Vaccines

18 pages, 4140 KiB

Open AccessArticle

Immune Responses Induced by Recombinant Membrane Proteins of Mycoplasma agalactiae in Goats

by Beatriz Almeida Sampaio, Maysa Santos Barbosa, Matheus Gonçalves de Oliveira, Manoel Neres Santos Júnior, Bruna Carolina de Brito Guimarães, Emilly Stefane Souza Andres, Ágatha Morgana Bertoti da Silva, Camila Pacheco Gomes, Rafaela de Souza Bittencourt, Thiago Macêdo Lopes Correia, Lucas Santana Coelho da Silva, Jurandir Ferreira da Cruz, Rohini Chopra-Dewasthaly, Guilherme Barreto Campos, Jorge Timenetsky, Bruno Lopes Bastos and Lucas Miranda Marques

Vaccines 2025, 13(7), 746; https://doi.org/10.3390/vaccines13070746 - 11 Jul 2025

Abstract

Background/Objectives: Contagious agalactia (CA) is a disease typically caused by Mycoplasma agalactiae, affecting small ruminants worldwide and being endemic in certain countries. CA causes severe economic losses due to mastitis, agalactia, and arthritis. As an alternative to existing immunoprophylactic measures, this study [...] Read more.

Background/Objectives: Contagious agalactia (CA) is a disease typically caused by Mycoplasma agalactiae, affecting small ruminants worldwide and being endemic in certain countries. CA causes severe economic losses due to mastitis, agalactia, and arthritis. As an alternative to existing immunoprophylactic measures, this study aimed to develop a recombinant subunit vaccine against M. agalactiae and evaluate its specific immune response in goats. Methods: Goats were divided into three groups: group 1 received recombinant proteins (P40 and MAG_1560), group 2 received formalin-inactivated M. agalactiae, and group 3 received Tris-buffered saline (negative control). All solutions were emulsified in Freund’s adjuvant. Animals were monitored for 181 days. IgG antibody production was assessed by ELISA, and peripheral blood mononuclear cells (PBMCs) were analyzed by real-time PCR for the expression of IL-1β, IFN-γ, IL-12, and MHC class II genes. Results: M. agalactiae-specific antibody response was observed for six months in the sera of animals from group 1. Analysis of cytokine gene expression revealed increased IL-1β mRNA levels over time in both experimental groups. In group 1, IFN-γ mRNA levels increased with P40 stimulation and decreased with MAG_1560. IL-12 mRNA expression decreased over time in group 1 with P40 stimulation, whereas group 2 showed increased IL-12 expression for both proteins. MHC-II expression was stimulated in both groups. Conclusions: The recombinant proteins induced antibody production and cytokine expression, demonstrating immunogenic potential and supporting their promise as vaccine candidates capable of eliciting both humoral and cellular immune responses against M. agalactiae. Full article

(This article belongs to the Section Veterinary Vaccines)

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18 pages, 2138 KiB

Open AccessArticle

Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza

by Hongzhe Lin, Yuxuan Jiang, Yan Li, Yiwei Zhong, Mingyue Chen, Weiyu Jiang, Rong Xiang, Najing Cao, Lei Sun, Xuanyi Wang, Lu Lu, Qiao Wang, Guangyue Han, Duan Ma and Bin Wang

Vaccines 2025, 13(7), 745; https://doi.org/10.3390/vaccines13070745 - 10 Jul 2025

Abstract

Background: Influenza remains a persistent public health challenge due to antigenic drift and shift, necessitating vaccines capable of eliciting broad and durable immunity. Hemagglutinin (HA) antigen serves as the critical target for eliciting protective immune responses against influenza. DNA vaccines offer distinct [...] Read more.

Background: Influenza remains a persistent public health challenge due to antigenic drift and shift, necessitating vaccines capable of eliciting broad and durable immunity. Hemagglutinin (HA) antigen serves as the critical target for eliciting protective immune responses against influenza. DNA vaccines offer distinct advantages over conventional platforms, including accelerated development and induction of both humoral and cellular immune responses. Methods: To optimize HA antigen presentation, we designed and systematically compared the immunogenicity and protective efficacy of HA antigen display strategies—bacteriophage T4 fibritin (HA-Foldon) and ferritin-based virus-like particles (HA-Ferritin)—versus monomeric HA DNA vaccines against seasonal influenza viruses. Results: HA-Ferritin showed superior structural stability. All vaccines induced similar HA-specific antibody levels, but HA-Ferritin elicited higher neutralizing antibodies and stronger T cell responses. Upon challenge, HA-Ferritin and HA-Foldon protected mice from weight loss and reduced lung virus loads by 3.27 and 0.76 times, respectively. Monomeric HA provided limited protection, with only 40% survival and minimal viral or pathological reduction. Conclusions: The HA-Ferritin DNA vaccine demonstrated enhanced immunogenicity and protection, supporting structured antigen display as a promising strategy for influenza DNA vaccine development. Full article

(This article belongs to the Special Issue Advances in DNA Vaccine Research)

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16 pages, 2024 KiB

Open AccessArticle

Recovering Immunogenic Orthohantavirus puumalaense N Protein from Pellets of Recombinant Escherichia coli

by Natalya Andreeva, Ekaterina Martynova, Polina Elboeva, Milana Mansurova, Ilnur Salafutdinov, Aleksandr Aimaletdinov, Rafil Khairullin, Diksha Sharma, Manoj Baranwal, Sara Chandy, Dilbar Dalimova, Alisher Abdullaev, Mirakbar Yakubov, Albert Rizvanov, Svetlana Khaiboullina, Yuriy Davidyuk and Emmanuel Kabwe

Vaccines 2025, 13(7), 744; https://doi.org/10.3390/vaccines13070744 - 10 Jul 2025

Abstract

(1) Background: Hemorrhagic fever with renal syndrome (HFRS) remains a prevalent zoonosis in Eurasia. Orthohantavirus puumalaense (PUUV), carried by bank voles (Myodes glareolus), is the principal zoonotic pathogen of HFRS in this region. Despite ongoing efforts to develop effective drugs and [...] Read more.

(1) Background: Hemorrhagic fever with renal syndrome (HFRS) remains a prevalent zoonosis in Eurasia. Orthohantavirus puumalaense (PUUV), carried by bank voles (Myodes glareolus), is the principal zoonotic pathogen of HFRS in this region. Despite ongoing efforts to develop effective drugs and vaccines against PUUV, this challenge remains. (2) Aim: In this study, we aimed to express a large quantity of the PUUV recombinant N (rN) protein using E. coli. We also sought to develop a protocol for extracting the rN protein from pellets, solubilizing, and refolding it to restore its native form. This protocol is crucial for producing a large quantity of rN protein to develop vaccines and diagnostic tools for HFRS. (3) Methods; PUUV S segment open reading frame (ORF) coding for N protein was synthesized and cloned into the plasmid vector pET-28 (A+). The ORF was transformed, expressed and induced in BL21(DE3) pLysS E. coli strain. Subsequently, rN protein was purified using immobilized metal affinity and ion chromatography. Immune reactivity of rN protein was tested by employing in house and commercial VektoHanta-IgG kit ELISA methods (both in vitro and in vivo). (4) Results: The best conditions for scaling up the expression of the PUUV rN protein were an incubation temperature of 20 °C during a 20 h incubation period, followed by induction with 0.5 mM IPTG. The most significant protein yield was achieved when the pellets were incubated in denaturing buffer with 8M urea. The highest yield of refolded proteins was attained using non-denaturing buffer (50 mM Tris-HCl) supplemented with arginine. A final 50 μL of PUUV rN protein solution with a concentration of 7 mg/mL was recovered from 1 L of culture. The rN protein elicited an antibody response in vivo and reacted with serum taken from patients with HFRS by ELISA in vitro. (5) Conclusion: Therefore, the orthohantavirus N protein’s ability to elicit immune response in vivo suggests that it can be used to develop vaccines against PUUV after conducting in vitro and in vivo studies to ascertain neutralising antibodies. Full article

(This article belongs to the Special Issue Protein- and Subunit-Based Vaccines)

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21 pages, 3801 KiB

Open AccessArticle

Immunogenicity, Efficacy and Twelve-Month Storage Stability Studies of a Lyophilized Rabies mRNA Vaccine

by Chen Chen, Dandan Ling, Kai Ji, Liang Tang, Xiaojing Zhang, Xishan Lu, Xuemei Leng, Changyao Tan, Hongchao Wu, Wenqiang Pang, Quanren He, Jerry Zhang, Peng Gao, Xiaotao Wang, Linhui Wang and Bo Ying

Vaccines 2025, 13(7), 743; https://doi.org/10.3390/vaccines13070743 - 10 Jul 2025

Abstract

Background: Many new mRNA-based vaccine candidates in liquid mRNA-LNP formulations are under development; however, their stability limitations necessitate frozen storage, posing a significant challenge for long-term storage and transportation. Methods: In this study, an mRNA-LNP rabies vaccine, ABO1005, was prepared, freeze-dried and stored [...] Read more.

Background: Many new mRNA-based vaccine candidates in liquid mRNA-LNP formulations are under development; however, their stability limitations necessitate frozen storage, posing a significant challenge for long-term storage and transportation. Methods: In this study, an mRNA-LNP rabies vaccine, ABO1005, was prepared, freeze-dried and stored at 2–8 °C for 12-month storage stability evaluation. The immunogenicity, vaccine potency (the NIH method), and protective efficacy of ABO1005 were assessed in mice or dogs and compared to a commercialized inactivated vaccine. Results: Research conducted in mice indicated that the lyophilized vaccine exhibited comparable immunogenicity to its liquid form counterpart. Furthermore, the vaccine candidate elicited a robust humoral response lasting at least 175 days, and the specific antibody titers were not affected by the pre-administration of hyperimmune serum. In comparison to the commercialized inactivated vaccine (HDCV or PVRV), ABO1005 elicited significantly higher levels of humoral and cellular immunity. Vaccine potency testing (NIH) revealed that the potency of ABO1005 at 15 μg/dose was 8.85 IU/dose, which is substantially higher than the standard required for the lot release of rabies vaccines for current human use. In a post-exposure prophylaxis (PEP) study in Beagle dogs, the lyophilized vaccine provided 100% protection for dogs following a two-dose regimen (D0-D7), whereas commercially approved inactivated vaccine offered 83% protection. After storage at 2–8 °C for 12 months, no notable changes were observed in the particle size, encapsulation efficiency, and integrity of mRNA or in the immunogenicity of the lyophilized vaccine. Conclusions: This study successfully developed a formulation and process of freeze-drying for a rabies mRNA vaccine, paving the way for future lyophilized mRNA vaccine development. Full article

(This article belongs to the Special Issue The Development of mRNA Vaccines)

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12 pages, 800 KiB

Open AccessArticle

The Role of Anti-Interferon-α Autoantibodies in Severe COVID-19: Implications for Vaccination Prioritization

by Xin Rong Lim, Shiyu Liu, Hwee Siew Howe, Khai Pang Leong, Elampirai Elangovan, Chiung-Hui Huang, Kok Ooi Kong, Bernard Yu Hor Thong, Shawn Vasoo and Bernard Pui Lam Leung

Vaccines 2025, 13(7), 742; https://doi.org/10.3390/vaccines13070742 - 9 Jul 2025

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Abstract

Background/Objectives: Neutralizing autoantibodies against type I interferons, particularly interferon-alpha (IFN-α), have been implicated in severe COVID-19 outcomes. This study investigated the prevalence and functional significance of anti-IFN-α autoantibodies (AAbs) in hospitalized unvaccinated COVID-19 patients and their association with COVID-19 disease severity. Methods [...] Read more.

Background/Objectives: Neutralizing autoantibodies against type I interferons, particularly interferon-alpha (IFN-α), have been implicated in severe COVID-19 outcomes. This study investigated the prevalence and functional significance of anti-IFN-α autoantibodies (AAbs) in hospitalized unvaccinated COVID-19 patients and their association with COVID-19 disease severity. Methods: We retrospectively analyzed serum samples from 122 hospitalized COVID-19 patients (asymptomatic/mild: n = 69, moderate: n = 35, severe/critical: n = 18) and 32 healthy uninfected controls. Anti-IFN-α AAbs were quantified using a commercial enzyme-linked immunosorbent assay (ELISA) kit, with functional neutralization assessed via competitive ELISA and STAT1 phosphorylation inhibition. Statistical comparisons were performed using one-way ANOVA for parametric data and the Kruskal–Wallis test for non-parametric variables. Results: Anti-IFN-α AAbs were detected in 24.6% of COVID-19 patients, with all clinical subgroups showing significantly higher titers compared to healthy controls (p < 0.05). Although no significant differences in anti-IFN-α AAb levels were found between mild, moderate, and severe cases, patients with severe or critical COVID-19 had markedly higher mean titers (10,511.3 ng/mL) compared to non-severe (mild + moderate) cases (375.2 ng/mL, p < 0.001). Strongly neutralizing anti-IFN-α AAbs, with high titers (>20,000 ng/mL) and the ability to inhibit STAT1 phosphorylation, were identified in three severe COVID-19 cases. Anti-IFN-α AAb levels correlated positively with CRP (r = 0.80, p < 0.0001), LDH (r = 0.80, p = 0.001), and neutrophil count (r = 0.52, p = 0.003), and negatively with lymphocyte count (r = −0.59, p = 0.0006). Conclusions: Elevated and functionally neutralizing anti-IFN-α AAbs were associated with severe COVID-19. These findings support their role as a risk factor for poor outcomes and emphasize the importance of early COVID-19 vaccination. Screening may help identify high-risk individuals, particularly those unvaccinated or with immune vulnerabilities. Full article

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

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11 pages, 468 KiB

Open AccessArticle

Seroprevalence of RSV IgG Antibodies Across Age Groups in Poland After the COVID-19 Pandemic: Data from the 2023/2024 Epidemic Season

by Barbara Poniedziałek, Wiktoria Majewska, Katarzyna Kondratiuk, Aleksander Masny, Anna Poznańska, Karol Szymański, Katarzyna Łuniewska, Emilia Czajkowska, Bartosz Mańkowski, Lidia B. Brydak, Krzysztof Tomasiewicz, Robert Flisiak and Piotr Rzymski

Vaccines 2025, 13(7), 741; https://doi.org/10.3390/vaccines13070741 - 9 Jul 2025

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Abstract

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections across all age groups, with the greatest burden observed in young children and older adults. The COVID-19 pandemic significantly disrupted RSV circulation, resulting in an immunity gap and altered transmission dynamics. [...] Read more.

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections across all age groups, with the greatest burden observed in young children and older adults. The COVID-19 pandemic significantly disrupted RSV circulation, resulting in an immunity gap and altered transmission dynamics. This study aimed to assess the seroprevalence of anti-RSV IgG antibodies in the Polish population during the 2023/2024 epidemic season. To our knowledge, this is the first study to characterize RSV seroprevalence at the population level in Poland. Methods: A total of 700 serum samples from individuals across different age groups were analyzed using a commercial assay to detect anti-RSV IgG antibodies. Seroprevalence and antibody levels, expressed as the index of positivity (IP), were examined by age and sex. Results: The overall seroprevalence of anti-RSV IgG antibodies was 91.4%. Antibody positivity increased markedly from 35.5% in infants aged 0–1 years to over 90% in children aged 4–5 years, reaching nearly universal levels in older age groups, including 99.1% in adults aged ≥60 years. Median IP values also rose with age, peaking in individuals aged ≥60 years. No significant differences in seroprevalence were observed between sexes, though older men showed slightly higher median IP values, potentially reflecting greater cumulative RSV exposure. Conclusions: This study provides key insights into the post-pandemic landscape of RSV immunity in Poland. The high seroprevalence across most age groups underscores widespread prior exposure, while the lower rates in infants highlight a continued vulnerability. These findings support the development and implementation of targeted immunization strategies, particularly for infants and older adults. Full article

(This article belongs to the Section Epidemiology and Vaccination)

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23 pages, 1777 KiB

Open AccessArticle

Challenges and Lessons Learned from a Field Trial on the Understanding of the Porcine Respiratory Disease Complex

by Elisa Crisci, Andrew R. Kick, Lizette M. Cortes, John J. Byrne, Amanda F. Amaral, Kim Love, Hao Tong, Jianqiang Zhang, Phillip C. Gauger, Jeremy S. Pittman and Tobias Käser

Vaccines 2025, 13(7), 740; https://doi.org/10.3390/vaccines13070740 - 9 Jul 2025

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Abstract

Background/Objectives: The porcine respiratory disease complex (PRDC) is a multifaceted, polymicrobial syndrome resulting from a combination of environmental stressors, primary infections (e.g., PRRSV) and secondary infectious agents (viruses and bacteria). PRDC causes severe lung pathology, leading to reduced performance, increased mortality rates, and [...] Read more.

Background/Objectives: The porcine respiratory disease complex (PRDC) is a multifaceted, polymicrobial syndrome resulting from a combination of environmental stressors, primary infections (e.g., PRRSV) and secondary infectious agents (viruses and bacteria). PRDC causes severe lung pathology, leading to reduced performance, increased mortality rates, and higher production costs in the global pig industry. Our goal was to conduct a comprehensive study correlating both the anti-PRRSV immune response and 21 secondary infectious agents with PRDC severity. Methods: To this end, PRRSV-negative weaners were vaccinated with a PRRSV-2 MLV and put into a farm with a history of PRDC. Subsequently, anti-PRRSV cellular and antibody responses were monitored pre-vaccination, at 28 days post vaccination (dpv) and during PRDC outbreak (49 dpv). NanoString was used to quantify 21 pathogens within the bronchoalveolar lavage (BAL) at the time of necropsy (51 dpv). PRRSV-2 was present in 53 out of 55 pigs, and the other five pathogens (PCMV, PPIV, B. bronchiseptica, G. parasuis, and M. hyorhinis) were detected in BAL samples. Results: Although the uncontrolled settings of field trials complicated data interpretation, multivariate correlation analyses highlighted valuable lessons: (i) high weaning weight predicted animal resilience to disease and high weight gains correlated with the control of the PRRSV-2 field strain; (ii) most pigs cleared MLV strain within 7 weeks, and the field PRRSV-2 strain was the most prevalent lung pathogen during PRDC; (iii) all pigs developed a systemic PRRSV IgG antibody response which correlated with IgG and IgA levels in BAL; (iv) the induction of anti-field strain-neutralizing antibodies by MLV PRRSV-2 vaccination was both late and limited; (v) cellular immune responses were variable but included strong systemic IFN-γ production against the PRRSV-2 field strain; (vi) the most detected lung pathogens correlated with PRRSV-2 viremia or lung loads; (vii) within the six detected pathogens, two viruses, PRRSV-2 and PCMV, significantly correlated with the severity of the clinical outcome. Conclusions: While a simple and conclusive answer to the multifaceted nature of PRDC remains elusive, the key lessons derived from this unique study provide a valuable framework for future research on porcine respiratory diseases. Full article

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

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12 pages, 747 KiB

Open AccessArticle

Nuclear Factor Erythroid 2-Related Factor 2 and SARS-CoV-2 Infection Risk in COVID-19-Vaccinated Hospital Nurses

by Stefano Rizza, Luca Coppeta, Gianluigi Ferrazza, Alessandro Nucera, Maria Postorino, Andrea Quatrana, Cristiana Ferrari, Rossella Menghini, Susanna Longo, Andrea Magrini and Massimo Federici

Vaccines 2025, 13(7), 739; https://doi.org/10.3390/vaccines13070739 - 9 Jul 2025

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Abstract

Background/Objectives: The COVID-19 pandemic has caused sickness and death among many health care workers. However, the apparent resistance of health care workers to SARS-CoV-2 infection despite their high-risk work environment remains unclear. To investigate if inflammation and circadian disruption contribute to resistance [...] Read more.

Background/Objectives: The COVID-19 pandemic has caused sickness and death among many health care workers. However, the apparent resistance of health care workers to SARS-CoV-2 infection despite their high-risk work environment remains unclear. To investigate if inflammation and circadian disruption contribute to resistance or diminished susceptibility to the SARS-CoV-2 virus, we retrospectively evaluated a cohort of volunteer hospital nurses (VHNs). Methods: A total of 246 apparently healthy VHNs (mean age 37.4 ± 5.9 years) who had received the BNT162b2 mRNA vaccine were asked to report their sleep quality, according to the Pittsburgh Sleep Quality Index, and number of SARS-CoV-2 infections during the observational study period (from the end of December 2020 to April 2025). The expression of inflammation-associated mediators and circadian transcription factors in peripheral blood mononuclear cells, as well as sleep quality, were examined. Results: Our findings revealed no anthropometric, biochemical, or inflammation-associated parameters but demonstrated significantly greater levels of NFE2L2, also known as nuclear factor erythroid-derived 2-like 2 (NFR2), gene expression in peripheral blood mononuclear cells among VHNs who had never been infected with SARS-CoV-2 (n = 97) than in VHNs with only one (n = 119) or with two or more (n = 35) prior SARS-CoV-2 infections (p < 0.01). This result was confirmed through one-to-one propensity score matching (p < 0.01). Moreover, NRF2 gene expression was not associated with the number of COVID-19 vaccinations (p = 0.598). Finally, NRF2 gene expression was higher among participants who reported better sleep quality (p < 0.01). Conclusions: Our findings suggest possible interactions among NRF2 gene expression, protection against SARS-CoV-2 infection, and the modulation of COVID-19 vaccination efficacy. Full article

(This article belongs to the Special Issue SARS-CoV-2 Pathogenesis, Vaccines and Therapeutics)

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20 pages, 3946 KiB

Open AccessArticle

Immune Durability and Breakthrough Infections 15 Months After SARS-CoV-2 Boosters in People over 65: The IMMERSION Study

by Concepció Violán, Bibiana Quirant-Sánchez, Maria Palau-Antoja, Dolors Palacin, Edwards Pradenas, Macedonia Trigueros, Guillem Pera, Gemma Molist, Gema Fernández-Rivas, Marc Boigués, Mar Isnard, Nuria Prat, Meritxell Carmona-Cervelló, Noemi Lamonja-Vicente, Brenda Biaani León-Gómez, Eva María Martínez-Cáceres, Pere Joan Cardona, Julià Blanco, Marta Massanella and Pere Torán-Monserrat

Vaccines 2025, 13(7), 738; https://doi.org/10.3390/vaccines13070738 - 9 Jul 2025

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Abstract

Background: SARS-CoV-2 booster vaccination remains essential to prevent severe COVID-19, particularly in vulnerable populations such as older adults. This study evaluated the durability and dynamics of immune responses following booster vaccination(s) in >65-year-old individuals and examined their association with protection against new [...] Read more.

Background: SARS-CoV-2 booster vaccination remains essential to prevent severe COVID-19, particularly in vulnerable populations such as older adults. This study evaluated the durability and dynamics of immune responses following booster vaccination(s) in >65-year-old individuals and examined their association with protection against new infections. Methods: Immune responses were evaluated at 3, 9, and 15 months post-booster, measuring SARS-CoV-2-specific IgG antibodies against spike [IgG(S)] and nucleocapsid [IgG(N)] proteins, neutralizing activity against the Omicron BA.2 variant, and cellular immunity. A subset of participants was tested before booster administration. Regression analyses examined the influence of clinical and immunological factors—including a bivalent fourth dose—on infection risk over time. Results: Booster vaccination significantly enhanced IgG(S) and neutralizing capacity, peaking at 3 months. Although a decline was observed by 9 months, responses remained above baseline. Individuals with prior SARS-CoV-2 infection exhibited higher IgG(S) levels and neutralizing titers, and significantly lower reinfection rates (15%), compared to uninfected individuals. A fourth vaccine dose further increased IgG(S) levels. While neutralizing capacity was not consistently enhanced by the fourth dose, recipients experienced a lower rate of new infections. Immune trajectory analyses revealed that breakthrough infections elicited strong humoral responses comparable to those seen in previously infected individuals, highlighting the role of hybrid immunity. Conclusions: In older adults, booster vaccination induces durable immune responses, with hybrid immunity offering enhanced protection. A fourth dose boosts antibody levels and reduces infection risk, supporting its use in this high-risk group. Continued monitoring is needed to determine the long-term effectiveness of boosters, particularly against emerging variants. Full article

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

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11 pages, 662 KiB

Open AccessArticle

Antibody Responses Following Primary Immunization with the Recombinant Herpes Zoster Vaccine (Shingrix^®) in VZV Seronegative Immunocompromised Adults

by Andrea Wessely, Ines Zwazl, Melita Poturica, Lukas Weseslindtner, Michael Kundi, Ursula Wiedermann and Angelika Wagner

Vaccines 2025, 13(7), 737; https://doi.org/10.3390/vaccines13070737 - 8 Jul 2025

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Abstract

Background: Immunocompromised patients are at risk of severe varicella zoster virus (VZV) infection and reactivation. In VZV seronegative immunocompromised persons, live-attenuated VZV vaccination is contraindicated, thus the recombinant herpes zoster vaccine (rHZV) remains a safe alternative, although an off-label application. Yet, data on [...] Read more.

Background: Immunocompromised patients are at risk of severe varicella zoster virus (VZV) infection and reactivation. In VZV seronegative immunocompromised persons, live-attenuated VZV vaccination is contraindicated, thus the recombinant herpes zoster vaccine (rHZV) remains a safe alternative, although an off-label application. Yet, data on the induction of a VZV-specific immune response in immunocompromised individuals with VZV-specific IgG below the assay’s cut-off are only available for patients after solid-organ transplantation (SOT). Methods: We retrospectively analyzed the induction of VZV-specific IgG antibody levels after vaccination with rHZV in immunocompromised patients who previously tested anti-VZV-IgG negative between March 2018 and January 2024. Results: Of 952 vaccinees screened that received 2 or 3 doses rHZV, depending on the underlying disease, 33 patients (median age 53.0; 51.5% female) with either hematopoietic stem cell transplantation (82%) or high-grade immunosuppressive treatment (18%) fulfilled the inclusion criteria. Upon rHZV vaccination, 88% (29/33) individuals mounted a significant antibody response exceeding the assay’s cut-off level for seropositivity (p < 0.0001). We detected higher geometric mean antibody concentrations after three compared to two doses. However, 12% remained below the assay’s cut-off level and were therefore considered non-responsive. Conclusions: The rHZV is immunogenic in VZV-seronegative immunocompromised individuals and therefore presents a valid option to induce seroconversion. However, antibody testing in high-risk groups should be considered to identify humoral non- and low responders. Full article

(This article belongs to the Special Issue Varicella and Zoster Vaccination)

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17 pages, 2146 KiB

Open AccessArticle

Development of an Effective Single-Dose PCV2/CSFV Bivalent Subunit Vaccine Against Classical Swine Fever Virus and Porcine Circovirus Type 2

by Yu-Chieh Chen, Wen-Bin Chung, Hso-Chi Chaung, Yen-Li Huang, Chi-Chih Chen and Guan-Ming Ke

Vaccines 2025, 13(7), 736; https://doi.org/10.3390/vaccines13070736 - 8 Jul 2025

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Abstract

Background/Objectives: Porcine Circovirus Type 2 (PCV2) impairs pigs’ immune systems and increases susceptibility to co-infections, including Classical Swine Fever (CSF), a highly contagious disease listed by the World Organisation for Animal Health (WOAH) as notifiable. Therefore, swine operations in CSF-endemic regions are [...] Read more.

Background/Objectives: Porcine Circovirus Type 2 (PCV2) impairs pigs’ immune systems and increases susceptibility to co-infections, including Classical Swine Fever (CSF), a highly contagious disease listed by the World Organisation for Animal Health (WOAH) as notifiable. Therefore, swine operations in CSF-endemic regions are encouraged to immunize piglets with both PCV2 and CSFV vaccinations. Currently, there is no commercially available bivalent vaccine for PCV2/CSFV. Methods: In this study, a total of twenty 4-week-old SPF pigs were administered our formulated PCV2/CSFV bivalent subunit vaccine, containing soluble CSFV-E2 (50 µg) and PCV2-ORF2 (100 µg) antigens with a porcine-specific CpG adjuvant. After 4 weeks of vaccination, all pigs were evaluated for efficacy against PCV2 and CSFV. Results: Pigs were only immunized once and showed significantly increased neutralizing or ELISA antibody titers against both viruses four weeks post-vaccination. After viral challenges, vaccinated pigs displayed no clinical signs or lesions and had markedly reduced CSFV and PCV2 viral loads in the serum and tissues compared to controls. Conclusions: These results demonstrate that a single dose of the PCV2/CSFV bivalent subunit vaccine is safe and effective in young pigs, induces strong antibody responses, and suppresses viral replication, making it a promising tool for swine disease control and cost-effective vaccination strategies. Full article

(This article belongs to the Special Issue Vaccination Against Major Respiratory Pathogens in Livestock Farming)

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14 pages, 823 KiB

Open AccessArticle

Long Term Outcomes of Anti-COVID-19 Vaccines in Patients with Systemic Lupus Erythematosus: A Multicentre Study

by Giovanni Benanti, Giuseppe A. Ramirez, Tommaso Schioppo, Lorenza Maria Argolini, Gabriella Moroni, Grazia Bonelli, Renato Alberto Sinico, Federico Alberici, Federica Mescia, Luca Moroni, Gabriele D. Gallina, Biancamaria Venerandi, Francesco Tamborini, Chiara Bellocchi, Lorenzo Beretta, Roberto Caporali, Enrica Bozzolo, Lorenzo Dagna and Maria Gerosa

Vaccines 2025, 13(7), 735; https://doi.org/10.3390/vaccines13070735 - 8 Jul 2025

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Abstract

Introduction: Systemic lupus erythematosus (SLE) is associated with infection-related morbidity. The risk of adverse outcomes secondary to infections was exacerbated during the recent COVID-19 pandemic, prompting mass vaccination with the novel mRNA-based and viral-vectored vaccines. Limited data exist on the long-term impact [...] Read more.

Introduction: Systemic lupus erythematosus (SLE) is associated with infection-related morbidity. The risk of adverse outcomes secondary to infections was exacerbated during the recent COVID-19 pandemic, prompting mass vaccination with the novel mRNA-based and viral-vectored vaccines. Limited data exist on the long-term impact of vaccination in patients with SLE. Methods: A post-vaccine group (PVG, n = 284) from a multicentric cohort of vaccinated patients with SLE from six tertiary referral centres in Northen Italy was compared with a control group (CG, n = 223) of similar demographics observed in the 2015–2019 period to investigate survival, hospitalisation, pregnancy, disease flare, disease progression, infection, and chronic complication accrual rates. Results: We did not observe excess SLE flares, SLE progression, hospitalisation, or pregnancy complications in the PVG. Cardiovascular complications due to comorbidities or to SLE were lower in the PVG than in the CG. Infections were more frequent in the PVG, related to COVID-19 in half of the cases, and were associated with SLE flares. Conclusions: Taken together, these data indicate that anti-COVID-19 vaccines are safe in the long-term when administered to patients with SLE. Stable, non-null rates of chronic comorbidity accrual and hospitalisation point out the existence of persistently unmet needs in patients with SLE. Full article

(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)

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16 pages, 654 KiB

Open AccessReview

Engaging Broader Stakeholders to Accelerate Group A Streptococcus Vaccine Development

by Dechuan Kong, Hao Pan, Huanyu Wu and Jian Chen

Vaccines 2025, 13(7), 734; https://doi.org/10.3390/vaccines13070734 - 7 Jul 2025

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Abstract

Group A Streptococcus (GAS) imposes a significant global health burden across all age groups, annually causing over 600 million cases of pharyngitis and more than 18 million severe invasive infections or sequelae. The resurgence of scarlet fever globally and streptococcal toxic shock syndrome [...] Read more.

Group A Streptococcus (GAS) imposes a significant global health burden across all age groups, annually causing over 600 million cases of pharyngitis and more than 18 million severe invasive infections or sequelae. The resurgence of scarlet fever globally and streptococcal toxic shock syndrome (STSS) outbreaks in Japan have brought GAS infections back into the spotlight as a pressing global health concern. Unfortunately, no licensed vaccine against GAS is yet available for clinical use. Our comprehensive review examines the developmental history of GAS vaccines, outlining the research trajectory from early inactivated vaccines to contemporary multivalent, conjugate, multi-antigen, and mRNA-based vaccine platforms. It systematically analyzes clinical trial outcomes of GAS vaccines, highlighting recent advances in both M protein-based and non-M protein vaccine candidates while summarizing promising target antigens. The review concludes with critical strategies to accelerate vaccine commercialization, including enhanced investment in research and development, expanded collaborations, leveraging advanced vaccine technologies, streamlined clinical trials, and strengthened public health advocacy. This review critically evaluates the current evidence and future prospects in GAS vaccine development, emphasizing innovative strategies and engaging broader stakeholders to accelerate GAS vaccine development. Full article

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

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23 pages, 1632 KiB

Open AccessReview

Retinal Vascular Occlusion Following COVID-19 Vaccination: A Comprehensive Review of Observational Study and Pathophysiological Mechanisms

by Yuchen Zhang, Haoliang Zhang, Kangjia Lv, Xin Lin, Feng’e Chen, Hui Cao and Chong Chen

Vaccines 2025, 13(7), 733; https://doi.org/10.3390/vaccines13070733 - 7 Jul 2025

Viewed by 268

Abstract

Background: Retinal vascular occlusion (RVO) and retinal artery occlusion (RAO) have been reported as rare adverse events following COVID-19 vaccination, raising concerns about vaccine safety. This review synthesizes cohort and case–control studies assessing the association between COVID-19 vaccines and RVO/RAO, while exploring [...] Read more.

Background: Retinal vascular occlusion (RVO) and retinal artery occlusion (RAO) have been reported as rare adverse events following COVID-19 vaccination, raising concerns about vaccine safety. This review synthesizes cohort and case–control studies assessing the association between COVID-19 vaccines and RVO/RAO, while exploring potential pathophysiological mechanisms. Methods: We analyzed large-scale population-based studies from South Korea, Europe, and the TriNetX database, focusing on odds ratios (OR), hazard ratios (HR), and relative risks (RR) across mRNA and adenoviral vector vaccines. Pathological processes were hypothesized based on molecular and clinical evidence. Results: Studies investigating the association between COVID-19 vaccination and retinal vascular occlusion show conflicting results; some studies report no association (e.g., OR 0.93, 95% CI 0.60–1.45), others suggest reduced risk (e.g., OR 0.80, 95% CI 0.64–0.99), and one indicates increased risk over two years (HR 2.19, 95% CI 2.00–2.39). Adenoviral vector vaccines, particularly ChAdOx1, show higher RAO incidence in specific cohorts. Proposed mechanisms include vaccine-induced immune thrombotic thrombocytopenia (VITT) via anti-PF4 antibodies, spike protein-mediated endothelial dysfunction, and adjuvant-driven inflammation. Conclusions: While causality remains unproven, temporal heterogeneity and vaccine type-specific risks warrant further investigation. Longitudinal studies with robust controls are needed to clarify these associations in the post-pandemic context. Full article

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

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16 pages, 470 KiB

Open AccessArticle

Factors Associated with Acceptance of Vaccination Against Human Papillomavirus in eThekwini District of South Africa

by Phelele Bhengu, Charles S. Wiysonge, Patrick D. M. C. Katoto, Duduzile Ndwandwe, Sara Cooper, Sebenzile Bhengu, Akhona V. Mazingisa, Theresa Saber, Mandisi Sithole, Darian Smith, Lindiwe G. Tembe, Paul Kuodi and Muki S. Shey

Vaccines 2025, 13(7), 732; https://doi.org/10.3390/vaccines13070732 - 6 Jul 2025

Viewed by 311

Abstract

Background: South Africa launched a school-based human papillomavirus (HPV) vaccination programme in 2014 and has achieved a national coverage of more than 80%. However, there is subnational variation in coverage, with eThekwini District in the province of KwaZulu-Natal having the lowest coverage at [...] Read more.

Background: South Africa launched a school-based human papillomavirus (HPV) vaccination programme in 2014 and has achieved a national coverage of more than 80%. However, there is subnational variation in coverage, with eThekwini District in the province of KwaZulu-Natal having the lowest coverage at 40%. Knowledge of the factors associated with vaccine acceptance in this district would inform tailored strategies to improve coverage, which could be extrapolated to similar settings. We conducted this cross-sectional study to assess the factors associated with HPV vaccine acceptance in eThekwini District. Methods: We used stratified random sampling to select caregivers of children aged 9–14 years in the district. We interviewed participants in April–May 2023 and employed bivariate and multivariate logistic regression models to assess the factors associated with HPV vaccine acceptance. Results: Of 793 individuals contacted, 713 (89.9%) participated. Most were women (86.1%) and had a mean age of 42.6 ± 11.6 years and secondary or lower education (83.8%). Most participants knew about the HPV vaccination programme (86.0%) and accepted HPV vaccination (93.5%). The latter includes 42.9% who had already vaccinated their daughters and 50.6% who were willing to allow their daughters to be vaccinated. A negligible proportion was either undecided (2.1%) or unwilling (4.4%) to accept HPV vaccination. Awareness of the programme (adjusted odds ratio [aOR] 5.22; 95% confidence interval [95%CI] 2.01–13.56), confidence in vaccine safety (aOR 19.69; 95%CI 5.86–66.15), and endorsement by religious leaders (aOR 5.06; 95%CI 1.56–16.45) were independent predictors of vaccine acceptance. Conclusions: Our findings highlight the critical role of the provision of information and education about the benefits and safety of HPV vaccination. Full article

(This article belongs to the Special Issue Vaccination Strategies and Population Immunity)

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15 pages, 1171 KiB

Open AccessArticle

Virus-like Particles Produced in the Baculovirus System Protect Hares from European Brown Hare Syndrome Virus (EBHSV) Infection

by Giulio Severi, Lucia Anzalone, Laura Madeo, Anna Serroni, Claudia Colabella, Antonella Di Paolo, Pier Mario Mangili, Elisabetta Manuali, Andrea Felici, Monica Cagiola, Antonio Lavazza, Lorenzo Capucci, Giovanni Pezzotti and Antonio De Giuseppe

Vaccines 2025, 13(7), 731; https://doi.org/10.3390/vaccines13070731 - 5 Jul 2025

Viewed by 263

Abstract

Background/Objectives: European Brown Hare Syndrome (EBHS) is an acute and highly contagious viral disease of hares that causes considerable economic losses on wild and captive-reared hares. No preventive treatments are currently available to defeat the disease. Immunoprophylactic and biosafety measures could be applied [...] Read more.

Background/Objectives: European Brown Hare Syndrome (EBHS) is an acute and highly contagious viral disease of hares that causes considerable economic losses on wild and captive-reared hares. No preventive treatments are currently available to defeat the disease. Immunoprophylactic and biosafety measures could be applied to prevent EBHS only in captive-reared hares, where vaccination is proposed as an effective strategy. Due to the lack of a cellular substrate for virus growth, commercially available vaccines are autovaccines produced from inactivated liver suspensions of hares dead for EBHS. Therefore, using a recombinant vaccine based on VP60 major capsid protein seems a viable alternative to overcome such a problem. Methods: the 6xHis C-terminal tagged VP60 protein of EBHSV was expressed and produced in baculovirus, purified by affinity chromatography and the self-assembled recombinant (rEVP60-His₆) protein. To establish the protective properties of rEVP60-His₆-based VLPs, hares were immunised with 50 and 100 µg of VLPs and parenterally challenged with EBHSV. Results: all hares vaccinated with 100 µg of VLPs survived after the experimental infection, demonstrating the excellent protective ability of this prototype VLPs-based vaccine. Conclusions: self-assembled EBHSV rEVP60-His₆ protein was successfully produced following a rapid, simple, low-cost protocol. Although the protective efficacy of such VLPs were experimentally demonstrated, some key aspects remain to be clarified, including the duration of protection, the entity of the antibody response, and the ability to stimulate cell-mediated response. Last, an additional aspect to be evaluated is whether the use of an adjuvant can determine whether its presence improves the performance of the recombinant VLPs vaccine. Full article

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

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21 pages, 492 KiB

Open AccessReview

Research Progress on Varicella-Zoster Virus Vaccines

by Hongjing Liu, Lingyan Cui, Sibo Zhang, Hong Wang, Wenhui Xue, Hai Li, Yuyun Zhang, Lin Chen, Ying Gu, Tingting Li, Ningshao Xia and Shaowei Li

Vaccines 2025, 13(7), 730; https://doi.org/10.3390/vaccines13070730 - 4 Jul 2025

Viewed by 419

Abstract

Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has [...] Read more.

Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has substantially reduced the global incidence of these diseases. However, live attenuated vaccines raise concerns regarding safety and immunogenicity, especially in immunocompromised populations, while recombinant subunit vaccines, such as Shingrix, exhibit high efficacy but are associated with side effects and adjuvant limitations. Recent advancements in vaccine technology, including mRNA vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines, offer promising alternatives with improved safety profiles and durable immunity. This review synthesizes current knowledge on VZV vaccine mechanisms, clinical applications, and immunization strategies, while also examining future directions in vaccine development. The findings underscore the pivotal role of VZV vaccines in disease prevention and highlight the need for continued research to enhance their public health impact. Full article

(This article belongs to the Special Issue Varicella and Zoster Vaccination)

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13 pages, 944 KiB

Open AccessReview

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

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

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

Viewed by 364

Abstract

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

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

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

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16 pages, 665 KiB

Open AccessArticle

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

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

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

Viewed by 382

Abstract

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

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

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

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24 pages, 732 KiB

Open AccessReview

Advances in Oncolytic Viral Therapy in Melanoma: A Comprehensive Review

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

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

Viewed by 540

Abstract

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

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

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

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11 pages, 538 KiB

Open AccessArticle

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

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

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

Viewed by 274

Abstract

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

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

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

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26 pages, 2069 KiB

Open AccessReview

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

by Ayman Elbehiry, Eman Marzouk and Adil Abalkhail

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

Viewed by 444

Abstract

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

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

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

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20 pages, 2293 KiB

Open AccessArticle

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

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

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

Viewed by 334

Abstract

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

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

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21 pages, 939 KiB

Open AccessReview

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

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

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

Viewed by 321

Abstract

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

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

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

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16 pages, 328 KiB

Open AccessArticle

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

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

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

Viewed by 352

Abstract

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

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

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

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13 pages, 3523 KiB

Open AccessArticle

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

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

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

Viewed by 277

Abstract

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

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

(This article belongs to the Section Veterinary Vaccines)

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4 pages, 156 KiB

Open AccessEditorial

Vaccines and Vaccination: Feature Papers

by Pedro Plans-Rubió

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

Viewed by 247

Abstract

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

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

12 pages, 329 KiB

Open AccessArticle

Enablers and Barriers of COVID-19 Vaccination in the Philippines

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

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

Viewed by 681

Abstract

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

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

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

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27 pages, 5667 KiB

Open AccessArticle

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

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

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

Viewed by 431

Abstract

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

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

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

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12 pages, 631 KiB

Open AccessReview

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

by Nicola Principi, Serafina Perrone and Susanna Esposito

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

Viewed by 422

Abstract

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

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

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

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Vaccines, Volume 13, Issue 7 (July 2025) – 85 articles

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