Vaccines

14 pages, 925 KiB

Open AccessArticle

Safety and Immunogenicity of a 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) in Chinese Children, Adults and the Elderly: A Phase 4, Randomized, Double-Blind, Active-Controlled Clinical Trial

by Xiaoyu Liu, Gang Shi, Yuanyuan Dong, Wanqi Yang, Yinan Wang, Xianying Ye, Juxiang Zhang, Xinyi Yang, Dan Yu, Dan Song, Yuehong Ma, Zeng Wang, Hong Li and Weijun Hu

Vaccines 2025, 13(8), 866; https://doi.org/10.3390/vaccines13080866 - 15 Aug 2025

Abstract

Objectives: This randomized, double-blind, active-controlled non-inferiority phase 4 clinical trial was conducted to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) compared to an active comparator vaccine. Methods: Pneumococcal vaccine-naïve participants aged ≥2 years were randomly assigned in a [...] Read more.

Objectives: This randomized, double-blind, active-controlled non-inferiority phase 4 clinical trial was conducted to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) compared to an active comparator vaccine. Methods: Pneumococcal vaccine-naïve participants aged ≥2 years were randomly assigned in a 2:1 ratio to receive a single dose of either the investigational vaccine (n = 1199) or the comparator vaccine (n = 600). Immunogenicity was evaluated at baseline and 30 days post-vaccination by measuring serotype-specific IgG antibodies against all 23 pneumococcal serotypes using enzyme-linked immunosorbent assay. The primary outcome was seroconversion, defined as a ≥two-fold increase in serotype-specific IgG antibody titers at day 30 compared to baseline. Results: At one month post-vaccination, seroconversion rates for each of the 23 serotypes ranged from 59.22% to 95.67% in the treatment group, compared to 59.66% to 94.07% in the control group. Non-inferiority was demonstrated for all serotypes, with the lower bounds of the 95% confidence intervals (95%CI) for rate differences exceeding the predefined −10% margin. Moreover, superiority was observed for 12 serotypes (6B, 23F, 1, 2, 4, 8, 9N, 9V, 11A, 15B, 17F and 18C), as the lower bounds of their 95%CI for rate differences were above 0. Adverse reactions were reported in 236 (19.68%) participants of the investigational group and 118 (19.67%) of the control group within 30 days post-vaccination, with no significant differences between groups. Conclusions: The PPSV23 vaccine administered among individual aged ≥2 years was safe, well tolerated and immunogenic, eliciting an immune response either comparable to or higher than control vaccine. These findings support its use as a safe and effective option for pneumococcal immunization. Full article

(This article belongs to the Special Issue Safety and Immunogenicty of Vaccination)

► Show Figures

Figure 1

17 pages, 1623 KiB

Open AccessArticle

Accelerating Neoantigen Discovery: A High-Throughput Approach to Immunogenic Target Identification

by Lena Pfitzer, Gitta Boons, Lien Lybaert, Wim van Criekinge, Cedric Bogaert and Bruno Fant

Vaccines 2025, 13(8), 865; https://doi.org/10.3390/vaccines13080865 - 15 Aug 2025

Abstract

Background: Antigen-targeting immunotherapies hinge on the accurate identification of immunogenic epitopes that elicit robust T-cell responses. However, current computational approaches focus primarily on MHC binding affinity, leading to high false-positive rates and limiting the clinical utility of antigen selection methods. Methods: [...] Read more.

Background: Antigen-targeting immunotherapies hinge on the accurate identification of immunogenic epitopes that elicit robust T-cell responses. However, current computational approaches focus primarily on MHC binding affinity, leading to high false-positive rates and limiting the clinical utility of antigen selection methods. Methods: We developed the neoIM (for “neoantigen immunogenicity”) model, a first-in-class, high-precision immunogenicity prediction tool that overcomes these limitations by focusing exclusively on overall CD8 T-cell response rather than MHC binding. neoIM, a random forest classifier, was trained solely on MHC-presented non-self peptides (n = 61.829). Its performance was assessed against that of currently existing alternatives on several in vitro immunogenicity datasets. In addition, its clinical impact was investigated in two retrospective analyses of clinical trial data by assessing the effect of neoIM-based antigen selection on the positive immunogenicity rate of personal vaccine designs. Finally, the potential for neoIM as a biomarker was investigated by assessing the correlation between neoIM scores and overall survival in a melanoma patient cohort treated with checkpoint inhibitors (CPI). Results: neoIM was found to substantially outperform publicly available tools in regards to in vitro benchmarks based on ELISpot assays, with an increase in predictive power of at least 30%, reducing false positives and improving target selection efficiency. In addition, using neoIM scores during patient-specific antigen prioritization and selection was shown to yield up to 50% more clinically actionable antigens for individual patients in two recent clinical trials. Finally, we showed that neoIM could further refine response prediction to checkpoint inhibition therapy, further demonstrating the importance of evaluating neoantigen immunogenicity. Conclusions: These findings establish neoIM as the first computational tool capable of accurately predicting epitope immunogenicity beyond MHC affinity. By enabling more precise target discovery and prioritization, neoIM has the potential to accelerate the development of next-generation antigen-based immunotherapies. Full article

(This article belongs to the Special Issue Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives)

► Show Figures

Figure 1

26 pages, 3208 KiB

Open AccessArticle

Efficacy of Three Vaccine Regimens Against Infectious Hematopoietic Necrosis Virus Transmission Potential in Rainbow Trout

by Juliette Doumayrou, Mary G. Frazier, Hannah N. Brown and Andrew R. Wargo

Vaccines 2025, 13(8), 864; https://doi.org/10.3390/vaccines13080864 - 15 Aug 2025

Abstract

Background: Vaccination is often a highly effective approach for protecting against clinical disease and mortality caused by viruses. However, vaccine efficacy against viral transmission has rarely been assessed, which can provide vital information on the eradication efficacy and sustainability of vaccines in the [...] Read more.

Background: Vaccination is often a highly effective approach for protecting against clinical disease and mortality caused by viruses. However, vaccine efficacy against viral transmission has rarely been assessed, which can provide vital information on the eradication efficacy and sustainability of vaccines in the field. Methods: Here, we evaluated the host mortality, shedding, and direct fish-to-fish transmission protection efficacy of three vaccine regimens (DNA, inactivated, and attenuated) against infectious hematopoietic necrosis virus (IHNV) in rainbow trout. We quantified protection against single- and mixed-genotype IHNV infections when the vaccines were delivered by intramuscular injection, intraperitoneal injection, and bath immersion, respectively, to reflect field conditions. Results: All three vaccine regimens provided significant protection against fish mortality. The DNA vaccine regimen was qualitatively the most protective and the attenuated vaccine regimen the least. However, these three vaccines provided limited protection against viral shedding. Cumulative shedding over the course of the infection was only slightly reduced compared to unvaccinated fish. There was some indication that the viral genotype fish were exposed to influenced vaccine efficacy, perhaps as a result of genetic similarity to the vaccine strain. Likewise, the DNA vaccine reduced direct transmission in fish cohabitation experiments from 100% to 50%. The inactivated and attenuated vaccine had little impact on IHNV transmission. Conclusions: Collectively, our results suggest that existing IHNV vaccines that increase host survival provide minimal virus transmission protection in rainbow trout, which is likely to limit their long-term efficacy in the field. This work contributes to a growing body of evidence that enhancement of the transmission protection of IHNV and other vaccines will likely bolster disease reduction in the field. Full article

(This article belongs to the Section Veterinary Vaccines)

► Show Figures

Graphical abstract

25 pages, 376 KiB

Open AccessReview

Research Progress of Universal Influenza Vaccine

by Liangliang Wang, Qian Xie, Pengju Yu, Jie Zhang, Chenchen He, Weijin Huang, Youchun Wang and Chenyan Zhao

Vaccines 2025, 13(8), 863; https://doi.org/10.3390/vaccines13080863 - 15 Aug 2025

Abstract

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza [...] Read more.

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza vaccines and their advantages and disadvantages in universal vaccine design. We also summarize the common design strategies for universal influenza vaccines, which mainly include the immunofocusing strategy, multi-target combination strategy, T-cell strategy, computationally optimized broadly cross-reactive antigenic strategy (COBRA), and artificial intelligence strategy. In addition, we also sort out the latest research progress of universal influenza vaccines under different technological routes. This will help researchers better grasp the latest developments of universal influenza vaccines. Full article

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

12 pages, 833 KiB

Open AccessArticle

Efficacy of Heterologous Vaccination Using Virus-Like Particles and Vaccinia Virus Containing MIC8 and AMA1 Proteins of Toxoplasma gondii

by Hae-Ji Kang and Fu-Shi Quan

Vaccines 2025, 13(8), 862; https://doi.org/10.3390/vaccines13080862 - 15 Aug 2025

Abstract

Background: Toxoplasma gondii (T. gondii) infection causes serious diseases in immunocompromised patients and causes congenital toxoplasmosis in infants. T. gondii microneme protein 8 (MIC8) and apical membrane antigen 1 (AMA1) are essential proteins involved in parasitic invasion. Methods: In this [...] Read more.

Background: Toxoplasma gondii (T. gondii) infection causes serious diseases in immunocompromised patients and causes congenital toxoplasmosis in infants. T. gondii microneme protein 8 (MIC8) and apical membrane antigen 1 (AMA1) are essential proteins involved in parasitic invasion. Methods: In this study, we generated virus-like particles (VLPs) and recombinant vaccinia virus (rVV) containing MIC8 or AMA1 proteins. Vaccine efficacy was evaluated in mice (BALB/c) upon challenge infection with T. gondii ME49. Results: Intramuscular immunization with heterologous vaccines (rVV + VLPs; rVV for prime and VLPs for boost) elicited T. gondii-specific IgG antibody responses in mice. Four weeks after the boost, all mice were orally challenged with T. gondii ME49, and protective immunity was assessed. The responses of antibody-secreting cells for IgG2a and IgG2b and those of memory B cells and CD4+ and CD8+ T cells were higher in the rVV + VLP group than in the VLP + VLP group. The rVV + VLP group exhibited a significant reduction in cyst count in the brain. Conclusions: These findings indicate that heterologous vaccination with vaccinia viruses and VLPs improves vaccine efficacy. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)

► Show Figures

Figure 1

15 pages, 856 KiB

Open AccessReview

Rural–Urban Disparities in COVID-19 Vaccine Uptake and Associated Mortality and Cardiovascular Disease Outcomes in the United States

by Bailey Smith, Fahad Farakh, Asma Hanif, Javed H Tunio and Shumaila Nida Javed Tunio

Vaccines 2025, 13(8), 861; https://doi.org/10.3390/vaccines13080861 - 14 Aug 2025

Abstract

Background: The COVID-19 pandemic magnified long-standing health disparities in the United States, particularly among rural, disadvantaged populations. These communities experience greater barriers to healthcare access, a higher prevalence of chronic illness, and increased vaccine hesitancy factors that collectively contribute to poorer health outcomes. [...] Read more.

Background: The COVID-19 pandemic magnified long-standing health disparities in the United States, particularly among rural, disadvantaged populations. These communities experience greater barriers to healthcare access, a higher prevalence of chronic illness, and increased vaccine hesitancy factors that collectively contribute to poorer health outcomes. Methods: This narrative review examines rural–urban disparities in COVID-19 vaccine uptake and their impact on mortality, with a focus on cardiovascular disease (CVD) outcomes. We synthesized the peer-reviewed literature, CDC data, and U.S. Census reports to assess factors contributing to vaccine hesitancy, vaccination coverage, COVID-19-related mortality, and CVD mortality trends. Results: Rural residents were less likely to initiate COVID-19 vaccination, showed greater vaccine hesitancy, and experienced higher rates of both COVID-19 and CVD mortality. These disparities were further driven by safety concerns surrounding mRNA technology, misinformation, infrastructural barriers, and sociodemographic factors including political affiliation, education, poverty, and religion. Notably, pre-existing CVD increased vulnerability to severe COVID-19 outcomes in rural communities. Conclusions: Expanding vaccination efforts and improving healthcare infrastructure are essential for addressing these widening health inequities. Future public health strategies should prioritize culturally tailored interventions and rural-specific outreach to reduce vaccine hesitancy and improve mortality outcomes in underserved populations. Full article

(This article belongs to the Special Issue COVID-19 Vaccination and Public Health: Addressing Global, Regional and Within-Country Inequalities)

► Show Figures

Figure 1

20 pages, 973 KiB

Open AccessReview

New Vaccine Introduction in Middle-Income Countries Across the Middle East and North Africa—Progress and Challenges

by Chrissy Bishop, Deeksha Parashar, Diana Kizza, Motuma Abeshu, Miloud Kaddar, Abdallah Bchir, Atef El Maghraby, Hannah Schirrmacher, Zicheng Wang, Ulla Griffiths, Shahira Malm, Sowmya Kadandale and Saadia Farrukh

Vaccines 2025, 13(8), 860; https://doi.org/10.3390/vaccines13080860 - 14 Aug 2025

Abstract

Background/Objectives: The middle-income countries (MICs) in the Middle East and North Africa (MENA) region face multifaceted challenges—including fiscal constraints, conflict, and vaccine hesitancy—that impede the timely introduction of critical vaccines. This study examines the status, barriers, and facilitators to introducing three critical [...] Read more.

Background/Objectives: The middle-income countries (MICs) in the Middle East and North Africa (MENA) region face multifaceted challenges—including fiscal constraints, conflict, and vaccine hesitancy—that impede the timely introduction of critical vaccines. This study examines the status, barriers, and facilitators to introducing three critical vaccines—human papillomavirus vaccine (HPV), pneumococcal conjugate vaccine (PCV), and rotavirus vaccine (RV)—across seven MENA MICs, to identify actionable solutions to enhance vaccine uptake and immunisation coverage. Methods: Using the READ methodology (ready materials, extract, analyse, and distil data), this review systematically analysed policy documents, reports, and the literature on the introduction of HPV, PCV, and RV vaccines in seven MENA MICs. A data extraction framework was designed to capture the status of vaccine introduction and barriers and facilitators to introduction. Findings and data gaps were validated with stakeholder consultations. Results: Of the seven study countries, progress in introducing PCV and RV has been uneven across the region (five countries have introduced PCV, four have introduced RV, and only a single country has introduced HPV at time of writing), hindered by vaccine hesitancy, fiscal challenges, and insufficient epidemiological data. Morocco is the only country to introduce all three vaccines, while Egypt has yet to introduce any. Other common barriers include the impact of conflict and displacement on healthcare infrastructure, delayed introduction due to the 2020 COVID-19 pandemic, and limited local production facilities and regional cooperation. In addition, not all countries eligible for Gavi MICs support have applied. These findings provide a roadmap for policymakers to accelerate equitable vaccine introduction in the MENA region. Conclusions: Targeted efforts, such as addressing fiscal constraints, improving local manufacturing, tackling gender barriers, and fostering public trust, paired with regional collaboration, can help bridge gaps and ensure no community is left behind in preventing vaccine-preventable diseases. Full article

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

► Show Figures

Figure 1

13 pages, 1290 KiB

Open AccessSystematic Review

Immunogenicity as a Predictor of Influenza Vaccine Efficacy: A Systematic Review

by André Miguel Martins, Luis Félix Valero Juan, Marlene Santos and João P. Martins

Vaccines 2025, 13(8), 859; https://doi.org/10.3390/vaccines13080859 - 14 Aug 2025

Abstract

Background/Objectives: Influenza represents a significant burden on global public health, and vaccination is the most effective strategy to reduce it. The large investment in vaccination programs and the need for adjustments in vaccine serotypes are important reasons for evaluating the influenza vaccine’s efficacy [...] Read more.

Background/Objectives: Influenza represents a significant burden on global public health, and vaccination is the most effective strategy to reduce it. The large investment in vaccination programs and the need for adjustments in vaccine serotypes are important reasons for evaluating the influenza vaccine’s efficacy every year. Establishing a relationship between immunogenicity data and efficacy is also crucial for predicting the efficacy of a vaccine during its development. Antibody response measurement is one of the most common methods for evaluating immunogenicity, particularly in vaccines and biologics. The aim of this systematic review was to define a model that relates the immunogenicity of a given vaccine to its efficacy, based on hemagglutination inhibition titer levels. Methods: To achieve this goal, information was gathered from articles linking immunogenicity with the efficacy of the influenza vaccine in the Medline and Scopus databases. Different mathematical models were developed and applied to assess the relationship between HAI titers and the effectiveness of the flu vaccine. This analysis was conducted for the various existing vaccines, for the different influenza virus strains, and for their efficacy in paediatric populations. Results: The r² obtained ranged from 0.2579 to 0.966, which points to the importance of this immunological factor in the efficacy of the influenza vaccine. Conclusions: The efficacy values for titer level 40 confirm the validity of the data provided by Hobson. Full article

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

► Show Figures

Figure 1

20 pages, 8252 KiB

Open AccessArticle

Evaluation of Cross-Protection of African Swine Fever Vaccine ASFV-G-ΔI177L Between ASFV Biotypes

by Manuel V. Borca, Elizabeth Ramirez-Medina, Christine Mutisya, Rose Ojuok, Josiah Odaba, Mark Dihbol, Anna Lacasta and Douglas P. Gladue

Vaccines 2025, 13(8), 858; https://doi.org/10.3390/vaccines13080858 - 13 Aug 2025

Abstract

Background/Objectives: Vaccine development for the prevention of ASF has been very challenging due to the extensive genetic and largely unknown antigenic diversity. Inactivated vaccines, using different inactivation methods and a variety of adjuvants, have been consistently inefficacious. Historically, animals recovering from an infection [...] Read more.

Background/Objectives: Vaccine development for the prevention of ASF has been very challenging due to the extensive genetic and largely unknown antigenic diversity. Inactivated vaccines, using different inactivation methods and a variety of adjuvants, have been consistently inefficacious. Historically, animals recovering from an infection with an attenuated virus became protected from the development of a clinical disease caused by an antigenically related strain. Therefore, immunization of susceptible animals with attenuathe ted virus strains has become a common method of vaccination with the first two commercially available vaccines based on recombinant live-attenuated viruses (LAVs). An important limitation is that the efficacy of the LAV is restricted to those strains that are antigenically related and, in most cases, only provide protection against homologous strains. Due to the unknown antigenic heterogeneity among all ASFV field isolates, the development of broad-spectrum vaccines is a challenge. Besides the anecdotal data, there is not a large amount of information describing patterns of cross-protection between different ASFV strains. Methods: We evaluated the cross-protection induced by the ASFV live-attenuated vaccine ASFV-G-ΔI177L against different biotypes of ASFV and compared their genomic sequences to determine potential genetic mutations that could cause the lack of cross-protection. Results: Results presented here demonstrate different patterns of protection when ASFV-G-ΔI177L vaccinated pigs were challenged with six different ASFV field isolates belonging to different biotypes. Conclusions: The presence of cross-protection cannot be predicted solely by the classical methodology for genotyping-based B646L ORF only. Biotyping, considering the entire virus proteome, appears to be a more promising prediction tool, although additional gathering of experimental data will be necessary to fully validate it; until then, the presence of cross-protection needs to be confirmed in efficacy trials challenging vaccinated animals. Full article

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

► Show Figures

Figure 1

19 pages, 3631 KiB

Open AccessArticle

Biological Characterization and DIVA Potential of Three Rough Brucella melitensis Vaccine Strains

by Jinyue Liu, Yi Yin, Xinmei Yang, Mengsi Li, Jing Qu, Shaohui Wang, Yanqing Bao, Jingjing Qi, Tonglei Wu and Mingxing Tian

Vaccines 2025, 13(8), 857; https://doi.org/10.3390/vaccines13080857 - 13 Aug 2025

Abstract

Background: Brucellosis is a zoonotic bacterial disease primarily controlled through quarantine, culling, and vaccination. Live attenuated vaccines remain the most effective countermeasure, yet their application is limited by residual virulence and diagnostic interference. This study developed three rough-type attenuated Brucella melitensis mutants (G7, [...] Read more.

Background: Brucellosis is a zoonotic bacterial disease primarily controlled through quarantine, culling, and vaccination. Live attenuated vaccines remain the most effective countermeasure, yet their application is limited by residual virulence and diagnostic interference. This study developed three rough-type attenuated Brucella melitensis mutants (G7, G8, G16) and evaluated their potential as DIVA (Differentiating Infected from Vaccinated Animals) vaccine candidates. Methods: Rough phenotypes were characterized through heat agglutination, acridine orange staining, and immunoblotting. Macrophage cytotoxicity was assessed via LDH release assays, while RT-qPCR analyzed macrophage activation capacity. Mouse infection and immunization-challenge experiments, complemented by histopathology, evaluated residual virulence and protective immunity. Antibody profiles were determined by ELISA, and DIVA capability was verified using LPS-coated ELISA. Results: G7 and G8 exhibited complete rough phenotypes, whereas G16 retained partial O-antigen (semi-rough). All rough mutants induced macrophage cytotoxicity and activation. The strains showed attenuated virulence with no viable bacteria recovered from spleens at 4 weeks post-inoculation. Histopathology revealed no liver lesions at 6 weeks post-inoculation. Immunized mice predominantly produced IgG2a-dominated Th1-type responses. The immune protection levels of G7 and G16 matched the reference vaccine M5–90Δ26, while G8 showed slightly lower efficacy. LPS-ELISA effectively differentiated vaccinated from infected animals via concurrent IgM/IgG detection. Conclusions: This study demonstrates that the rough-type B. melitensis mutants G7 and G16 serve as promising DIVA vaccine candidates, offering strong protection with low residual virulence while enabling serological differentiation between vaccinated and infected animals, highlighting their potential as effective vaccines for brucellosis control. Full article

(This article belongs to the Special Issue Bacterial and Viral Infections: Current Challenges and Vaccine Innovations)

► Show Figures

Figure 1

14 pages, 880 KiB

Open AccessReview

Toll-like Receptor (TLR) Response in Chikungunya Virus Infection: Mechanism of Activation, Immune Evasion, and Use of TLR Agonists in Vaccine Development

by Mohammad Enamul Hoque Kayesh, Michinori Kohara and Kyoko Tsukiyama-Kohara

Vaccines 2025, 13(8), 856; https://doi.org/10.3390/vaccines13080856 - 13 Aug 2025

Abstract

CHIKV is a re-emerging mosquito-borne arthritogenic alphavirus associated with large outbreaks and severe joint pain, and it poses a growing global health threat. Toll-like receptors (TLRs), as key pattern recognition receptors, detect viral components and initiate antiviral immune responses. Increasing evidence highlights the [...] Read more.

CHIKV is a re-emerging mosquito-borne arthritogenic alphavirus associated with large outbreaks and severe joint pain, and it poses a growing global health threat. Toll-like receptors (TLRs), as key pattern recognition receptors, detect viral components and initiate antiviral immune responses. Increasing evidence highlights the role of TLR signaling in shaping CHIKV infection outcomes, though its precise contribution remains unclear. CHIKV has developed mechanisms to evade host innate immune surveillance, promoting viral replication. TLR agonists show promise as vaccine adjuvants by enhancing immune responses. In this review, we summarize current insights into TLR-mediated immunity during CHIKV infection, the virus’s innate immune evasion strategies, and the potential of TLR agonists in improving vaccine efficacy. Full article

(This article belongs to the Special Issue The Immunology of Dengue, Chikungunya and Zika Virus: Implications for Vaccines and Vaccine Development)

► Show Figures

Figure 1

25 pages, 3253 KiB

Open AccessReview

Multisystem Endothelial Inflammation: A Key Driver of Adverse Events Following mRNA-Containing COVID-19 Vaccines

by János Szebeni and Akos Koller

Vaccines 2025, 13(8), 855; https://doi.org/10.3390/vaccines13080855 - 12 Aug 2025

Abstract

mRNA-LNP-based COVID-19 vaccines, namely Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, were successfully deployed to help control the SARS-CoV-2 pandemic, and their updated formulations continue to be recommended, albeit only for high-risk populations. One widely discussed aspect of these vaccines is their uniquely broad spectrum [...] Read more.

mRNA-LNP-based COVID-19 vaccines, namely Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, were successfully deployed to help control the SARS-CoV-2 pandemic, and their updated formulations continue to be recommended, albeit only for high-risk populations. One widely discussed aspect of these vaccines is their uniquely broad spectrum and increased incidence of adverse events (AEs), collectively referred to as post-vaccination syndrome (PVS). Although the reported PVS rate is low, the high number of administered doses among healthy individuals has resulted in a substantial number of reported vaccine-related injuries. A prominent manifestation of PVS is multisystem inflammation, hypothesized to result from the systemic transfection of organ cells with genetic instructions for a toxin, the spike protein, delivered with lipid nanoparticles (LNPs). In this narrative review, we focus on endothelial cells in the microcirculatory networks of various organs as primary sites of transfection with mRNA-LNP and consequent PVS. We outline the anatomical variations in the microcirculation contributing to the individual variability of symptoms and examine the molecular and cellular responses to vaccine nanoparticle exposure at the endothelial cell level with a focus on the pathways of a sustained cascade of toxic and autoimmune processes. A deeper understanding of the mechanisms underlying mRNA-LNP-induced AEs and PVS at the organ and cellular levels is critical for improving the safety of future vaccines and other therapeutic applications of this groundbreaking technology. Full article

(This article belongs to the Special Issue Population Immunity and Persistence to SARS-CoV-2 Induced by Infection and Vaccination, Protection Against New Infections and Implication for Further Vaccination: 2nd Edition)

► Show Figures

Figure 1

18 pages, 2170 KiB

Open AccessArticle

VVX001 Induces preS-Specific Antibodies Reacting to Common HBV Genotypes in Hepatitis B Virus (HBV) Carrier Mice

by Inna Tulaeva, Maryline Bourgine, Carolin Cornelius-Nikl, Alexander Karaulov, Rainer Henning, Marie-Louise Michel and Rudolf Valenta

Vaccines 2025, 13(8), 854; https://doi.org/10.3390/vaccines13080854 - 12 Aug 2025

Abstract

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain [...] Read more.

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB. Full article

(This article belongs to the Special Issue Role of Next Generation Vaccines in Immunotherapeutics)

► Show Figures

Figure 1

23 pages, 1964 KiB

Open AccessReview

Freeze-Drying of mRNA-LNPs Vaccines: A Review

by MD Faizul Hussain Khan, Floriane Baudin, Ayyappasamy Sudalaiyadum Perumal and Amine A. Kamen

Vaccines 2025, 13(8), 853; https://doi.org/10.3390/vaccines13080853 - 12 Aug 2025

Abstract

The instability of mRNA vaccines presents significant challenges for their storage, transportation, and large-scale distribution, particularly in resource-limited countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving mRNA vaccine efficacy. This formulation technique enhances the long-term stability of mRNA [...] Read more.

The instability of mRNA vaccines presents significant challenges for their storage, transportation, and large-scale distribution, particularly in resource-limited countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving mRNA vaccine efficacy. This formulation technique enhances the long-term stability of mRNA vaccines by converting them into a stable dry powder. The purpose of this review is to provide an overview of the current knowledge on the progress of freeze-drying techniques for mRNA vaccines, with emphasis on the associated challenges. This review highlights the factors influencing the stability of freeze-dried mRNA vaccines and provides a comprehensive overview of the formulation components, including excipients, buffers, and surfactants, as well as the process parameters and storage conditions that aim to improve stability and shelf-life. By providing these insights, this review supports the advancement of more robust, scalable, and efficient lyophilization protocols, ultimately addressing the stability limitations of mRNA vaccines and enhancing their global accessibility. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

► Show Figures

Figure 1

21 pages, 763 KiB

Open AccessSystematic Review

Humoral and Cellular Immune Responses Against SARS-CoV-2 Following COVID-19 Vaccination in Older Adults: A Systematic Review

by Ruth Angélica Rojas-De la Cruz, Janeth M. Flores-Córdova, Cielo Cinthya Calderon-Hernandez, Nelson Luis Cahuapaza-Gutierrez, Nino Arturo Ccallalli-Ruiz and Fernando M. Runzer-Colmenares

Vaccines 2025, 13(8), 852; https://doi.org/10.3390/vaccines13080852 - 12 Aug 2025

Abstract

Background: Evidence on the humoral and cellular immune responses to SARS-CoV-2 following COVID-19 vaccination in older adults is warranted. Aims: To synthesize and analyze the current evidence on humoral and cellular immune responses to both standard and booster COVID-19 vaccination in individuals aged [...] Read more.

Background: Evidence on the humoral and cellular immune responses to SARS-CoV-2 following COVID-19 vaccination in older adults is warranted. Aims: To synthesize and analyze the current evidence on humoral and cellular immune responses to both standard and booster COVID-19 vaccination in individuals aged 60 years and older. Methods: Clinical trials and observational studies were included. Reviews, case series, letters to the editor, and similar publications were excluded. A selective literature search was conducted in the following databases: PubMed, Scopus, EMBASE, and Web of Science. The risk of bias and methodological quality of the included studies were assessed using the Newcastle–Ottawa Scale (NOS) and the Risk of Bias 2.0 (RoB 2) tool. Statistical analysis was conducted using Stata version 18 and Review Manager version 5.4.1. Results: Thirteen studies were included: eleven observational studies and two randomized clinical trials, evaluating humoral and cellular immune responses in 782 older adults. Messenger RNA vaccines were the most administered, particularly Pfizer-BioNTech (76.9%) and Moderna mRNA-1273 (23%). In most cases, immune responses were assessed after the second dose and booster doses. Most studies (61.5%) reported increased IgG titers specific to the SARS-CoV-2 Spike protein, while 23.1% reported a decrease. Regarding cellular immunity, 46.2% of the studies reported low interferon-gamma (IFN-γ) levels post-vaccination, whereas 38.5% showed increases. These findings highlight the need for tailored vaccination strategies to address emerging variants, particularly in vulnerable populations such as older adults. Conclusions: In older adults receiving COVID-19 vaccination, humoral immunity tends to increase, whereas cellular responses are frequently diminished, reflecting age-related immunosenescence that may limit the durability and breadth of protection following vaccination in older adults. Full article

(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)

► Show Figures

Figure A1

14 pages, 2099 KiB

Open AccessArticle

Immunogenicity and Protective Efficacy of a Recombinant Toxoplasma gondii GRA12 Vaccine in Domestic Cats

by Jinru Yang, Linchong Nie, Yining Song, Zipeng Yang, Liulu Yang, Hongjie Ren, Wenhao Li, Yasser Mahmmod, Xiu-Xiang Zhang, Ziguo Yuan, Hao Yuan and Yan Zhang

Vaccines 2025, 13(8), 851; https://doi.org/10.3390/vaccines13080851 - 11 Aug 2025

Abstract

Background: Toxoplasma gondii (T. gondii) is a significant opportunistic zoonotic protozoan, presenting a substantial risk to human health and livestock. Consequently, the development of an effective vaccine against toxoplasmosis is imperative. This study focuses on the GRA12 protein as a [...] Read more.

Background: Toxoplasma gondii (T. gondii) is a significant opportunistic zoonotic protozoan, presenting a substantial risk to human health and livestock. Consequently, the development of an effective vaccine against toxoplasmosis is imperative. This study focuses on the GRA12 protein as a target for developing a recombinant protein vaccine, with its efficacy evaluated through immunization trials in cats. Methods: We expressed recombinant GRA12 protein in E. coli and immunized cats with the purified antigen. The cats were categorized into four groups: G1 (PBS control), G2 (ISA 201 adjuvant alone), G3 (rGRA12 vaccine), and G4 (rGRA12 combined with ISA 201 adjuvant). All cats underwent subcutaneous immunizations on days 0, 14, and 28. Subsequently, serum levels of IgG (including IgG1 and IgG2a subclasses) and cytokines (IFN-γ, IL-2, TNF-α, IL-4, IL-10) were measured by enzyme-linked immunosorbent assay (ELISA). Two weeks after the third immunization (42 DPI), each cat was intraperitoneally infected with 1 × 10⁶T. gondii RH tachyzoites. Oocyst shedding, survival duration, and T. gondii burden were monitored to assess vaccine-induced immunity. Results: The results indicate that immunization with recombinant rGRA12 protein significantly elevated IgG, IgG1, and IgG2a antibody levels in cats. G4 displayed elevated IgG levels post-immunization compared to G1 and G2, with an IgG1/IgG2a ratio > 1, indicating a mixed Th1/Th2 immune response. G4 also showed significantly increased IFN-γ, IL-2, TNF-α, and IL-4 levels compared to G1 (p < 0.05), while IL-10 remained unchanged. After T. gondii infection, total oocyst counts were 4.61 × 10⁶ (G1), 4.49 × 10⁶ (G2), 3.58 × 10⁶ (G3), and 2.59 × 10⁶ (G4), with G3/G4 showing 20.1–27.9% reduction relative to G1 (p < 0.05). Survival analysis revealed that groups G3 and G4 exhibited significantly longer median survival times (38 and 60 days, respectively; G4 with no mortality) compared to G1 and G2 (19 and 26 days, respectively). Additionally, parasite burdens in the brain, heart, lungs, liver, and spleen were significantly reduced in G3/G4 compared to G1/G2 (p < 0.01). Conclusions: In summary, the recombinant GRA12 vaccine significantly enhanced host survival and reduced parasite burden, demonstrating its potential as an effective toxoplasmosis vaccine candidate. These findings provide valuable data for future toxoplasmosis vaccine development. Full article

(This article belongs to the Special Issue The Development of Vaccine Against Parasite Infection)

► Show Figures

Figure 1

12 pages, 1043 KiB

Open AccessArticle

Impact of Vaccination and Prior Infection on SARS-CoV-2 Viral Load in Preschool Children During the Omicron Pandemic

by Mitsuyoshi Suzuki, Akifumi Tokita, Mariko Inaba, Yoshimi Tada, Kyoko Shuri, Asako Miura, Mitsuharu Fukazawa, Masashi Fujioka, Yuko Sakai-Tagawa, Seiya Yamayoshi, Kiyoko Iwatsuki-Horimoto, Yoshihiro Kawaoka and Masaaki Miyazawa

Vaccines 2025, 13(8), 850; https://doi.org/10.3390/vaccines13080850 - 11 Aug 2025

Abstract

Background: Preschool-aged children can have difficulty adhering to infection control measures and were affected during the Omicron wave of the coronavirus disease 2019 (COVID-19) pandemic. However, the impacts of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination on viral load [...] Read more.

Background: Preschool-aged children can have difficulty adhering to infection control measures and were affected during the Omicron wave of the coronavirus disease 2019 (COVID-19) pandemic. However, the impacts of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination on viral load in this age group remain poorly understood. This study aimed to investigate the relationship between previous SARS-CoV-2 infection, COVID-19 vaccination, and viral load or clinical severity in preschool-aged children infected during the Omicron variant epidemic in Japan. Methods: This prospective observational study investigated 107 children aged 1–75 months who were diagnosed with COVID-19 between May and September 2023. Rapid antigen (Ag) tests were performed on days 1 and 5 or 6, and results were visually graded into four categories (–, ±, 1+, or 2+). Ag results were validated against quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) cycle threshold (Ct) values. Clinical parameters, including vaccination status, previous infection, age, maximum body temperature, and fever duration, were analyzed using multivariate regression models. Results: Higher Ag loads (1+/2+) were more frequently observed in younger children who had not experienced prior infection or full vaccination. Prior infection and vaccination were independently linked to lower Ag loads and reduced maximum body temperature. Many unvaccinated and infection-naïve children continued to show elevated Ag levels on day 5 or 6, corresponding to Ct values suggestive of potential infectivity. Conclusions: Prior SARS-CoV-2 infection and vaccination were linked to lower viral loads and milder febrile responses among preschool-aged children. These findings enhance our understanding of infection dynamics in this age group and may inform future discussions on public health strategies in pediatric settings. Full article

(This article belongs to the Special Issue Host–Virus Interactions and Vaccine Development)

► Show Figures

Figure 1

22 pages, 977 KiB

Open AccessViewpoint

Fast-Tracking Vaccine Manufacturing: CEPI’s Rapid Response Framework for the 100 Days Mission

by June Kim, Ramin Sabet-Azad, Dimki Patel, Gene Malin, Syed Hassan Askary and Anna Särnefält

Vaccines 2025, 13(8), 849; https://doi.org/10.3390/vaccines13080849 - 11 Aug 2025

Abstract

CEPI (the Coalition for Epidemic Preparedness Innovation)’s CMC rapid response framework is developed to support accelerated vaccine development, manufacturing, and roll-out for various outbreak scenarios to achieve the 100 Days Mission. The framework outlines coordinated deliverables across five functional areas: manufacturing processes, formulation, [...] Read more.

CEPI (the Coalition for Epidemic Preparedness Innovation)’s CMC rapid response framework is developed to support accelerated vaccine development, manufacturing, and roll-out for various outbreak scenarios to achieve the 100 Days Mission. The framework outlines coordinated deliverables across five functional areas: manufacturing processes, formulation, analytics, supply chain, and facilities. It could serve as a tool to streamline CMC and the related activities for rapid vaccine development, identify areas for improvement and innovation, and assess preparedness for the outbreak response. The framework emphasizes the importance of thorough preparation during interpandemic periods as the foundation for the 100 Days Mission and for gaining the confidence of health authorities and the public in vaccines. Full article

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

► Show Figures

Figure 1

15 pages, 276 KiB

Open AccessArticle

Rapid Development of a Theory-Based Targeted Intervention and Communication Plan for HPV Vaccine Introduction in Kosovo Using the Behaviour Change Wheel Model

by Florie Miftari Basholli, Edita Haxhiu, Isme Humolli, Merita Berisha, Siff Malue Nielsen and Sahil Khan Warsi

Vaccines 2025, 13(8), 848; https://doi.org/10.3390/vaccines13080848 - 10 Aug 2025

Abstract

Background: Human papillomavirus (HPV) infection is the leading cause of cervical cancer, which presents a significant health burden in low- and middle-income settings such as Kosovo^†, where it is the second leading cause of death among women. HPV vaccines are [...] Read more.

Background: Human papillomavirus (HPV) infection is the leading cause of cervical cancer, which presents a significant health burden in low- and middle-income settings such as Kosovo^†, where it is the second leading cause of death among women. HPV vaccines are highly effective and integral to global cervical cancer elimination efforts. In 2024, Kosovo^† introduced the HPV vaccine into its immunisation schedule via a school-based program targeting sixth-grade girls. Rapid, theory-based insights supported development of a tailored communication and intervention plan ahead of the introduction. Methods: Over a two-week period, qualitative research was conducted with 102 participants, including healthcare professionals, parents, girls in the target age group, school staff, and community influencers. Data collection, analysis, and intervention development were carried out using the Behaviour Change Wheel (BCW) model, underpinned by the Capability, Opportunity, and Motivation for Behaviour change (COM-B) theoretical framework. Results: Trust in school-based immunisation and healthcare professionals emerged as key drivers, while a predominance of capability- and physical-opportunity-related barriers across target groups underscored the need for targeted communication and capacity-building efforts for all stakeholders. Using the BCW model, communication and intervention activities were developed for implementation by partners. Conclusions: Using rapid insight research grounded in the BCW model enabled the timely identification of behavioural drivers and barriers to HPV vaccine acceptance and supported development of a targeted intervention plan. The findings echoed global research on HPV vaccine introduction, highlighting context-specific needs and enablers and contributing to a successful rollout marked by high uptake within the first six months. Full article

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

Journal Description

Vaccines

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI