Only seven mothers (25.9%) reported receiving a provider recommendation; all indicated that their children had initiated vaccination (1 dose or more). Mothers were the primary decision-makers, though joint decision-making was common. Trust in providers was high, but poor communication and the lack of culturally and linguistically appropriate materials limited informed decision-making. Stigma, misinformation, and cultural taboos restricted open dialogue. Trusted sources of information included schools, churches, and Cape Verdean organizations. While parents valued the U.S. healthcare system, they noted gaps in public health messaging and provider engagement. Conclusions: Findings revealed that HPV vaccine uptake and hesitancy among Cape Verdean immigrant parents in the U.S. were influenced by individual beliefs, family dynamics, healthcare provider interactions, cultural norms, and structural barriers. These findings highlight the need for multilevel strategies such as culturally tailored education, community engagement, and improved provider communication to support informed vaccination decisions in this population. Full article

(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers: 2nd Edition)

14 pages, 1084 KiB

Open AccessArticle

Adverse Events and Associated Economic Burden of COVID-19 Vaccination in Queensland, Australia: Findings from the Cross-Sectional QoVAX-Statewide Study

by Qing Xia, Kerry-Ann F. O’Grady, Peter Vardon, Selina Ward, Rebecca Gregory, Janet Davies and Hannah E. Carter

Vaccines 2025, 13(7), 712; https://doi.org/10.3390/vaccines13070712 - 30 Jun 2025

Abstract

Background/Objectives: The economic impact of adverse events following COVID-19 immunisation (AEFIs) in Australia is underexplored. This study aimed to assess the economic burden of AEFIs on both healthcare systems and societal productivity. Methods: A cross-sectional survey was conducted in Queensland residents [...] Read more.

Background/Objectives: The economic impact of adverse events following COVID-19 immunisation (AEFIs) in Australia is underexplored. This study aimed to assess the economic burden of AEFIs on both healthcare systems and societal productivity. Methods: A cross-sectional survey was conducted in Queensland residents aged ≥18 years who had received at least one dose of a COVID-19 vaccine in the preceding 12 months. Overall, 6964 participants were recruited from July to September 2022 via email and broad social media campaigns. The survey collected data on the incidence, type and duration of AEFIs; healthcare utilisation; and work-related absenteeism. Healthcare costs were estimated using national healthcare reimbursement data, and productivity costs were estimated using Australian Bureau of Statistics Average Weekly Earnings. Results: Of the 6797 eligible respondents (predominantly female [62%]; median age: 52 years), AEFIs were reported by 53.4%, 44.1%, 40.7%, and 40.9% following doses 1 to 4, respectively. Pain and tenderness were predominant local AEFIs, while tiredness and headaches were the most frequent systemic AEFIs, generally resolving within three days. Relatively few participants reporting AEFIs consulted medical professionals: 7.0%, 7.3%, 5.1%, and 1.9% following each dose, respectively. The mean healthcare cost per person reporting AEFIs was AUD 24, AUD 88, AUD 22, and AUD 4 following each respective dose. Work absenteeism was recorded in 16.5%, 18.2%, 15.2%, and 11.2% following each dose with mean absenteeism days per person of 4.7, 7.4, 3.6 and 2.1, respectively, and mean productivity costs per person reporting AEFIs amounting to AUD 1494, AUD 2388, AUD 1136, and AUD 690, respectively. Conclusions: Participants reported mostly mild AEFIs with only a small proportion of individuals seeking medical services. Productivity costs attributable to these AEFIs exceeded direct healthcare expenses incurred. Full article

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

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15 pages, 2074 KiB

Open AccessArticle

Measles Epidemiology and Coverage of Immunization Against Measles in the Autonomous Province of Vojvodina, Serbia: Local Trends in a Regional Context

by Mioljub Ristić, Svetlana Ilić, Smiljana Rajčević, Mirjana Štrbac, Snežana Medić, Tatjana Pustahija, Vladimir Vuković, Marko Koprivica, Gorana Dragovac and Vladimir Petrović

Vaccines 2025, 13(7), 711; https://doi.org/10.3390/vaccines13070711 - 30 Jun 2025

Abstract

Background: Despite ongoing global elimination efforts, measles remains a persistent public health threat. Methods: This retrospective observational study examines trends in crude measles incidence and vaccination coverage from 1948 to 2024 in the northern region of Serbia—Autonomous Province of Vojvodina (AP Vojvodina)—which accounts [...] Read more.

Background: Despite ongoing global elimination efforts, measles remains a persistent public health threat. Methods: This retrospective observational study examines trends in crude measles incidence and vaccination coverage from 1948 to 2024 in the northern region of Serbia—Autonomous Province of Vojvodina (AP Vojvodina)—which accounts for 26.9% of the national population. This study further explores measles vaccination coverage across the province’s seven districts, along with the number of reported measles cases, age distribution, and vaccination status of affected individuals from 2000 to 2024. Data were obtained from official annual immunization records maintained by public health institutions within the framework of Serbia’s national mandatory immunization program. Results: A notable resurgence of measles occurred in Serbia during 2017–2018, following a decline in vaccination coverage. In AP Vojvodina, outbreaks were recorded in 2007, 2014–2015, and 2017–2018, predominantly affecting unvaccinated children and adults aged 20–39 years. Since 2019, the measles incidence has significantly declined. During the 2018 outbreak, the highest incidence was observed among children aged 1–4 years (40.6 per 100,000), followed by infants under 1 year (17.3 per 100,000) and adults aged 20–39 years (12.5 per 100,000). An analysis of the data from 2000 to 2024 revealed substantial age- and dose-related differences in measles incidence, particularly among unvaccinated individuals, those who had received one or two doses of a measles-containing vaccine (MCV), and those with unknown vaccination status. During the 2017–2018 epidemic, unvaccinated children under 1 year and those aged 1–4 years were the most affected. A marked increase in cases among single-dose recipients was noted in 2018, especially in adults aged 20–39 years (9.5%) and those ≥40 years (13.5%). A considerable proportion of measles cases in these age groups had unknown vaccination status: 33.1% among individuals aged 20–39 years and 18.2% among those aged ≥ 40 years. Epidemiological investigation linked the 2007 and 2014–2015 outbreaks in AP Vojvodina to importations from Bosnia and Herzegovina. No specific source was identified for the 2017–2018 outbreak, suggesting possible endemic transmission. Conclusions: These findings underscore the impact of fluctuating vaccination coverage on measles resurgence. Sustaining high two-dose MCV coverage, strengthening routine immunization programs, enhancing surveillance systems, and ensuring timely outbreak preparedness are critical measures for achieving effective measles control. Full article

(This article belongs to the Special Issue Epidemiology of Diseases Preventable by Vaccination)

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