Vaccines

14 pages, 8244 KiB

Open AccessArticle

Innovative Approaches to Combat Duck Viral Hepatitis: Dual-Specific Anti-DHAV-1 and DHAV-3 Yolk Antibodies

by Siqi Lei, Yuanhe Yang, Chengchen Zhao, Anguo Liu and Pingli He

Vaccines 2025, 13(2), 154; https://doi.org/10.3390/vaccines13020154 - 2 Feb 2025

Background and Objectives: Duck viral hepatitis (DVH), a highly contagious and acutely fatal avian disease, is characterized by convulsions, acute death, liver swelling, and hemorrhage, leading to substantial losses in the duck industry. However, there is no efficient prevention and control method for [...] Read more.

Background and Objectives: Duck viral hepatitis (DVH), a highly contagious and acutely fatal avian disease, is characterized by convulsions, acute death, liver swelling, and hemorrhage, leading to substantial losses in the duck industry. However, there is no efficient prevention and control method for DHV infection. Duck hepatitis A virus (DHAV) is one of the primary pathogens responsible for DVH. Methods: In this study, we prepared a highly effective anti-DHAV IgY antibody by immunizing Hy-Line Brown laying hens at the peak of egg production. Results and Conclusions: The neutralization index of this antibody was found to be up to 38.90 (DHAV-1 QYD strain) and 141.25 (DHAV-3 GY strain) in vitro. The antibody also exhibited effective prophylactic effects in a model of hepatic inflammation following the viral challenge of ducklings, with a dose of 0.5 mL per duckling (containing 64 mg/mL of IgY) significantly reducing DHAV-related mortality by 66%, providing substantial protection against the infection. Furthermore, it effectively alleviated oxidative damage caused by DHAV in the ducklings. The results of this study indicate that IgY has the potential for treating DHAV infection; it also provides a new way for the treatment of poultry diseases with specific antibodies. Full article

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12 pages, 1593 KiB

Open AccessArticle

Assessing Torquetenovirus (TTV) as a Biomarker for Immune Responses to SARS-CoV-2 mRNA Vaccines in People Living with HIV and Healthy Individuals

by Claudia Minosse, Pietro Giorgio Spezia, Valentina Mazzotta, Giulia Matusali, Silvia Meschi, Francesca Colavita, Davide Mariotti, Stefania Notari, Alessandra Vergori, Daniele Focosi, Enrico Girardi, Andrea Antinori and Fabrizio Maggi

Vaccines 2025, 13(2), 153; https://doi.org/10.3390/vaccines13020153 - 1 Feb 2025

Abstract

Background: Torquetenovirus (TTV) viremia is increasingly recognized as a marker of immune competence. In the context of COVID-19, TTV viral load (VL) has been shown to predict anti-Spike antibody levels in severely immunocompromised patients. This study aimed to evaluate whether pre-vaccine TTV [...] Read more.

Background: Torquetenovirus (TTV) viremia is increasingly recognized as a marker of immune competence. In the context of COVID-19, TTV viral load (VL) has been shown to predict anti-Spike antibody levels in severely immunocompromised patients. This study aimed to evaluate whether pre-vaccine TTV VL could predict humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines in people living with HIV (PLWH) and healthy individuals (HP). Methods: TTV VL was measured via real-time PCR in serum samples collected before the second and third doses of mRNA vaccines in 93 PLWH and 48 HP (second dose) and 255 PLWH and 48 HP (third dose). Immune responses were assessed through anti-SARS-CoV-2 receptor-binding domain (RBD) IgG, neutralizing antibodies, and IFN-γ release. Statistical analyses included correlation studies between TTV VL and vaccine-induced immune responses. Results: TTV VL did not significantly correlate with anti-RBD IgG or neutralizing antibody levels in either cohort; highlighting its limited predictive value for humoral responses in relatively immunocompetent populations. However, a strong inverse correlation was observed between TTV VL and IFN-γ release after the third, but not the second, vaccine dose. These findings suggest that higher TTV VL, indicative of reduced immune competence, may impair T-cell-mediated immunity to vaccines. Conclusions: In virologically suppressed PLWH and HP, TTV VL is not a reliable predictor of humoral immune responses to COVID-19 vaccines. However, its inverse relationship with cellular responses warrants further investigation in more immunosuppressed populations. These results reinforce the continuum model of TTV VL as a biomarker, with predictive utility increasing alongside the degree of immunosuppression Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)

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13 pages, 529 KiB

Open AccessArticle

Vaccination Coverage and Attitudes in Children and Adults on Biologic Therapies: Cocooning Strategies, Undervaccination Factors and Predictors of Favorable Attitudes

by Charikleia Kariniotaki, George Bertsias, Emmanouil Galanakis and Chrysoula Perdikogianni

Vaccines 2025, 13(2), 152; https://doi.org/10.3390/vaccines13020152 - 1 Feb 2025

Abstract

Background: Infections pose a significant risk of morbidity and mortality to patients on biologics, with the vaccination of both patients and their close contacts serving as a key preventive measure. Despite its importance, there are limited data on the vaccination coverage for this [...] Read more.

Background: Infections pose a significant risk of morbidity and mortality to patients on biologics, with the vaccination of both patients and their close contacts serving as a key preventive measure. Despite its importance, there are limited data on the vaccination coverage for this group, and no studies have examined the vaccination status of patients’ close contacts. Objectives: To assess vaccination rates among patients on biologics and their household contacts, identifying reasons for inadequate vaccination and examining factors influencing vaccination status and attitudes is crucial. Methods: A cross-sectional study was conducted from September 2022 to February 2023 at the two hospitals in Heraklion, Crete, including adult and pediatric patients on biologics. Data were collected through medical records and interviews and analyzed using Microsoft Excel 2016 and MedCalc2006. Results: Among the 446 adults, vaccination rates were as follows: 83% for COVID-19, 73.8% for influenza, 64.5% for the pneumococcal conjugate vaccine, 29.6% for the pneumococcal polysaccharide vaccine, and 4% for Tdap. Among the 26 children included, those with basic immunization schedule coverage exceeded 96%, but rates for the vaccines usually administered at adolescence were lower (Tdap: 47.8%, HPV: 42.1%, MenACWY: 66.7%). COVID-19 vaccination was at 38.5%. Regarding the additional vaccines recommended due to treatment-induced immunosuppression, 69.2% of pediatric patients received the annual influenza vaccine, while only 19.2% received the pneumococcal polysaccharide vaccine. Household contacts demonstrated low vaccination rates (<59%), except for COVID-19 (81%). Female gender (p < 0.007) and older age (by 1 year, p < 0.001) were associated with favorable attitudes and higher coverage in adults, while in pediatric patients, no statistically significant associations were found. A lack of physician recommendation was the primary reported reason for not being vaccinated. Conclusions: Significant vaccination gaps exist among patients on biologics and their close contacts, largely due to inadequate physician recommendations. Raising awareness and strengthening healthcare provider roles are essential to improve coverage in this high-risk group. Full article

(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 2nd Edition)

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26 pages, 1081 KiB

Open AccessReview

Q Fever Vaccines: Unveiling the Historical Journey and Contemporary Innovations in Vaccine Development

by Magdalini Christodoulou and Dimitrios Papagiannis

Vaccines 2025, 13(2), 151; https://doi.org/10.3390/vaccines13020151 - 31 Jan 2025

Abstract

Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii that presents significant challenges for global public health control. Current prevention relies primarily on the whole-cell vaccine “Q-VAX”, which despite its effectiveness, faces important limitations including pre-screening requirements and [...] Read more.

Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii that presents significant challenges for global public health control. Current prevention relies primarily on the whole-cell vaccine “Q-VAX”, which despite its effectiveness, faces important limitations including pre-screening requirements and reactogenicity issues in previously sensitized individuals. This comprehensive review examines the complex interplay between pathogen characteristics, host immune responses, and vaccine development strategies. We analyze recent advances in understanding C. burnetii’s molecular pathogenesis and host–pathogen interactions that have informed vaccine design. The evolution of vaccine approaches is evaluated, from traditional whole-cell preparations to modern subunit, DNA, and multi-epitope designs. Particular attention is given to innovative technologies, including reverse vaccinology and immunoinformatics, that have enabled the identification of novel antigenic targets. Recent clinical data demonstrating the safety and immunogenicity of next-generation vaccine candidates are presented, alongside manufacturing and implementation considerations. While significant progress has been made in overcoming the limitations of first-generation vaccines, challenges remain in optimizing immunogenicity while ensuring safety across diverse populations. This review provides a critical analysis of current evidence and future directions in Q fever vaccine development, highlighting promising strategies for achieving more effective and broadly applicable vaccines. Full article

(This article belongs to the Special Issue Development of Vaccines against Bacterial Infections)

13 pages, 2269 KiB

Open AccessArticle

Characterization and Protective Efficacy of a Salmonella Typhimurium ATCC 14028 sptP Mutant as a Live Attenuated Vaccine Candidate

by Nanlong Zhou, Yonghui Ding, Ting He, Yuling Sun, Hongfang Chen, Meiling Huang and Tiansen Li

Vaccines 2025, 13(2), 150; https://doi.org/10.3390/vaccines13020150 - 31 Jan 2025

Abstract

Background: Salmonella Typhimurium poses a substantial health risk to both humans and animals. This study evaluated the potential of using the Salmonella Typhimurium ΔsptP mutant as a live-attenuated vaccine candidate by constructing it through homologous recombination and assessing its key biological properties, including growth [...] Read more.

Background: Salmonella Typhimurium poses a substantial health risk to both humans and animals. This study evaluated the potential of using the Salmonella Typhimurium ΔsptP mutant as a live-attenuated vaccine candidate by constructing it through homologous recombination and assessing its key biological properties, including growth characteristics, immunogenicity, and protective efficacy. Methods: We generated the ΔsptP mutant through targeted gene deletion, ensuring the preservation of the bacterial strain’s growth and stability. In vitro and in vivo assays were performed to compare the invasive capabilities between the mutant and the wild-type strains. Specifically, we examined the invasion into RAW264.7 murine macrophages and mice. Furthermore, the virulence of the mutant was evaluated by determining the median lethal dose (LD₅₀). To evaluate immunogenicity and protection, mice were immunized with 2 × 10⁴ CFUs of the ΔsptP mutant, followed by a booster immunization, and then challenged with a virulent strain. Results: The ΔsptP mutant exhibited no significant changes in growth characteristics or genetic stability compared to the wild-type strain. However, it demonstrated a significantly diminished capacity for invasion in both murine macrophages and mice. The LD₅₀ for the mutant was 39.92-fold higher than that of the wild-type, indicating a marked reduction in virulence. Mice immunized with the ΔsptP mutant and administered a booster immunization exhibited 87.5% protection against challenge with a virulent strain, as compared to the PBS control group. Moreover, the mutant induced IgG antibody levels comparable to those induced by the wild-type strain. Conclusions: The ΔsptP mutant of Salmonella Typhimurium exhibits markedly reduced virulence while retaining robust immunogenicity and protective efficacy. These findings suggest that the ΔsptP mutant is a promising candidate for a live-attenuated vaccine, potentially providing an effective strategy to prevent Salmonella Typhimurium infections. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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22 pages, 3077 KiB

Open AccessArticle

Design and Immune Profile of Multi-Epitope Synthetic Antigen Vaccine against SARS-CoV-2: An In Silico and In Vivo Approach

by Maria da Conceição Viana Invenção, Larissa Silva de Macêdo, Ingrid Andrêssa de Moura, Lucas Alexandre Barbosa de Oliveira Santos, Benigno Cristofer Flores Espinoza, Samara Sousa de Pinho, Lígia Rosa Sales Leal, Daffany Luana dos Santos, Bianca de França São Marcos, Carolina Elsztein, Georon Ferreira de Sousa, Guilherme Antonio de Souza-Silva, Bárbara Rafaela da Silva Barros, Leonardo Carvalho de Oliveira Cruz, Julliano Matheus de Lima Maux, Jacinto da Costa Silva Neto, Cristiane Moutinho Lagos de Melo, Anna Jéssica Duarte Silva, Marcus Vinicius de Aragão Batista and Antonio Carlos de Freitas

Vaccines 2025, 13(2), 149; https://doi.org/10.3390/vaccines13020149 - 31 Jan 2025

Abstract

Background: The rapid advancement of the pandemic caused by SARS-CoV-2 and its variants reinforced the importance of developing easy-to-edit vaccines with fast production, such as multi-epitope DNA vaccines. The present study aimed to construct a synthetic antigen multi-epitope SARS-CoV-2 to produce a DNA [...] Read more.

Background: The rapid advancement of the pandemic caused by SARS-CoV-2 and its variants reinforced the importance of developing easy-to-edit vaccines with fast production, such as multi-epitope DNA vaccines. The present study aimed to construct a synthetic antigen multi-epitope SARS-CoV-2 to produce a DNA vaccine. Methods: A database of previously predicted Spike and Nucleocapsid protein epitopes was created, and these epitopes were analyzed for immunogenicity, conservation, population coverage, and molecular docking. Results: A synthetic antigen with 15 epitopes considered immunogenic, conserved even in the face of variants and that were able to anchor themselves in the appropriate HLA site, together had more than 90% worldwide coverage. A multi-epitope construct was developed with the sequences of these peptides separated from each other by linkers, cloned into the pVAX1 vector. This construct was evaluated in vivo as a DNA vaccine and elicited T CD4+ and T CD8+ cell expansion in the blood and spleen. In hematological analyses, there was an increase in lymphocytes, monocytes, and neutrophils between the two doses. Furthermore, based on histopathological analysis, the vaccines did not cause any damage to the organs analyzed. Conclusions: The present study generated a multi-epitope synthetic vaccine antigen capable of generating antibody-mediated and cellular immune responses. Full article

(This article belongs to the Special Issue New Approaches to Vaccine Development and Delivery)

28 pages, 798 KiB

Open AccessReview

Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview

by Alex C. Boomgarden and Chitra Upadhyay

Vaccines 2025, 13(2), 148; https://doi.org/10.3390/vaccines13020148 - 31 Jan 2025

Abstract

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability [...] Read more.

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines and mRNA technology to induce broadly neutralizing antibodies, have shown promise. However, the efficacy of these vaccines has been modest, with the best results achieving approximately 30% effectiveness. Ongoing research emphasizes the necessity of a multifaceted strategy to overcome these obstacles and achieve a breakthrough in HIV-1 vaccine development. This review summarizes current approaches utilized to further understand HIV-1 biology and to create a global vaccine. We discuss the impact of these approaches on vaccine development for other diseases, including COVID-19, influenza, and Zika virus. Additionally, we highlight the specific limitations faced with each approach and present the methods researchers employ to overcome these challenges. These innovative techniques, which have demonstrated preclinical and clinical success, have advanced the field closer to the ultimate goal of developing a global HIV-1 vaccine. Leveraging these advancements will enable significant strides in combating HIV-1 and other infectious diseases, ultimately improving global health outcomes. Full article

(This article belongs to the Special Issue Advances in HIV Vaccine Development)

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20 pages, 1751 KiB

Open AccessArticle

COVID-19 Vaccination Uptake and Effectiveness for Hospitalized Cases Among Healthcare Workers in Tertiary Hospital

by María Eugenia Jiménez-Corona, Luis-Pablo Cruz-Hervert, María del Rocío Sánchez-Díaz, Gabriel Chavira-Trujillo, Aída Jiménez-Corona and María del Rosario Vázquez-Larios

Vaccines 2025, 13(2), 147; https://doi.org/10.3390/vaccines13020147 - 31 Jan 2025

Abstract

Background/Objectives: Healthcare workers (HCWs) faced elevated risks during the coronavirus disease 2019 (COVID-19) pandemic. Vaccination among HCWs was a key strategy to mitigate severe outcomes and maintain healthcare system functionality during the crisis. The aim of this study was to assess the [...] Read more.

Background/Objectives: Healthcare workers (HCWs) faced elevated risks during the coronavirus disease 2019 (COVID-19) pandemic. Vaccination among HCWs was a key strategy to mitigate severe outcomes and maintain healthcare system functionality during the crisis. The aim of this study was to assess the distribution, severity, and clinical factors associated with COVID-19 among HCWs in a tertiary hospital across eight pandemic waves and evaluate the effectiveness of vaccination in reducing severe outcomes. Methods: A cross-sectional study analyzed data from HCWs at a high-specialty hospital in Mexico City from March 2020 to February 2024. Sociodemographic, clinical, and vaccination data were collected and analyzed via bivariate and multivariable logistic regression to identify the factors associated with infection and severity. Results: A total of 7049 cases were analyzed, and 2838 (40.26%) were confirmed COVID-19 cases. Severe outcomes, including hospitalizations and deaths, were most common during the early waves, with 83.3% of severe cases occurring among unvaccinated individuals. Vaccination significantly reduced infection risk, with individuals receiving two or more doses showing a lower likelihood of infection (OR 0.67; 95% CI 0.51–0.89; p = 0.005). Older age; comorbidities such as hypertension and obesity; and symptoms such as fever were associated with increased severity. Compared with earlier coverage, enhanced vaccination coverage significantly lowered the hospitalization risk during the later waves (OR 11.11; 95% CI 1.2–110.2; p = 0.040). Conclusions: Vaccination effectively reduced severe COVID-19 outcomes among HCWs, demonstrating its critical role in mitigating the disease burden despite the high risk of exposure. Strategies such as targeted vaccination campaigns and continuous surveillance are essential to protect HCWs and ensure healthcare system resilience. Full article

(This article belongs to the Special Issue Human Immune Responses to Infection and Vaccination)

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17 pages, 3837 KiB

Open AccessArticle

Dynamic Immune Response Landscapes of Avian Peripheral Blood Post-Vaccination Against Infectious Bronchitis Virus Infection

by Xuefeng Li, Yumeng Liang, Yu Zhang, Zheyi Liu, Lu Cui, Miaomiao Xi, Shufeng Feng, Xiaoxiao Liu, Yongxin Zhu, Shengwang Liu and Hai Li

Vaccines 2025, 13(2), 146; https://doi.org/10.3390/vaccines13020146 - 30 Jan 2025

Abstract

Background/Objectives: Despite decades of extensive vaccinations against avian infectious bronchitis virus (IBV) infection, outbreaks caused by constantly emerging variants due to genome recombination between different viral strains, including vaccine strains, occur annually worldwide. The development of novel vaccines with favorable safety and [...] Read more.

Background/Objectives: Despite decades of extensive vaccinations against avian infectious bronchitis virus (IBV) infection, outbreaks caused by constantly emerging variants due to genome recombination between different viral strains, including vaccine strains, occur annually worldwide. The development of novel vaccines with favorable safety and effectiveness is required but is hindered by a limited understanding of vaccination against IBV. Methods: Here, we performed a comprehensive analysis of the in vivo dynamics of peripheral blood mononuclear cells (PBMCs) in specific pathogen-free chickens inoculated with the widely used live attenuated IBV vaccine strain H120 at single-cell level, using high-throughput single-cell transcriptome sequencing (scRNA-seq). Results: High-quality sequencing dataset for four scRNA-seq data containing the transcriptomes of 29,846 individual chicken PBMCs were obtained, defining 22 populations and 7 cell types based on distinct molecular signatures and known markers. Further integrative analysis constructed the time series dynamic cell transition and immune response landscapes within the two weeks post-prime vaccination against IBV. Enhanced crosstalk between antigen-presenting cells and T lymphocytes was revealed as early as four days post-vaccination. The specific immune cell populations and their comprehensive cellular and molecular networks involved in the initiation phase of antiviral adaptive immune responses were elucidated in details. Conclusions: Our study provides a comprehensive view of the dynamic initiation of immune responses in chickens against IBV infection at the cellular and molecular levels, which provides theoretical support and potential solutions for the future rational design of safe and effective vaccines, the augmentation of the efficacy of current vaccines, and the optimization of immune programs. Full article

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17 pages, 1048 KiB

Open AccessReview

Dengue Vaccination: A Practical Guide for Clinicians

by Kay Choong See

Vaccines 2025, 13(2), 145; https://doi.org/10.3390/vaccines13020145 - 30 Jan 2025

Abstract

Dengue is a growing global public health challenge, with rising incidence and case fatality rates fueled by urbanization and climate change. The substantial mortality, morbidity, and economic burden associated with the disease underscore the need for effective prevention strategies, including vector control, personal [...] Read more.

Dengue is a growing global public health challenge, with rising incidence and case fatality rates fueled by urbanization and climate change. The substantial mortality, morbidity, and economic burden associated with the disease underscore the need for effective prevention strategies, including vector control, personal protective measures, and vaccination. This narrative review provides a practical guide for clinicians to ensure the appropriate administration of dengue vaccines to at-risk groups, such as individuals in endemic regions and travelers to these areas. Live-attenuated tetravalent dengue vaccines, including Dengvaxia^®, Qdenga^®, and Butantan-DV, have demonstrated efficacy in clinical trials but require careful use due to the risk of antibody-dependent enhancement (ADE). To mitigate this risk, guidelines recommend vaccination primarily for individuals with prior confirmed dengue infection, emphasizing the importance of accessible and affordable point-of-care rapid testing. Co-administration of dengue vaccines with other live-attenuated or inactivated vaccines has been shown to be safe and immunogenic, broadening their potential application. However, live-attenuated vaccines are contraindicated for immunocompromised individuals and pregnant women. Enhancing clinician awareness, expanding diagnostic capabilities, and prioritizing high-risk populations are critical steps to optimize vaccination strategies. Combined with robust prevention programs, these efforts are essential to reducing the global burden of dengue and mitigating its impact. Full article

(This article belongs to the Special Issue Emerging Insights: Vaccine Efficacy and Clinical Dynamics in the Context of Multiple Pathogen Exposures)

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27 pages, 2342 KiB

Open AccessReview

Manufacturing and Financial Evaluation of Peptide-Based Neoantigen Cancer Vaccines for Triple-Negative Breast Cancer in the United Kingdom: Opportunities and Challenges

by Adriana Novakova, Stephen A. Morris, Ludovica Vaiarelli and Stefanie Frank

Vaccines 2025, 13(2), 144; https://doi.org/10.3390/vaccines13020144 - 29 Jan 2025

Abstract

This review evaluates the financial burden of current treatments for triple-negative breast cancer (TNBC) and projects potential financial scenarios to assess the feasibility of introducing a peptide-based neoantigen cancer vaccine (NCV) targeting the disease, using the UK as a healthcare system model. TNBC, [...] Read more.

This review evaluates the financial burden of current treatments for triple-negative breast cancer (TNBC) and projects potential financial scenarios to assess the feasibility of introducing a peptide-based neoantigen cancer vaccine (NCV) targeting the disease, using the UK as a healthcare system model. TNBC, the most aggressive breast cancer subtype, is associated with poor prognosis, worsened by the lack of personalised treatment options. Neoantigen cancer vaccine therapies present a personalised alternative with the potential to enhance T-cell responses independently of genetic factors, unlike approved immunotherapies for TNBC. Through a systematic literature review, the underlying science and manufacturing processes of NCVs are explored, the direct medical costs of existing TNBC treatments are enumerated, and two contrasting pricing scenarios for NCV clinical adoption are evaluated. The findings indicate that limited immunogenicity is the main scientific barrier to NCV clinical advancement, alongside production inefficiencies. Financial analysis shows that the UK spends approximately GBP 230 million annually on TNBC treatments, ranging from GBP 2200 to GBP 54,000 per patient. A best-case pricing model involving government-sponsored NCV therapy appears financially viable, while a worst-case, privately funded model exceeds the National Institute for Health and Care Excellence (NICE) cost thresholds. This study concludes that while NCVs show potential clinical benefits for TNBC, uncertainties about their standalone efficacy make their widespread adoption in the UK unlikely without further clinical research. Full article

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

17 pages, 3285 KiB

Open AccessArticle

Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort

by Gerald Kevin Oluka, Jackson Sembera, Joseph Ssebwana Katende, Violet Ankunda, Laban Kato, Ashwini Kurshan, Carl Graham, Jeffrey Seow, Katie J. Doores, Michael H. Malim, Julie A. Fox, Pontiano Kaleebu and Jennifer Serwanga

Vaccines 2025, 13(2), 143; https://doi.org/10.3390/vaccines13020143 - 29 Jan 2025

Abstract

Background: This study assessed the long-term dynamics of neutralizing antibodies in a Ugandan cohort primarily exposed to the A.23.1 SARS-CoV-2 variant, examining how this shaped immune breadth and potency against diverse strains following infection and prototype-based vaccination. Methods: We conducted a 427-day retrospective [...] Read more.

Background: This study assessed the long-term dynamics of neutralizing antibodies in a Ugandan cohort primarily exposed to the A.23.1 SARS-CoV-2 variant, examining how this shaped immune breadth and potency against diverse strains following infection and prototype-based vaccination. Methods: We conducted a 427-day retrospective analysis of 41 participants across multiple SARS-CoV-2 waves, assessing binding and neutralizing antibody responses using in-house ELISA and pseudotyped virus neutralization assays. We quantified immune responses to key SARS-CoV-2 variants, A.23.1, D614G, Delta, and BA.4, capturing evolving immunity across the pandemic. Results: Neutralizing antibody titers against A.23.1 remained significantly higher than those against D614G, Delta, and BA.4, highlighting the solid immune memory following A.23.1 infection. Consistently lower titers were observed for BA.4 across all time points, aligning with its strong immune-evasion capability. Correlations between neutralizing titers and spike-directed IgG (S-IgG) concentrations were significantly stronger for A.23.1 than for D614G, with no correlation for BA.4. ChAdOx1-S vaccination substantially elevated the neutralizing titers across all variants, most notably BA.4, highlighting the essential role of vaccination in boosting immunity, even in individuals with initially low titers. Conclusions: Initial exposure to the A.23.1 variant triggered potent immune responses, shaping neutralizing antibody dynamics during subsequent exposures. These findings highlight the importance of accounting for early viral exposures in vaccine development and public health planning. The distinctly lower immune response to BA.4 highlights the need for continuous antigenic monitoring and timely vaccine updates for protection against emerging variants. Vaccination remains essential for reinforcing and sustaining immunity against evolving variants. Full article

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

23 pages, 788 KiB

Open AccessArticle

Resilience in the Vaccine Supply Chain: Learning from the COVID-19 Pandemic

by Megan Hay, Anika Teichert, Sarah Kilz and Agnes Vosen

Vaccines 2025, 13(2), 142; https://doi.org/10.3390/vaccines13020142 - 29 Jan 2025

Abstract

Background: The COVID-19 pandemic revealed vaccine supply chain (VSC) weaknesses and enabled post-pandemic analysis highlighting the growing importance of supply chain resilience. This study analyzes weaknesses and potentials for VSC resilience from an industry perspective. Insights from this study are aimed at supporting [...] Read more.

Background: The COVID-19 pandemic revealed vaccine supply chain (VSC) weaknesses and enabled post-pandemic analysis highlighting the growing importance of supply chain resilience. This study analyzes weaknesses and potentials for VSC resilience from an industry perspective. Insights from this study are aimed at supporting helping managers and policy-makers build a more resilient vaccine supply. Methods: A qualitative semi-structured interview study was conducted with 12 industry experts along the VSC. The interviews were assessed concerning the learnings from the pandemic in a two-step content analysis. Codes were assigned to key VSC concepts and variables and then linked to political, economic, social, technological, legal, and environmental (PESTLE) dimensions. The complex multi-stakeholder supply chain was visualized in a system overview, highlighting main actors, roles, constraints, and resilience. Results: The analysis resulted in 60 codes, categorized into the six PESTLE dimensions and three additional (sub)groups (mRNA, Supply chain resilience, and Solutions). The largest dimension was Economic, with 39 codes, including the Supply chain resilience subgroup. Twelve stakeholder groups were identified, with purchasers, manufacturers, suppliers, developers, and regulatory agencies being the most significant in emergency vaccine manufacturing situations. Conclusions: The system overview demonstrated the VSC as a complex network of actors with unaligned goals rather than a linear supply chain. This study shows that the VSC is characterized by uncertainty due to external factors, like the unpredictability of new emergencies, and internal factors like vaccine demand. The lack of transparency between industry stakeholders exacerbates VSC disruption. We conclude that infrastructures and management practices that enable increased transparency and collaboration between stakeholders hold the greatest potential for strengthening the VSC’s resilience to future pandemics. Full article

(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)

3 pages, 169 KiB

Open AccessComment

Comment on Kerro Dego et al. Evaluation of Streptococcus uberis Surface Proteins as Vaccine Antigens to Control S. uberis Mastitis in Dairy Cows. Vaccines 2021, 9, 868

by Rosa Collado, Carlos Montbrau, David Sabaté and Antoni Prenafeta

Vaccines 2025, 13(2), 141; https://doi.org/10.3390/vaccines13020141 - 29 Jan 2025

Abstract

A recent publication by Kerro Dego et al [...] Full article

(This article belongs to the Section Veterinary Vaccines)

20 pages, 1721 KiB

Open AccessArticle

Cross-Reactive Fc-Mediated Antibody Responses to Influenza HA Stem Region in Human Sera Following Seasonal Vaccination

by Ayae Nishiyama, Takuto Nogimori, Yuji Masuta, Tomoka Matsuura, Tetsuo Kase, Kyoko Kondo, Satoko Ohfuji, Yu Nakagama, Natsuko Kaku, Sachie Nakagama, Yuko Nitahara, Yoshimasa Takahashi, Hiroshi Kakeya, Yasutoshi Kido, Wakaba Fukushima and Takuya Yamamoto

Vaccines 2025, 13(2), 140; https://doi.org/10.3390/vaccines13020140 - 28 Jan 2025

Abstract

Background: Current influenza A vaccines primarily induce neutralizing antibodies targeting the variable hemagglutinin (HA) head domain, limiting their effectiveness against diverse or emerging influenza A virus (IAV) subtypes. The conserved HA stem domain, particularly the long α-helix (LAH) epitope, is a focus of [...] Read more.

Background: Current influenza A vaccines primarily induce neutralizing antibodies targeting the variable hemagglutinin (HA) head domain, limiting their effectiveness against diverse or emerging influenza A virus (IAV) subtypes. The conserved HA stem domain, particularly the long α-helix (LAH) epitope, is a focus of universal vaccine research due to its cross-protective potential. Additionally, Fc-mediated functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are recognized as important protective immune mechanisms. This study evaluated IgG responses to the HA head, stem, and LAH regions and assessed cross-reactive potential through neutralization, ADCC, and ADCP assays. Methods: IgG responses to the HA head, stem, and LAH regions were measured in vaccinated individuals. Functional assays were conducted for neutralization, ADCC, and ADCP to evaluate the association between antibody levels and immune function. Results: The results showed that HA head-specific IgG increased significantly after vaccination in 50 individuals, whereas stem-specific IgG increased by 72% and LAH-specific IgG by 12–14%. Among the induced antibody subclasses, IgG1 was predominantly increased. Neutralization titers were detected in viruses of the same strain as the vaccine strain, but not in classical or pandemic strains (H5N1, H7N9). HA stem-specific IgG1 antibody titers showed a significant correlation with ADCC/ADCP activity breadth, but no correlation was observed with neutralization breadth. Conclusion: These findings suggest that although current influenza vaccines can induce HA stem-targeted cross-reactive antibodies, their quantity may be insufficient for broad cross-protection, underscoring the need for improved vaccine strategies. Full article

(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)

17 pages, 3847 KiB

Open AccessArticle

Evaluation of Zein Nanoparticles as Delivery Agents of SARS-CoV-2 Antigens

by Verónica Araceli Márquez-Escobar, María José Alonso-Cerda, Sergio Rosales-Mendoza and María de Lourdes Betancourt-Mendiola

Vaccines 2025, 13(2), 139; https://doi.org/10.3390/vaccines13020139 - 28 Jan 2025

Abstract

Background/Objectives: Nanovaccines have significant potential to enhance immunization strategies by improving efficacy, safety, and cost-effectiveness. In particular, organic nanoparticles hold promise for the generation of low-cost nanovaccines obtained by environmentally friendly methods. In this study, the feasibility of using zein nanoparticles (NPs) as [...] Read more.

Background/Objectives: Nanovaccines have significant potential to enhance immunization strategies by improving efficacy, safety, and cost-effectiveness. In particular, organic nanoparticles hold promise for the generation of low-cost nanovaccines obtained by environmentally friendly methods. In this study, the feasibility of using zein nanoparticles (NPs) as carriers for an antigenic peptide (p30) and the receptor binding domain (RBD) from SARS-CoV-2 spike protein was explored. Methods: A synthesis method for zein NPs was established by combining previously reported techniques, and the resulting NPs were characterized in terms of morphology, particle size, polydispersity index (PDI), surface charge, and colloidal stability using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Tween 20 was employed as a surfactant to enhance particle stability and prevent aggregation. Results: The zein NPs were deemed safe based on an in vitro cytotoxicity assay using Vero cells. Immunogenicity assessments demonstrated that zein NPs:p30 and zein NPs:RBD induced IgG responses in test mice, whose magnitude was comparable to those achieved with alum as an adjuvant. Conclusions: These findings support the use of zein NPs as promising vaccine delivery vehicles with adjuvant effects due to their ease and environmentally friendly synthesis, high stability, and low cost. Full article

(This article belongs to the Special Issue Nanoparticle-Based Delivery Systems for Vaccines)

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10 pages, 364 KiB

Open AccessArticle

Vaccination Coverages Among Splenectomized Patients: A Retrospective Study from an Italian Southern Province

by Giuseppe Di Martino, Riccardo Mazzocca, Tania Masci, Lisa Berghella, Jacopo Del Papa, Francesco D’Aloisio, Mario Messinese, Fabrizio Cedrone, Patrizia Marani Toro and Graziella Soldato

Vaccines 2025, 13(2), 138; https://doi.org/10.3390/vaccines13020138 - 28 Jan 2025

Abstract

Background: Splenectomized patients have a higher risk compared to the general population of developing post-splenectomy infection, particularly by capsulated bacteria. Splenectomized patients need to be vaccinated against pneumococcal diseases, meningococcal disease, and heamophilus influenzae (Hib) in order to avoid invasive bacterial diseases. This [...] Read more.

Background: Splenectomized patients have a higher risk compared to the general population of developing post-splenectomy infection, particularly by capsulated bacteria. Splenectomized patients need to be vaccinated against pneumococcal diseases, meningococcal disease, and heamophilus influenzae (Hib) in order to avoid invasive bacterial diseases. This study evaluated vaccination coverages among splenectomized patients in a Southern Italian province. Methods: A retrospective study was conducted evaluating all splenectomized patients from the Pescara province from 2015 to 2023. Vaccination coverages were calculated before and after splenectomy for the following vaccines: pneumococcal disease, meningococcal disease, Hib, and COVID-19. Results: A total of 97 patients were considered during the study period. Vaccination coverages were low before surgery, but they increased after splenectomy. Higher coverages were found against pneumococcal diseases (77.3%), meninigococcal disease (58.8%), and COVID-19 (91.8%). Conclusions: Vaccination coverages among splenectomized patients in the Pescara province are not satisfying. It is imperative to implement educational measures for patients and physicians to increase vaccination coverages. Full article

(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)

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14 pages, 3270 KiB

Open AccessArticle

Effective Immune Protection of Mice from Murine Cytomegalovirus Infection by Oral Salmonella-Based Vaccine Expressing Viral M78 Antigen

by Yujun Liu, Hao Gong, Jiaming Zhu and Fenyong Liu

Vaccines 2025, 13(2), 137; https://doi.org/10.3390/vaccines13020137 - 28 Jan 2025

Abstract

Background: Human cytomegalovirus (CMV) is the most common cause of viral congenital infections worldwide. The development of effective vaccines against human CMV infection and disease is a high priority. Attenuated Salmonella are attractive oral vaccine vectors against human diseases because they can [...] Read more.

Background: Human cytomegalovirus (CMV) is the most common cause of viral congenital infections worldwide. The development of effective vaccines against human CMV infection and disease is a high priority. Attenuated Salmonella are attractive oral vaccine vectors against human diseases because they can be administrated orally. Methods: In this study, an attenuated Salmonella strain was generated as an oral vaccine vector for the delivery and expression of the M78 protein of murine cytomegalovirus (MCMV). Using the MCMV infection of mice as the CMV infection model, we characterized the immune responses and protection induced by the constructed Salmonella-based vaccine. Results: The generated Salmonella-based vaccine, v-M78, which contained an M78 expression plasmid construct, carried out gene transfer efficiently for M78 expression and showed little pathogenicity and virulence in mice. In orally vaccinated mice, v-M78 induced anti-MCMV serum IgG and mucosal IgA responses and also elicited anti-MCMV T cell responses. Furthermore, mice immunized with v-M78 were protected from intraperitoneal and intranasal challenges with MCMV. The v-M78 vaccination reduced the titers of the challenged viruses in spleens, livers, lungs, and salivary glands. Conclusions: These results provide the first direct evidence that a Salmonella-based vaccine expressing M78 elicits strong humoral and cellular immune responses and induces immune protection against MCMV infection. Furthermore, our study demonstrates the potential of using Salmonella-based oral vaccines against CMV infection. Full article

(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)

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15 pages, 5046 KiB

Open AccessArticle

Immunoprotection Provided by Salivary and Intestinal Protein-Based Antigens Against the Ixodid Tick Amblyomma sculptum

by Ulisses A. Natividade, Jessica F. Abreu, Izabela C. T. Ribeiro, Adalberto A. Pereira Filho, Augusto V. Silva, Helen S. Ribeiro, Rodolfo C. Giunchetti, Mauricio R. V. Sant’Anna, Nelder F. Gontijo, Marcos H. Pereira and Ricardo N. Araujo

Vaccines 2025, 13(2), 136; https://doi.org/10.3390/vaccines13020136 - 28 Jan 2025

Abstract

Background/Objectives: Amblyomma sculptum is among the most dangerous ticks in South America, as it is the species most associated with humans and is the main vector of Rickettsia rickettsii. In the face of the problems related to tick control based on [...] Read more.

Background/Objectives: Amblyomma sculptum is among the most dangerous ticks in South America, as it is the species most associated with humans and is the main vector of Rickettsia rickettsii. In the face of the problems related to tick control based on chemical acaricides, vaccines emerge as a promising method. In previous works, three salivary recombinant proteins (rAs8.9kDa, rAsKunitz, and rAsBasicTail) and one protein based on intestinal immunogenic regions (rAsChimera) were described with 59 to 92% vaccine efficacy against A. sculptum females. Here, we evaluate novel vaccine formulations containing binary or multiple combinations of the antigens rAs8.9kDa, rAsKunitz, rAsBasicTail, and rAsChimera against the three instars of the tick. Methods: A control group of mice was immunized with adjuvant alone (aluminum hydroxide gel) and compared to five groups immunized with formulations containing two, three, or four of the antigens. Results: The formulations were safe, with no significant alterations to host behavior and hematological or biochemical parameters. Immunizations induced a significant increase in the CD19⁺ B lymphocyte percentage in all groups, but no difference was seen for CD8⁺ and CD4⁺ T lymphocytes or CD14⁺ monocytes. The best protection was observed for the formulations containing two antigens, which reached above 98% efficacy, while the groups containing three or four antigens presented 92.7 and 94.4% efficacy, respectively. Conclusions: All antigen combinations were promising as vaccine formulations against A. sculptum. The formulation containing rAs8.9kDa and rAsChimera showed the best efficacy and should be focused on in further experiments. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)

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