Vaccines

23 pages, 1684 KB

Open AccessArticle

Human Papillomavirus Vaccination Coverage Estimates Among the Primary Target Cohort (9–14-Year-Old Girls) in the World (2010–2024)

by Irena Ilic and Milena Ilic

Vaccines 2025, 13(10), 1010; https://doi.org/10.3390/vaccines13101010 (registering DOI) - 27 Sep 2025

Abstract

Background/Objectives: Monitoring human papillomavirus (HPV) vaccine coverage worldwide can provide valuable insight into cervical cancer prevention. The aim of this manuscript was to assess the HPV vaccination coverage among the primary target cohort (9–14-year-old girls) in the world from 2010 to 2024. [...] Read more.

Background/Objectives: Monitoring human papillomavirus (HPV) vaccine coverage worldwide can provide valuable insight into cervical cancer prevention. The aim of this manuscript was to assess the HPV vaccination coverage among the primary target cohort (9–14-year-old girls) in the world from 2010 to 2024. Methods: A descriptive epidemiological study (with an ecological study design) was carried out. Trends in HPV vaccination coverage were examined using the joinpoint regression analysis. Results: The HPV vaccination was introduced into the national schedule of 147 countries in 2024. Globally, coverage with the first dose of the HPV vaccine in the primary target cohort (9–14-year-old girls) was estimated at 56.9% in 2024. The growth trend in HPV vaccination coverage was significant mainly in the most developed countries (e.g., such as the USA, Canada and Germany), while trends were 10 times faster in other countries such as Armenia, Indonesia and Tanzania. A decline in trends of HPV vaccination coverage was significant in some developing countries (e.g., such as Panama, Sri Lanka, and Suriname) and in one of the most developed countries—the United Kingdom. Conclusions: A better understanding of changes in HPV vaccination coverage worldwide and further efforts to improve coverage to the target of 90% may contribute to more effective disease prevention. Full article

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

21 pages, 2156 KB

Open AccessArticle

Advancing Pyrogen Testing for Vaccines with Inherent Pyrogenicity: Development of a Novel Reporter Cell-Based Monocyte Activation Test (MAT)

by Sijia Yi, Jenny Xu, Liping Song, Frank Celeste, Christopher J. Wang and Melissa C. Whiteman

Vaccines 2025, 13(10), 1009; https://doi.org/10.3390/vaccines13101009 - 26 Sep 2025

Abstract

Background/Objectives: Pyrogens, fever-inducing substances from biological or environmental sources, are recognized by Toll-like receptors (TLRs) predominantly expressed by human monocytes and represent a critical quality attribute (CQA) for pharmaceutical safety. The rabbit pyrogen test (RPT), widely used for pyrogen assessment, suffers from high [...] Read more.

Background/Objectives: Pyrogens, fever-inducing substances from biological or environmental sources, are recognized by Toll-like receptors (TLRs) predominantly expressed by human monocytes and represent a critical quality attribute (CQA) for pharmaceutical safety. The rabbit pyrogen test (RPT), widely used for pyrogen assessment, suffers from high variability, limited accuracy, and poor reproducibility, particularly for vaccines containing inherent pyrogens such as outer membrane protein complex (OMPC)-based vaccines. Existing in vitro alternatives using peripheral blood mononuclear cells (PBMCs) are challenged by donor-to-donor variability and the operational complexity of ELISA readouts. To support the 3Rs (Refinement, Reduction, Replacement) and provide a more reliable quality control (QC) method, we developed a reporter cell–based monocyte activation test (MAT) suitable for release testing. Methods: We screened human monocytic reporter cell lines engineered with NFκB-responsive promoter elements driving a luminescent reporter. Reporter cells were treated with diverse endotoxin and non-endotoxin pyrogens and luminescence was quantified after stimulation. Selected THP-1-derived reporter cells were used to develop an MAT for OMPC. Assay performance was evaluated following validation guidelines: linearity, accuracy, precision, analytical range (relative to a reference lot), and robustness under deliberate parameter variations. Results: The THP-1 reporter cells could detect a wide range of pyrogens via simple luminescence readouts. For OMPC testing, the MAT demonstrated strong linearity (R² ≥ 0.99), accuracy with relative bias within ±10.3%, and high precision (overall %RSD ≤ 6.9%) across the 25–300% range. Deliberate variations in assay parameters did not materially affect performance, indicating robustness appropriate for routine release testing. Conclusions: The implementation of reporter cell-based MAT assays enhances consistency, reliability, and efficiency in evaluating the pyrogenicity and safety of drug products, supporting global initiatives to minimize animal testing while ensuring regulatory compliance. Full article

(This article belongs to the Special Issue Vaccines and Antibody-Based Therapeutics Against Infectious Disease)

► Show Figures

Figure 1

19 pages, 2191 KB

Open AccessArticle

Evaluation of Quillaja brasiliensis Saponin-Based Nanoparticles Combined with Leucine Aminopeptidases for Immunoprotection of Sheep Against Fasciola hepatica

by Jackeline Checa, Antonella Goyeche, Renzo Vettorazzi, Pablo Alonzo, Oscar Correa, Walter Norbis, Estela Castillo, Martin Cancela, Andrea Rossi, Fernando Silveira and Gabriela Maggioli

Vaccines 2025, 13(10), 1008; https://doi.org/10.3390/vaccines13101008 - 26 Sep 2025

Abstract

Background: Fasciola hepatica causes important economic losses in ruminants with only pharmacological treatments currently available, which produces several secondary problems. Because of this, vaccines have become an interesting alternative. Leucine aminopeptidases (LAPs) are attractive vaccine targets against fasciolosis since they play essential [...] Read more.

Background: Fasciola hepatica causes important economic losses in ruminants with only pharmacological treatments currently available, which produces several secondary problems. Because of this, vaccines have become an interesting alternative. Leucine aminopeptidases (LAPs) are attractive vaccine targets against fasciolosis since they play essential roles in the parasite such as host invasion and nutrient acquisition. To characterize immune responses, we produced two recombinant F. hepatica LAPs (FhLAP1 and FhLAP2), formulated with ISCOM-matrices (IMXs) nanoparticles from Quillaja brasiliensis saponins. Methods: Forty female Corriedale sheep were assigned to four groups (n = 10): FhLAP1/IMX, FhLAP1/FhLAP2/IMX, IMX (control), and FhLAP1/Adj50 (Adjuvac 50). Animals received two subcutaneous immunizations at weeks 0 and 4 and were challenged orally with 200 metacercariae at week 6. Results: FhLAP1 and FhLAP1/FhLAP2 induced specific IgG responses, with the predominance of the IgG1 response. However, these responses were lower than those generated by FhLAP1 formulated with Adj50. A qPCR analysis revealed that FhLAP1/IMX stimulated a Th1-type response profile before the challenge, but this profile was not sustained after infection. The post-infection profile of FhLAP1/FhLAP2/IMX was more congruent with expected values despite not achieving a robust IFN-γ expression. No significant differences in the fluke burden were observed. Conclusions: Further research on the optimal antigen/adjuvant combination in ruminants is encouraged. For instance, a higher concentration of adjuvant in the formulation used in this work may enhance the strength and duration of the inflammatory response and improve protective immunity against fasciolosis. Full article

(This article belongs to the Special Issue Parasitic Infections: Therapy for Host Immunity and Vaccination)

► Show Figures

Figure 1

18 pages, 11924 KB

Open AccessArticle

Next-Generation Sequencing Reveals Field Strain Dynamics and PRRSV-2 Clearance in Gilts When Using Tylvalosin During MLV Vaccination

by Weixin Wu, Xiang Gao, Junfeng Gao, Zhi Lai, Xiaohong Deng, Junnan Zhang, Qiongqiong Zhou and Lei Zhou

Vaccines 2025, 13(10), 1007; https://doi.org/10.3390/vaccines13101007 - 25 Sep 2025

Abstract

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses for the global swine industry. Gilt immunization using modified live virus (MLV) vaccines is crucial for herd stability, but it is complicated by frequent mixed infections of PRRSV strains on farm. [...] Read more.

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses for the global swine industry. Gilt immunization using modified live virus (MLV) vaccines is crucial for herd stability, but it is complicated by frequent mixed infections of PRRSV strains on farm. This study monitored the administration of tylvalosin during a PRRSV-2 MLV (TJM) immunization program, focusing on viral dynamics and immune responses in gilts naturally exposed to co-circulating classical (GD240101) and highly pathogenic like (HP-PRRSV-like, GD240102) PRRSV strains. Methods: The animal study was approved by the Laboratory Animal Ethical Committee of China Agricultural University. One hundred gilts were randomized into control and tylvalosin groups (n = 50/group). All received the TJM MLV vaccination. The tylvalosin group received tylvalosin tartrate premix cyclically in-feed for three cycles. Serum and saliva samples were collected periodically. PRRSV RNA (RT-qPCR) and specific antibodies (ELISA) were assessed. Viral population dynamics (relative abundance, mutation, recombination of TJM, GD240101, and GD240102) were monitored via next-generation sequencing (NGS) on a pooled PRRSV-positive sample. Results: In this field trial where tylvalosin was used, a shorter duration of PRRSV viremia and saliva shedding was observed to compare with controls. NGS analysis showed accelerated vaccine strain (TJM) clearance in the tylvalosin group (by week 3 vs. week 9 in control). Field strain dynamics were also altered, showing a faster decline in the tylvalosin group. Antibody response uniformity was altered, with lower coefficient of variation (CV) for PRRSV and CSFV observed following tylvalosin usage. Conclusions: In gilts receiving tylvalosin for the management of bacterial pathogens during a PRRSV MLV immunization program, it was associated with accelerated viral clearance and enhanced systemic immune response uniformity under mixed-infection field conditions. NGS provides invaluable data for dissecting these complex viral dynamics. Crucially, these findings describe a biological drug–host–virus interaction and should not be interpreted as an endorsement for the prophylactic use of antimicrobials. In alignment with global antimicrobial stewardship principles, tylvalosin should be reserved for the therapeutic treatment of diagnosed bacterial diseases to mitigate the risk of promoting resistance. Full article

(This article belongs to the Section Veterinary Vaccines)

► Show Figures

Figure 1

14 pages, 1911 KB

Open AccessArticle

Productivity Improvement of Human Papillomavirus-like Particles in Insect Cells Using Hyper-Expression Baculovirus Vector

by Jae-Bang Choi, Ji-Hoon Lee, Eun-Ha Kim, Jae-Deog Kim, Seong-Yeong Kim, Jong-Min Oh, Soo-Dong Woo, Hyunil Kim and Beom-Ku Han

Vaccines 2025, 13(10), 1006; https://doi.org/10.3390/vaccines13101006 - 25 Sep 2025

Abstract

Background/Objectives: Virus-like particle (VLP) vaccines based on human papillomavirus (HPV) L1 proteins have high efficacy for preventing cervical cancer and other HPV-associated diseases. The production yields of commercial HPV VLPs remain suboptimal. We aimed to improve HPV VLP production efficiency using a [...] Read more.

Background/Objectives: Virus-like particle (VLP) vaccines based on human papillomavirus (HPV) L1 proteins have high efficacy for preventing cervical cancer and other HPV-associated diseases. The production yields of commercial HPV VLPs remain suboptimal. We aimed to improve HPV VLP production efficiency using a hyper-expression vector system for the expression of L1 proteins of four major HPV serotypes—HPV 6, 11, 16, and 18. Methods: HPV L1 proteins were expressed in Trichoplusia ni (Hi5) insect cells via a hyper-expression baculovirus vector system. Following cell lysis using a microfluidizer, VLPs were purified through a two-step chromatographic process. Particle morphology was characterized using transmission electron microscopy and dynamic light scattering. Immunogenicity was evaluated using a murine model; mice received three intramuscular injections of the purified quadrivalent VLPs. The resulting IgG and neutralizing antibody responses were compared with those elicited by the commercial quadrivalent vaccine, Gardasil. Results: The L1 proteins from HPV 6, 11, 16, and 18 were successfully expressed at high levels in Hi5 cells, forming uniformly sized VLPs with hydrodynamic diameters of 50–60 nm. The average production yield of the quadrivalent VLPs exceeded 40 mg/L, an improvement over conventional yields. The candidate VLPs elicited strong HPV-specific IgG and neutralizing antibody responses in mice, comparable to those induced by Gardasil. Conclusions: The hyper-expression baculovirus vector system enables high-yield production of HPV L1 VLPs with desirable structural and immunogenic properties. This approach holds promise for the cost-effective and scalable manufacturing of next-generation HPV VLP vaccines, facilitating broader global access to HPV immunization. Full article

(This article belongs to the Special Issue Cost-Effectiveness of Vaccines and Public Health)

► Show Figures

Figure 1

1 pages, 121 KB

Open AccessCorrection

Correction: Plans-Rubió, P. Vaccines and Vaccination: Feature Papers. Vaccines 2025, 13, 720

by Pedro Plans-Rubió

Vaccines 2025, 13(10), 1005; https://doi.org/10.3390/vaccines13101005 - 25 Sep 2025

Abstract

The author would like to make the following correction to this publication [...] Full article

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

20 pages, 1816 KB

Open AccessArticle

Restricting O-Linked Glycosylation of the Mucin-like Domains Enhances Immunogenicity and Protective Efficacy of a Respiratory Syncytial Virus G Glycoprotein Vaccine Antigen

by Sara M. O’Rourke, Jackelyn Murray, Maria G. Juarez, Ralph A. Tripp and Rebecca M. DuBois

Vaccines 2025, 13(10), 1004; https://doi.org/10.3390/vaccines13101004 - 25 Sep 2025

Abstract

Background: As of 2024, three approved respiratory syncytial virus (RSV) vaccines are licensed for use in adults in the United States: Arexvy™, Abrysvo™, and mRESVIA™. These vaccines are specifically designed to prevent lower respiratory tract disease caused by RSV in adults aged 60 [...] Read more.

Background: As of 2024, three approved respiratory syncytial virus (RSV) vaccines are licensed for use in adults in the United States: Arexvy™, Abrysvo™, and mRESVIA™. These vaccines are specifically designed to prevent lower respiratory tract disease caused by RSV in adults aged 60 and older. All licensed vaccines rely on stabilized RSV pre-fusion F (pre-F) as the sole antigen. RSV vaccines targeted to the other key RSV surface protein, the G glycoprotein, have been slow to advance because of sequence diversity and a historical association with vaccine-enhanced disease in animal models of infection. The recent development of structure-guided subunit immunogens and immune-modulating adjuvants has renewed interest in RSV G, as the combination of both F and G glycoproteins appears to improve vaccine efficacy over either one individually. RSV G is extensively O-glycosylated, with two mucin-like regions. Methods: This study investigated the effects of manipulation of O-linked glycosylation on a recombinant RSV G vaccine antigen in an RSV/A2 challenge study in BALB/c mice. Conclusions: We found that restricting the O-linked glycosylation on a recombinant RSV G vaccine antigen enhances its immunogenicity and protective efficacy in BALB/c mice. Full article

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

► Show Figures

Figure 1

18 pages, 1585 KB

Open AccessReview

Understanding Vaccine Hesitancy: Insights and Improvement Strategies Drawn from a Multi-Study Review

by Kaitlin (Quirk) Brumbaugh, Frances Gellert and Ali H. Mokdad

Vaccines 2025, 13(10), 1003; https://doi.org/10.3390/vaccines13101003 - 25 Sep 2025

Abstract

Vaccines are among the most effective public health interventions, significantly reducing morbidity and mortality from infectious diseases. Despite their proven efficacy, vaccine hesitancy has emerged as a pressing global challenge. This review examines the drivers, barriers, and interventions associated with vaccine hesitancy and [...] Read more.

Vaccines are among the most effective public health interventions, significantly reducing morbidity and mortality from infectious diseases. Despite their proven efficacy, vaccine hesitancy has emerged as a pressing global challenge. This review examines the drivers, barriers, and interventions associated with vaccine hesitancy and uptake, focusing on childhood vaccinations and the role of parents as primary decision-makers. Misinformation, safety concerns, and political decisions have contributed to declining vaccination rates, posing threats to public health. The article proposes targeted programs and policies to rebuild vaccine confidence, emphasizing the role of trusted messengers, health literacy, and structural reforms to reduce barriers. Recommendations highlight the importance of accurate information, open communication, and advocacy for school vaccine mandates. The conclusion stresses the urgent need to implement robust policies and community-based initiatives to ensure widespread immunization and safeguard population health. Full article

(This article belongs to the Special Issue Impact of Immunization Safety Monitoring on Vaccine Coverage)

► Show Figures

Figure 1

13 pages, 529 KB

Open AccessReview

The Experience of an Accelerated COVID-19 Immunization Campaign in Oman: A Review Within the WHO Health System Building Blocks Framework

by Thamra Al Ghafri, Lamya Al Balushi, Zainab Al Balushi, Lamees Al Kiyumi, Asma Bait Ishaq and Jannat Al Harthi

Vaccines 2025, 13(10), 1002; https://doi.org/10.3390/vaccines13101002 - 25 Sep 2025

Abstract

Oman launched its COVID-19 vaccination campaign in December 2020, navigating significant public health challenges with resilience and adaptability. The country faced global vaccine shortages, community hesitancy to receive the vaccine, and diverse sociocultural and infrastructural obstacles. Despite these issues, Oman scaled up its [...] Read more.

Oman launched its COVID-19 vaccination campaign in December 2020, navigating significant public health challenges with resilience and adaptability. The country faced global vaccine shortages, community hesitancy to receive the vaccine, and diverse sociocultural and infrastructural obstacles. Despite these issues, Oman scaled up its COVID-19 vaccination efforts, administering over 7 million doses, covering approximately 71% of the population by mid-2022. The campaign, which operated through more than 44 vaccination centers nationwide, exemplified rapid vaccine implementation, strategic prioritization, and a coordinated pandemic response. This study examined the field experience of Oman’s accelerated COVID-19 mass vaccination campaign through the World Health Organization’s Health System Building Blocks framework. The key domains addressed included (1) multi-sectoral collaboration underpinned by strong governance structures; (2) the role of primary healthcare facilities as essential first responders during health crises, and safe handling of vaccination procedures; (3) transparency and active community engagement, particularly through local leaders and social media, to address vaccine hesitancy; (4) the integration of digital health information systems to ensure unified and efficient data management; (5) building a resilient healthcare workforce by enhancing vaccination capacity and mental health support; and (6) the importance of financial alternatives. Additionally, the critical role of global and regional partnerships in vaccine production and distribution was highlighted. Drawing on Oman’s experience, this descriptive review offers context-specific lessons for enhancing health system preparedness and guiding effective responses to public health emergencies. Full article

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

► Show Figures

Figure 1

21 pages, 5645 KB

Open AccessSystematic Review

Multilevel Interventions Aimed at Improving HPV Immunization Coverage: A Systematic Review and Meta-Analysis

by Irena Ilic, Vladimir Jakovljevic, Mario Gajdacs, Edit Paulik and Milena Ilic

Vaccines 2025, 13(10), 1001; https://doi.org/10.3390/vaccines13101001 - 25 Sep 2025

Abstract

Background/Objectives: Human papillomavirus (HPV)-attributable cancers are a major public health problem worldwide. However, HPV vaccination rates vary significantly and are often not optimal. This study aimed to assess the effects of multilevel interventions on improving HPV vaccination. Methods: A systematic literature review and [...] Read more.

Background/Objectives: Human papillomavirus (HPV)-attributable cancers are a major public health problem worldwide. However, HPV vaccination rates vary significantly and are often not optimal. This study aimed to assess the effects of multilevel interventions on improving HPV vaccination. Methods: A systematic literature review and a meta-analysis were carried out, taking into account randomized controlled trials. Outcomes of interest were HPV vaccination initiation and completion. A random-effect meta-analysis using the generic inverse variance method was carried out, with a risk ratio (RR) with a 95% confidence interval (CI) as the pooled effect estimate. Results: A literature search identified 15 relevant studies, all conducted in high-income countries. Multilevel interventions significantly improved HPV vaccination coverage and initiation (RR = 1.26, 95% CI 1.16–1.38, p < 0.00001 and RR = 1.14, 95% CI 1.04–1.24, p = 0.004, respectively) compared to usual care. Sensitivity analyses showed that the results remained relatively robust. Subgroup analysis by targeted levels of intervention indicated that multilevel interventions had an effect across all comparisons and outcomes except for HPV vaccination completion for interventions that targeted four levels of influence. Conclusions: Based on evidence from high-income settings, multilevel interventions are effective in improving HPV vaccination rates. Future studies should expand the focus to areas with limited resources too and aim to provide more detailed data, avoid registering outcomes via self-report, and create sustainable strategies that can persist beyond a study’s duration and possibly become part of policies for improving HPV vaccination coverage. Full article

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

► Show Figures

Figure 1

13 pages, 792 KB

Open AccessArticle

10-Year Effects of the 13-Valent Pneumococcal Conjugate Vaccine in Patients with Chronic Obstructive Pulmonary Disease and Stable Angina Pectoris

by Galina L. Ignatova, Sergey N. Avdeev, Vladimir N. Antonov, Elena V. Blinova and Mikhail V. Osikov

Vaccines 2025, 13(10), 1000; https://doi.org/10.3390/vaccines13101000 - 25 Sep 2025

Abstract

Background: COPD and stable angina are common in older adults, increasing the risk of respiratory and cardiovascular complications. Pneumococcal vaccination is recommended to reduce this burden. This study evaluated the 10-year impact of 13-valent pneumococcal conjugate vaccine (PCV13) on community-acquired pneumonia (COPD), [...] Read more.

Background: COPD and stable angina are common in older adults, increasing the risk of respiratory and cardiovascular complications. Pneumococcal vaccination is recommended to reduce this burden. This study evaluated the 10-year impact of 13-valent pneumococcal conjugate vaccine (PCV13) on community-acquired pneumonia (COPD), COPD exacerbations, hospitalizations, and survival in this cohort. Methods: A total of 483 male patients with COPD and/or stable angina received a single dose of PCV13 and were divided into three groups: Group 1 (n = 140): vaccinated with COPD; Group 2 (n = 167): vaccinated with COPD and stable angina; and Group 3 (n = 176): unvaccinated with COPD. Primary endpoints were CAP cases, COPD exacerbations, and hospitalizations; the secondary endpoint was survival. Analysis used generalized linear models, Cox regression, and Kaplan–Meier survival curves. Results: PCV13 significantly reduced CAP in patients with COPD alone but not in those with comorbid angina. Although CAP, exacerbations, and hospitalizations increased over time, vaccinated groups consistently showed lower rates than the unvaccinated group. Survival was higher in both vaccinated groups over 10 years. Conclusions: PCV13 was associated with a reduced risk of CAP, COPD exacerbations, hospitalizations, and improved survival in older adults with COPD and stable angina. These findings support the vaccine’s potential to improve outcomes in multimorbid populations and its inclusion in clinical guidelines and adult immunization programs for high-risk older adults. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

► Show Figures

Figure 1

21 pages, 4108 KB

Open AccessArticle

Respiratory Efficacy of a Multivalent Marker Vaccine Against Bovine Viral Diarrhoea Virus Types 1 and 2, Infectious Bovine Rhinotracheitis Virus, Bovine Respiratory Syncytial Virus, and Bovine Parainfluenza-3 Virus in Young Calves

by Carlos Montbrau, Marta Gibert, Marina Solé, Isabel Barril, Mercè Roca, Lucia Acal, Berta Vázquez, Joaquim Mallorqui and Ricard March

Vaccines 2025, 13(10), 999; https://doi.org/10.3390/vaccines13100999 - 24 Sep 2025

Viewed by 13

Abstract

Background/Objectives: A new multivalent vaccine (DIVENCE^® PENTA), containing Bovine viral diarrhoea virus (BVDV) types 1 and 2 recombinant proteins, live gE/tk double gene deleted Bovine Herpesvirus type 1 (BoHV-1 or IBR), live attenuated Bovine respiratory syncytial virus (BRSV) and inactivated parainfluenza-3 [...] Read more.

Background/Objectives: A new multivalent vaccine (DIVENCE^® PENTA), containing Bovine viral diarrhoea virus (BVDV) types 1 and 2 recombinant proteins, live gE/tk double gene deleted Bovine Herpesvirus type 1 (BoHV-1 or IBR), live attenuated Bovine respiratory syncytial virus (BRSV) and inactivated parainfluenza-3 virus (PI-3) has been designed to protect cattle against the main viral pathogens associated with Bovine respiratory disease (BRD). The aim of this study was to demonstrate the efficacy of DIVENCE^® PENTA against experimental infections with BVDV-1, BVDV-2, IBR, BRSV and PI-3 in young calves. Methods: Ten-week-old calves were given two intramuscular doses three weeks apart. The efficacy was evaluated by means of an experimental challenge three weeks after vaccination. Serology, clinical signs, rectal temperature, white blood cell count, viral shedding and lung lesions were monitored after the challenge. Results/Conclusions: The results demonstrated a significant sparing of BRD in calves vaccinated with DIVENCE^® PENTA, as evidenced by fewer clinical signs, lower rectal temperatures, reduced viral shedding and less severe pulmonary lesions compared to control animals. A significant reduction in hyperthermia, leukopenia and viraemia post-challenge was also observed, highlighting the efficacy of the multivalent vaccine against BVDV types 1 and 2, IBR, BRSV and PI-3 in young calves. Full article

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

► Show Figures

Figure 1

23 pages, 2210 KB

Open AccessArticle

Gender Dynamics in Vaccine Acceptance and Hesitancy Among Primary Caregivers in Ethiopia: A Mixed-Methods Study

by Geteneh Moges Assefa, Michael Tarekegn, Kasahun Negash, Betibebu Mulugeta, Sintayehu Abebe, Baye Denekew, Mhret Ayele, Azmeraw A. Tesfahun, Gedamu Kassie, Virginia Stulz, Makida Berhan and Muluken Desalegne Muluneh

Vaccines 2025, 13(10), 998; https://doi.org/10.3390/vaccines13100998 - 24 Sep 2025

Viewed by 50

Abstract

Background/Objectives: Vaccination uptake in Ethiopia is deeply shaped by gender norms, with women serving as primary caregivers but often limited by low autonomy, while men typically control household decisions but remain less engaged in child health. This study examines gendered influences on vaccine [...] Read more.

Background/Objectives: Vaccination uptake in Ethiopia is deeply shaped by gender norms, with women serving as primary caregivers but often limited by low autonomy, while men typically control household decisions but remain less engaged in child health. This study examines gendered influences on vaccine hesitancy and acceptance to inform future strategies. Methods: A community-based cross-sectional mixed-methods study was conducted in four regions of Ethiopia (Amhara, Oromia, Afar, and Tigray). Quantitative data were collected from 992 caregivers through multistage stratified sampling procedure, whereas qualitative data were collected from 26 in-depth interviews, 24 exit interviews and 11 key informant interviews and were analyzed thematically guided by the WHO Behavioural and Social Drivers framework. Multivariable logistic regression was conducted to determine the associations. Results: The result highlighted that the proportion of caregivers who reported willingness to vaccinate their child with all recommended vaccines was high (93.5%) and more likely among those with higher education, family support, religious support, and frequency of health worker contact. However, 51.1% of caregivers displayed some degree of vaccine hesitancy, with higher prevalence among males. Hesitancy was linked to traditional beliefs and norms that assign vaccination responsibility to mothers, urban residence, and being employed, while secondary education, family support, and religious support were protective. While acceptance is high, hesitancy persists. Gender roles, education, social support, and health worker engagement influence immunization outcomes. Conclusions: The study highlighted that expanding immunization across all age groups and reducing persistent hesitancy requires a shift toward gender-responsive strategies including integrating a gender perspective into the immunization programs that address traditional norms and misinformation. Full article

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

► Show Figures

Figure 1

16 pages, 1928 KB

Open AccessArticle

Dual-Function Adjuvant Cyclosporin A: Enhancing RSV-Specific Humoral Immunity via Treg-Driven B-Cell Activation

by Chaofan Li, Yiwei Zhong, Shuren Zhang, Caixia Su, Gan Zhao and Bin Wang

Vaccines 2025, 13(10), 997; https://doi.org/10.3390/vaccines13100997 - 23 Sep 2025

Viewed by 102

Abstract

Background: Respiratory syncytial virus (RSV) remains a leading cause of respiratory illness globally, with limited vaccine options, particularly for infants and high-risk populations. This study investigates Cyclosporin A (CsA), traditionally an immunosuppressant, as a novel adjuvant to enhance RSV-specific immunity. Methods: BALB/c mice [...] Read more.

Background: Respiratory syncytial virus (RSV) remains a leading cause of respiratory illness globally, with limited vaccine options, particularly for infants and high-risk populations. This study investigates Cyclosporin A (CsA), traditionally an immunosuppressant, as a novel adjuvant to enhance RSV-specific immunity. Methods: BALB/c mice were subcutaneously immunized with RSV G protein co-administered with varying Cyclosporin A doses, challenged intranasally with RSV, and analyzed for RSV-specific humoral immunity and mechanistic Treg-dependent B-cell responses. Results: We demonstrate that co-administration of CsA with the RSV G protein (G+CsA) dose-dependently boosts RSV-specific IgG and neutralizing antibodies, with selective augmentation of IgG1 and IgG2 subclasses. Mechanistically, G+CsA induces regulatory T cells (Tregs) expressing CD40L and IL-10, which directly promote B-cell activation, proliferation, and plasma cell differentiation. Depletion of Tregs or neutralization of IL-10/CD40L abrogated antibody production, confirming these pathways as critical mediators. Notably, G+CsA-induced Tregs adopt a helper phenotype distinct from conventional Tregs, balancing immune enhancement and homeostasis. Conclusions: CsA demonstrates dual adjuvant properties by enhancing RSV-specific neutralizing IgG titers through Treg-driven B-cell activation, offering a potential strategy to optimize vaccine-induced humoral immunity. Full article

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

► Show Figures

Figure 1

18 pages, 3230 KB

Open AccessArticle

Characterisation of Cell-Mediated Immunity Against Bovine Alphaherpesvirus 1 (BoAHV-1) in Calves

by Giulia Franzoni, Cecilia Righi, Immacolata De Donato, Giovanna Cappelli, Giovanna De Matteis, Eleonora Scoccia, Giulia Costantino, Emanuela Giaconi, Susanna Zinellu, Carlo Grassi, Alessandra Martucciello, Francesco Grandoni and Stefano Petrini

Vaccines 2025, 13(10), 996; https://doi.org/10.3390/vaccines13100996 - 23 Sep 2025

Viewed by 135

Abstract

Background: Bovine alphaherpesvirus 1 (BoAHV-1) is a major respiratory and reproductive pathogen in cattle worldwide. Both innate and adaptive immune responses contribute to protection against this virus; however, virus-host interactions remain partly undefined. In this study, the impact of BoAHV-1 infection [...] Read more.

Background: Bovine alphaherpesvirus 1 (BoAHV-1) is a major respiratory and reproductive pathogen in cattle worldwide. Both innate and adaptive immune responses contribute to protection against this virus; however, virus-host interactions remain partly undefined. In this study, the impact of BoAHV-1 infection on calves’ immune responses was investigated in detail. Methods: Six calves were intranasally infected with wild-type BoAHV-1, and blood samples were collected longitudinally. Leukocyte subset dynamics were assessed by complete haematological assay and flow cytometry, while multiplex ELISA was used to quantify serum levels of ten cytokines. For each parameter, post-infection values (days 2, 4, 8, 10, and 14) were compared with pre-infection baseline values (day 0). Results: Infection induced an initial phase of immunosuppression, reflected by decreased circulating αβ and γδ-T cells. However, infected animals rapidly developed a protective immune response, characterised by increased circulating classical and intermediate monocytes and elevated levels of the related chemokine MIP-1β. Early post-infection, rises in serum IFN-γ and IL-10 were also detected. Conclusions: Our data suggest that monocyte recruitment and increased serum levels of IFN-γ and IL-10 are positively associated with the ability to overcome infection. A better understanding of the immunopathogenic mechanisms underlying BoAHV-1 infection will support the development of more effective vaccines against this virus. Full article

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

► Show Figures

Figure 1

34 pages, 1154 KB

Open AccessReview

Bacillus subtilis Spores as a Vaccine Delivery Platform: A Tool for Resilient Health Defense in Low- and Middle-Income Countries

by Atiqah Hazan, Hai Yen Lee, Vunjia Tiong and Sazaly AbuBakar

Vaccines 2025, 13(10), 995; https://doi.org/10.3390/vaccines13100995 - 23 Sep 2025

Viewed by 259

Abstract

The COVID-19 pandemic exposed the urgent need for innovative tools to strengthen pandemic preparedness and health defense, especially in low- and middle-income countries (LMICs). While vaccination has been the cornerstone of the defense strategy against many infectious agents, there is a critical gap [...] Read more.

The COVID-19 pandemic exposed the urgent need for innovative tools to strengthen pandemic preparedness and health defense, especially in low- and middle-income countries (LMICs). While vaccination has been the cornerstone of the defense strategy against many infectious agents, there is a critical gap in vaccine equity, ensuring it is accessible to all, especially among the most vulnerable populations. The conventional vaccine delivery platforms, through parenteral administration, face notable limitations, including reliance on trained personnel, sterile conditions, and cold chain logistics. The parenteral vaccines often fail to induce robust mucosal immunity, which is critical for preventing infections at mucosal surfaces, the primary entry point for many pathogens. Bacillus subtilis, a Gram-positive, spore-forming bacterium, has emerged as a promising platform for mucosal vaccine delivery owing to its Generally Recognized as Safe (GRAS) status. Its robust spores are highly resilient to harsh environmental conditions, which may eliminate the need for cold chain storage and further facilitate distribution in LMICs. This review explores the potential of B. subtilis as a next-generation vaccine delivery platform, focusing on its unique characteristics, mechanisms of action, and applications in addressing global health challenges. This review also examines existing research demonstrating the safety, immunogenicity, and efficacy of B. subtilis spore-based vaccines while identifying limitations and future directions for optimization as a scalable and adaptable solution for resilient health defense, particularly in LMICs. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

► Show Figures

Figure 1

9 pages, 502 KB

Open AccessBrief Report

Serological Response After the Fourth Dose of COVID-19 Vaccine in Highly Immunosuppressed Patients

by Abelardo Claudio Fernández Chávez, Paula Navarro López, Ana De Andrés Martín, Daniel Leonardo Sánchez Carmona, Guillermo Yovany Ordoñez León and Jesús María Aranaz Andrés

Vaccines 2025, 13(10), 994; https://doi.org/10.3390/vaccines13100994 - 23 Sep 2025

Viewed by 158

Abstract

Introduction (Objectives): This study aimed to evaluate the serological response to a fourth dose of mRNA COVID-19 vaccine in patients with conditions that confer a high risk of severe disease, particularly those with high-level immunosuppression. Methods: An observational study was conducted at the [...] Read more.

Introduction (Objectives): This study aimed to evaluate the serological response to a fourth dose of mRNA COVID-19 vaccine in patients with conditions that confer a high risk of severe disease, particularly those with high-level immunosuppression. Methods: An observational study was conducted at the Ramón y Cajal University Hospital between February and August 2022. Adults (≥18 years) with high-risk conditions who had received four doses of either BNT162b2 or mRNA-1273 were included. Anti-spike IgG levels were measured ≥14 days post-vaccination. An adequate response was defined as an antibody concentration ≥260 BAU/mL. Results: A total of 943 patients were analyzed; 846 (89.7%) achieved an adequate response. In the bivariate analysis, patients aged 60–74 years had a higher risk of inadequate response compared to those aged 18–39 years (OR 1.824 vs. OR 0.257). Female sex was associated with a higher risk of inadequate response (OR 1.522; 95% CI: 0.974–2.371). In multivariable logistic regression, patients with high immunosuppression had a higher, though not statistically significant, risk of inadequate response compared with those without. Discussion: Our findings are consistent with international evidence suggesting that age and certain clinical factors reduce vaccine immunogenicity. The observed paradoxical effect of sex could reflect the higher prevalence of aggressive immunosuppressive therapies among women in the study cohort. Conclusions: Most immunosuppressed patients achieved seroconversion after the fourth dose. These results underscore the need for tailored vaccination strategies and additional measures in highly immunosuppressed subgroups. Full article

(This article belongs to the Special Issue Immunization of Immunosuppressed Patients)

► Show Figures

Figure 1

19 pages, 7196 KB

Open AccessArticle

Preclinical Immunogenicity Evaluation of a DTacP-sIPV/Hib Combination Vaccine in Rodent Models Under Varying Formulations and Immunization Schedules

by Yixian Fu, Wei Huang, Lukui Cai, Yan Ma, Qin Gu, Qiuyan Ji, Jingyan Li, Na Gao, Xiaoyu Wang, Guang Ji, Jiana Wen, Wenzhu Hu, Hongwei Liao, Ling Ping, Yuting Fu, Guoyang Liao, Lujie Yang, Shengjie Ouyang, Mingqing Wang, Xiaoyue He, Han Chu, Wenlu Kong, Xinhua Qin, Huimei Zheng, Jiangli Liang, Ting Zhao and Jingsi Yang Show full author list Hide full author list

Vaccines 2025, 13(10), 993; https://doi.org/10.3390/vaccines13100993 - 23 Sep 2025

Viewed by 164

Abstract

Background: Combination vaccines protecting against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b reduce injection burden and improve compliance. While widely used globally, no domestically produced pentavalent vaccine is currently licensed in China. Recent updates to China’s immunization schedule—including earlier initiation and [...] Read more.

Background: Combination vaccines protecting against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b reduce injection burden and improve compliance. While widely used globally, no domestically produced pentavalent vaccine is currently licensed in China. Recent updates to China’s immunization schedule—including earlier initiation and an added booster for pertussis—highlight the need for compatible combination vaccines. This study evaluated the immunogenicity and feasibility of a novel DTacP-sIPV/Hib candidate vaccine in preclinical models. Methods: The vaccine was assessed in NIH mice and Wistar rats. Two Hib dosages were tested in mice alongside a DTacP-wIPV/Hib vaccine (Pentaxim^®). In rats, two sIPV formulations (Formulations A and B) were administered using different intervals (1-month vs. 2-month) and injection methods (mixed vs. separate). Antibody titers were measured by ELISA and poliovirus neutralization assays. Results: The candidate vaccine elicited robust immune responses in both models. In mice, after three doses, the high-dose Hib group achieved >90% seroconversion for pertactin antigen, whereas the low-dose group reached 100% for all antigens. In rats, antibody responses after three doses were comparable to those induced by Pentaxim^®, with no significant differences between immunization schedules or administration routes. Compared with Formulation A (containing a higher type I sIPV antigen content), Formulation B exhibited reduced type I poliovirus neutralization after the first dose (p < 0.05) and delayed seroconversion, while responses to other antigens remained similar. Conclusion: The candidate DTacP-sIPV/Hib vaccine showed robust immunogenicity and flexibility across schedules and administration methods. A formulation including DT 12.5 Lf, TT 3.5 Lf, PT 25 μg, FHA 25 μg, PRN 8 μg, PRP 10 μg, and sIPV I/II/III at 30/32/45 DU is proposed for further development. Full article

(This article belongs to the Special Issue Vaccines and Antibody-Based Therapeutics Against Infectious Disease)

► Show Figures

Figure 1

4 pages, 130 KB

Open AccessEditorial

Special Issue: Vaccines and Vaccinations in the Pandemic

by Dimitrios Papagiannis and Georgios Rachiotis

Vaccines 2025, 13(10), 992; https://doi.org/10.3390/vaccines13100992 - 23 Sep 2025

Viewed by 134

Abstract

The rapid development of multiple COVID-19 vaccines—particularly through mRNA technology, though not limited to it—within a short period following the emergence of the virus was unprecedented [...] Full article

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

Journal Menu

Journal Browser

Vaccines, Volume 13, Issue 10 (October 2025) – 19 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI