Vaccines

21 pages, 2167 KB

Open AccessArticle

Mosquito Saliva Subunit Vaccine Enhances Efficacy of VLP Vaccines Against Zika and Chikungunya Viruses

by Siân Jossi, Megan Cole, Yonca Keskek Turk, Sam Verwimp, Katrien Trappeniers, James Luk, Joshua X. D. Ang, Luke Alphey, Leen Delang, Clive S. McKimmie and Olga Pleguezuelos

Vaccines 2026, 14(8), 723; https://doi.org/10.3390/vaccines14080723 - 21 Aug 2026

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Abstract

Background/Objectives: Mosquito-borne viruses cause substantial global morbidity and mortality. Mosquito saliva, secreted during biting, facilitates blood feeding and can enhance virus infection. Here, we evaluated whether combining virus-specific antigens with mosquito salivary protein-derived peptides improves protection in Zika virus (ZIKV) and chikungunya [...] Read more.

Background/Objectives: Mosquito-borne viruses cause substantial global morbidity and mortality. Mosquito saliva, secreted during biting, facilitates blood feeding and can enhance virus infection. Here, we evaluated whether combining virus-specific antigens with mosquito salivary protein-derived peptides improves protection in Zika virus (ZIKV) and chikungunya virus (CHIKV) mouse models. Methods: Peptides from Aedes and Culex salivary proteins were selected based on conservation, predicted T-cell reactivity, and cellular and humoral immunogenicity in mice. Mice were immunised subcutaneously with a prime and boost two weeks apart using adjuvanted salivary peptides (SAL), commercial ZIKV- or CHIKV-like particles (VLPs), or salivary peptides combined with the relevant VLPs. Vaccine doses contained 0.5 µg VLPs and/or 10 nmol of each salivary peptide, formulated with Montanide ISA-51; when combined, VLPs and SAL were administered on opposite flanks. Two weeks after boosting, mice were challenged with ZIKV or CHIKV plus Aedes aegypti saliva. Challenge teams were blinded to group allocation until data analyses were complete. Results: SAL enhanced the protective effect of VLP vaccination compared with VLPs alone. In the CHIKV model, CHIKV VLP + SAL prevented joint swelling and reduced infectious virus in the inoculated ankle and viral RNA in the contralateral ankle. In the ZIKV model, ZIKV VLP + SAL reduced viral RNA in skin and brain tissue and improved survival. Conclusions: Mosquito salivary peptide antigens improved the protective efficacy of VLP vaccines against ZIKV and CHIKV in mouse models. Salivary antigens may provide a complementary vaccine component for multiple arboviruses transmitted by Aedes and Culex mosquitoes. Full article

(This article belongs to the Special Issue Arboviral Infections (Dengue, Chikungunya, Zika, and Other Mosquito-Borne Diseases): Immune Response and Vaccine Development)

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11 pages, 296 KB

Open AccessArticle

A Cross-Sectional Seroepidemiological Study on Varicella Zoster Virus in Zhejiang, China

by Yingying Yang, Yan Liu, Canjie Zheng, Yao Zhu, Fuxing Chen, Linling Ding, Yu Hu, Xiaohua Qi and Yang Zhou

Vaccines 2026, 14(8), 722; https://doi.org/10.3390/vaccines14080722 - 21 Aug 2026

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Abstract

Objectives: This study aimed to investigate the levels of varicella antibodies in Zhejiang, China, after a decade of implementing the two-dose varicella vaccine (VarV) strategy. Methods: Healthy participants aged 1 to 69 years from Zhejiang, China, were recruited from January to [...] Read more.

Objectives: This study aimed to investigate the levels of varicella antibodies in Zhejiang, China, after a decade of implementing the two-dose varicella vaccine (VarV) strategy. Methods: Healthy participants aged 1 to 69 years from Zhejiang, China, were recruited from January to April 2024 using multistage stratified random sampling, and varicella zoster virus (VZV) IgG antibodies were detected by ELISA. We assessed the seroprevalence and geometric mean concentration (GMC) of VZV IgG and analyzed related factors using Logistic and linear regression models. Results: A total of 807 participants were included in the study. The overall seropositivity rate for VZV IgG in the healthy population was 73.08% (95%CI: 69.87–76.11), with a corresponding GMC of 200.97 mIU/mL (95%CI: 182.75 mIU/mL–221.01 mIU/mL). Multivariate analysis identified age group, VarV immunization history, and history of varicella disease as factors significantly associated with both VZV IgG seropositivity and GMC levels (p < 0.05). The seropositivity rate for VZV IgG in children aged 1–14 years was 42.67% (95%CI: 36.22–49.31), with a corresponding GMC of 82.10 mIU/mL (95%CI: 69.14 mIU/mL–97.48 mIU/mL). Furthermore, a significant decline in both seropositivity and GMC was observed over time following vaccination among vaccinated children aged 1–14 years (p < 0.05). Conclusions: Two-dose VarV vaccination may be considered for inclusion in the national immunization program. Full article

(This article belongs to the Special Issue Vaccine Preventable Diseases: Surveillance, Coverage, and Immunization Strategy)

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27 pages, 2313 KB

Open AccessReview

Plant-Produced Vaccines for Protection from Human and Veterinary Coronaviruses

by Erin Egelkrout

Vaccines 2026, 14(8), 721; https://doi.org/10.3390/vaccines14080721 - 21 Aug 2026

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Abstract

Coronaviruses are responsible for numerous diseases causing substantial morbidity and mortality to both humans and animals. In particular, they have caused three significant outbreaks in humans including severe acute respiratory syndrome 1 (SARS-CoV-1), Middle East respiratory syndrome (MERS-CoV), and, most recently, the severe [...] Read more.

Coronaviruses are responsible for numerous diseases causing substantial morbidity and mortality to both humans and animals. In particular, they have caused three significant outbreaks in humans including severe acute respiratory syndrome 1 (SARS-CoV-1), Middle East respiratory syndrome (MERS-CoV), and, most recently, the severe acute respiratory syndrome 2 (SARS-CoV-2) pandemic. Two relevant veterinary diseases are porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), which cause severe losses in the pork industry. While efficacious vaccines were developed in an unprecedented timeframe for COVID-19, vaccines have not been commercialized for other human coronaviruses and vaccines against animal coronaviruses have limited efficacy and logistical challenges in administration. There is a clear need for more efficacious vaccines with simpler methods of delivery and administration for both human and veterinary use. The production of subunit vaccines in plant systems holds great promise in addressing the current challenges and facilitate the preparation for future potential outbreaks and new viruses. This review will summarize the state of development of vaccines in plant systems including tobacco, rice, maize, and others. Full article

(This article belongs to the Special Issue Production of Plant-Based Vaccines and Therapeutics)

18 pages, 421 KB

Open AccessArticle

Factors Associated with Prescription-to-Vaccination Conversion and Timeliness: A Real-World Analysis

by Mengru Xiao, Jun Li, Shejun He, Meiqiong Xiang, Xiaohong Dong, Xiaoyang Wang, Xiaoxiao Zhang, Yonghao Guo and Yanyang Zhang

Vaccines 2026, 14(8), 720; https://doi.org/10.3390/vaccines14080720 - 20 Aug 2026

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Abstract

Background: This study evaluated vaccine prescription conversion and identified associated factors in Henan Province, China, during 2025. Methods: The study was conducted in Lingbao City, Henan Province. All vaccine prescriptions issued in 2025 were collected, and vaccination status was linked through the Henan [...] Read more.

Background: This study evaluated vaccine prescription conversion and identified associated factors in Henan Province, China, during 2025. Methods: The study was conducted in Lingbao City, Henan Province. All vaccine prescriptions issued in 2025 were collected, and vaccination status was linked through the Henan Provincial Immunization Information Management System. Subgroup analyses were stratified by vaccine type (NIP vs. non-NIP). Univariate analyses used χ², Mann–Whitney U, and Kruskal–Wallis H tests. Multivariable analyses employed Firth-corrected logistic regression for conversion behavior, and mixed-effects models with random intercepts for patient ID for conversion timeliness, analyzed using a two-part model. All analyses were performed using R software (version 4.5.3). Results: Among 50,887 prescriptions, the overall conversion rate was 13.8%. NIP vaccines had a higher conversion rate than non-NIP vaccines (76.8% vs. 12.5%, p < 0.001) and a higher same-day conversion rate (13.9% vs. 7.4%; χ² = 59.585, p < 0.001), but longer delays among non-same-day conversions (23 vs. 4 days). Manual prescriptions were associated with significantly higher conversion in both NIP (OR = 3.913) and non-NIP (OR = 37.720) subgroups. Vaccination clinics were associated with a nearly 20-fold higher odds (OR = 19.386). Interaction analyses showed manual prescriptions were more strongly associated with conversion and shorter delays in older adults, and had stronger associations with conversion for non-NIP vaccines (χ² = 22.275, p < 0.001). Vaccination clinics were most strongly associated with conversion in children (ΔP = 0.130); however, the improvement in same-day conversion among older adults was relatively smaller, suggesting additional barriers beyond clinic availability may exist in this population. Conclusions: Manual prescriptions and vaccination clinics were associated with higher vaccine prescription conversion, with particularly pronounced effects on non-NIP vaccines. Older adults exhibited the lowest conversion rates. In parallel with promoting electronic prescriptions, co-issuing paper prescriptions is recommended, particularly for non-NIP vaccines and older adults. Full article

(This article belongs to the Special Issue Vaccines and Vaccination Strategies from a Public Health Perspective)

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17 pages, 1244 KB

Open AccessArticle

Beyond Hesitancy: Current Multi-Level Polio Vaccine Refusals and Pathways to Acceptance in a High-Risk Region of Pakistan

by Farhana Tabassum, Maha Azhar, Amal Khalid, Mushtaque Mirani, Narjis Fatima Hussain, Sujeet Lohana, Aadarsh Fateh Muhammad, Khadija Ali and Jai K Das

Vaccines 2026, 14(8), 719; https://doi.org/10.3390/vaccines14080719 - 20 Aug 2026

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Abstract

Background: Pakistan is one of only two countries where wild poliovirus type 1 (WPV1) continues to persist. Vaccine refusals challenge efforts to end the virus, especially in high-risk communities. Methods: A qualitative exploratory study took place from September to November 2025 in three [...] Read more.

Background: Pakistan is one of only two countries where wild poliovirus type 1 (WPV1) continues to persist. Vaccine refusals challenge efforts to end the virus, especially in high-risk communities. Methods: A qualitative exploratory study took place from September to November 2025 in three High-Risk Union Councils (HRUCs) of Karachi, Pakistan. The study examined reasons for refusing the polio vaccine and identified specific communication and operational strategies to improve vaccine acceptance. A total of 23 in-depth interviews and 10 focus group discussions were conducted with 71 participants, including parents who refuse the vaccine, polio program staff, physicians, and government stakeholders. Data were analyzed using a sequential inductive and deductive thematic approach, mapping findings onto the Socio-Ecological Model (SEM) with NVivo 15 (Lumivero, Denver, CO, USA). Results: Factors influencing polio vaccine refusals were interconnected and spanned multiple levels. At the intrapersonal level, campaign fatigue, a lack of knowledge about poliomyelitis, concerns about side effects, and rumors about infertility were common. Community-level factors included household gatekeepers, local influencers, and digital misinformation. Institutional barriers included weak communication from the frontline, inadequate supervision, workforce shortages, poor tracking of refusals, and limited involvement of physicians. At the policy level, refusals were linked to distrust in governance, poor municipal services, and dissatisfaction with vertical campaign methods. Recommended strategies included integrating polio services with routine immunization and primary healthcare, strengthening counseling by physicians, engaging trusted local influencers and community leaders, expanding targeted social media campaigns to counter misinformation, implementing quick responses to rumors, enhancing workforce capacity, and using data-driven microplanning, including targeted SNIDs and focused interventions in areas with chronic refusals. Conclusions: Polio vaccine refusals are shaped by social, communication, operational, and structural factors. Improving communication and operational guidelines by reducing the number of campaigns, increasing active engagement at the frontline, integrating polio activities into routine health services, and addressing misinformation with a dynamic communication strategy may enhance vaccine acceptance and support polio eradication efforts. Full article

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

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22 pages, 5182 KB

Open AccessArticle

Epitope-Based Nipah Virus G and F Head-to-Head Dimer mRNA Vaccines Exhibit Distinct Immunogenicity and Immune Profiles

by Rui Peng, Jiali Xu, Longhai Yuan, Bai Li, Hongyu Chen, Cong Tang, Hao Yang, Yanan Zhou, Yun Yang, Qing Huang, Junbin Wang and Shuaiyao Lu

Vaccines 2026, 14(8), 718; https://doi.org/10.3390/vaccines14080718 - 20 Aug 2026

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Abstract

Background/Objectives: Nipah virus (NiV) is a highly pathogenic zoonotic agent that causes fatal respiratory and neurological diseases, for which no approved vaccines are currently available. To address this unmet need, we developed and evaluated novel mRNA-LNP vaccine candidates. These vaccines employ an epitope- [...] Read more.

Background/Objectives: Nipah virus (NiV) is a highly pathogenic zoonotic agent that causes fatal respiratory and neurological diseases, for which no approved vaccines are currently available. To address this unmet need, we developed and evaluated novel mRNA-LNP vaccine candidates. These vaccines employ an epitope- and structure–guided “immune-focusing” strategy, aiming to maximize the exposure of critical neutralizing epitopes on the viral attachment (G) and fusion (F) glycoproteins. Methods: Head-to-head dimeric antigens (2Gs and 2Fs) were engineered by removing subdominant stalk regions and tandemly duplicating epitope-rich globular head domains. Three LNP-encapsulated candidates-NV1 (encoding 2Gs), NV2 (encoding 2Fs), and NV3 (a 1:1 mixture of NV1 and NV2)-were evaluated in BALB/c mice and Syrian hamsters to systematically assess humoral responses, cytokine secretion, BCR/TCR repertoires, and systemic safety. Results: NV1 and NV3 induced potent binding antibodies and strong neutralizing activity against NiV pseudoviruses. Meanwhile, although NV2 lacked neutralizing activity, it induced superior Th1-biased cellular immunity, accompanied by extensive T-cell clonal proliferation. BCR/TCR sequencing revealed unique adaptive immune characteristics that perfectly align with the distinct immunogenic properties described above. Preliminary safety assessments found no toxicity to vital organs, while active germinal center formation confirmed the success of immune mobilization. Conclusions: An epitope-centered dimer design effectively shapes the unique defense mechanisms of the adaptive immune system. NV3 offers a balanced and synergistic strategy that combines potent humoral and cellular immune defenses, providing a highly promising platform for the development of a Nipah virus (NiV) vaccine. Full article

(This article belongs to the Special Issue Next-Generation Vaccine Platforms for Emerging Infections)

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19 pages, 812 KB

Open AccessArticle

Pfizer Versus Moderna COVID-19 Vaccine Effectiveness Against Mortality: Evidence from Linked Mortality and Vaccination Records in Indiana

by Sadia Farzana, Francesco Maria Rossi, Qian Eric Luo, Jeff Whittle, Kevin McGurk, Benjamin W. Weston, Andy Ye Yuan, Ali Moghtaderi, Vladimir Atanasov and Bernard S. Black

Vaccines 2026, 14(8), 717; https://doi.org/10.3390/vaccines14080717 - 20 Aug 2026

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Abstract

Objective: It is commonly believed in the public health community that the mRNA vaccines from Pfizer and Moderna were broadly similar in preventing COVID-19 mortality, with perhaps a small advantage for Moderna. We revisit this question, using a research design that controls [...] Read more.

Objective: It is commonly believed in the public health community that the mRNA vaccines from Pfizer and Moderna were broadly similar in preventing COVID-19 mortality, with perhaps a small advantage for Moderna. We revisit this question, using a research design that controls for healthy-vaccinee bias. Methods: We studied deaths among persons aged 15 years or greater from January 2021 through December 2022 in Indiana, linked to vaccination records, using an outcome measure, namely COVID-19 Excess Mortality Percentage (CEMP), which uses non-COVID natural mortality to control for HVB. Results: We find both large healthy-vaccinee bias for both vaccines, and larger bias for Pfizervaccinees: Pfizer recipients were healthier and thus would have faced lower COVID-19 mortality without vaccination. For ages 60+, we find almost 50% higher COVID-19 remaining mortality risk (RMR) for Pfizer vaccinees receiving primary vaccination over a “core period” from 2Q2021 through 1Q2022: the average Pfizer/Moderna RMR ratio was 1.49. For ages 15–59, this ratio was 1.25, but was not statistically significant. For booster dose for ages 60+, the average Pfizer/Moderna RMR ratio was 1.34. For 2Q2022 through 4Q2022, after the major Omicron wave, we find much lower vaccine effectiveness and no significant Pfizer–Moderna difference. Conclusions: During the period with both good vaccine availability and high COVID-19 mortality (2Q-2021–1Q2022), the Moderna vaccine was associated with lower COVID-19 mortality, relative to the Pfizer vaccine. A possible explanation is the higher Moderna dose (100 μg vs. 30 for Pfizer). After that period, a high percentage of the population had natural immunity from prior COVID-19 infection; we find only small mortality gains from vaccination, with no significant Pfizer–Moderna difference. Policy Implications: Controlling for healthy-vaccinee bias, Moderna was associated with lower COVID-19 mortality, relative to Pfizer. This difference was not known in real-time due to the failure of the available studies to address healthy-vaccinee bias. Controlling for such bias is vital when making vaccination policy. Full article

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

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34 pages, 4946 KB

Open AccessArticle

Local and Systemic Immune Responses in Growing Feather Pulps and Blood of Broiler Chickens Elicited by Electron Beam- and Formalin-Killed Staphylococcus aureus Vaccines

by Ruvindu Perera, Jossie M. Santamaria, Chrysta N. Beck, Gisela F. Erf, Adnan Alrubaye and Palmy Jesudhasan

Vaccines 2026, 14(8), 716; https://doi.org/10.3390/vaccines14080716 - 20 Aug 2026

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Abstract

Background: Staphylococcus aureus (SA) causes septicemia and arthritis, eventually resulting in substantial economic losses and health hazards in poultry. Lethal electron beam (eBeam) treatment kills bacteria while preserving surface epitopes. Methods: This study compared broiler chicken immune responses (local and systemic) after eBeam-killed [...] Read more.

Background: Staphylococcus aureus (SA) causes septicemia and arthritis, eventually resulting in substantial economic losses and health hazards in poultry. Lethal electron beam (eBeam) treatment kills bacteria while preserving surface epitopes. Methods: This study compared broiler chicken immune responses (local and systemic) after eBeam-killed (eB) or formalin-killed (FK) SA injections. The vaccine (sham) control was endotoxin-free PBS. This study contained six treatments (trt) with five chickens/trt, with vaccine trts divided into two groups, A and B. Group A received in ovo vaccine/sham treatments (phase 1) initially. At 34 d of age, the pulps of growing feathers (GFs) received intradermal (i.d.) injections of the respective trt to elicit booster and primary responses in groups A and B, respectively. Blood was collected to analyze leukocyte populations and plasma SA-specific antibody levels. Additionally, in phase 2, GFs were collected to assess leukocyte presence in GF pulps. Two-way ANOVA was conducted to test the effects of treatment, time, and their interactions, followed by Tukey’s HSD tests at p < 0.05 for statistical significance. Results: Early in phase 1, the eB group had increased SA-specific IgM, IgA, and total lymphocyte concentrations compared with FK. In phase 2, FK and eB i.d. vaccines increased total lymphocyte and T cell proportions in GF pulps compared with sham. In blood, the recall eB vaccination increased monocytes, B cells, CD8+ T cells, and total lymphocytes, while the recall FK vaccination increased heterophils (p < 0.05). Conclusions: Improved early protection at mucosal surfaces may be reflected by higher plasma levels of SA-specific IgM and IgA following in ovo eBeam-killed-SA vaccination. Additionally, both eB-SA and FK-SA vaccines stimulated robust local inflammatory responses dominated by lymphocytes in GF pulps. Full article

(This article belongs to the Special Issue Novel Vaccine Designs to Enhance the Engagement of Innate and Adaptive Immunity)

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24 pages, 7369 KB

Open AccessArticle

Immunoinformatics-Driven Rational Design of Altered Peptide Ligands and In Vitro Validation of a Multi-Epitope CTL Formulation Targeting HPV16 E6/E7

by Dian Dong, Xiuqing Zhang and Bo Li

Vaccines 2026, 14(8), 715; https://doi.org/10.3390/vaccines14080715 - 20 Aug 2026

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Abstract

Background: Therapeutic vaccination against human papillomavirus type 16 (HPV16) is frequently limited by the weak HLA-A*02:01 presentation of native E6/E7 oncoprotein epitopes. This study aims to utilize an integrated computational-experimental pipeline to design and evaluate anchor-optimized altered peptide ligands (APLs) for improving [...] Read more.

Background: Therapeutic vaccination against human papillomavirus type 16 (HPV16) is frequently limited by the weak HLA-A*02:01 presentation of native E6/E7 oncoprotein epitopes. This study aims to utilize an integrated computational-experimental pipeline to design and evaluate anchor-optimized altered peptide ligands (APLs) for improving peptide presentation and HPV16-specific T-cell responses. Methods: Anchor-residue substitutions were introduced into three wild-type E6/E7 epitopes. Candidates were prioritized in silico based on predicted presentation, affinity, immunogenicity, and toxicity, and subsequently evaluated via in vitro functional assays using HLA-A*02:01-positive donor cells and molecular dynamics (MD) simulations. Results: Anchor optimization successfully converted weak binders into strong binders; for instance, E6apl improved predicted affinity from 329.33 to 6.21 nM. Crucially, candidate E7apl1 exhibited normal CD8⁺ T-cell expansion but reduced IFN-γ secretion, revealing a distinct binding–immunogenicity dissociation. MD simulations suggested that altered peptide conformational dynamics may contribute to differences in functional activity. Subsequently, an optimized six-peptide formulation (three APLs and three wild-type epitopes) was assembled. The resulting multi-epitope HPV-specific cytotoxic T lymphocytes (meHPV-CTLs) mediated target-specific cytotoxicity against cervical cancer cells, achieving 74.1% ± 5.1% specific lysis at an effector-to-target ratio of 30:1, which was largely abrogated by HLA class I blockade. Conclusions: These proof-of-concept findings demonstrate that stable peptide–MHC binding is a necessary but insufficient condition for optimal T-cell activation. The experimentally characterized multi-epitope formulation provides a proof-of-concept strategy for further preclinical evaluation of HPV16-targeted peptide-based immunotherapies. Moreover, because these anchor-optimized APLs are defined at the sequence level, these sequence-defined APLs may potentially be explored in alternative vaccine delivery platforms, including mRNA-based approaches, in future studies. Full article

(This article belongs to the Section Human Papillomavirus Vaccines)

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20 pages, 3888 KB

Open AccessArticle

Preclinical Development of ARV-2001, an Intradermally Administered mRNA–Lipid Nanoparticle Immunotherapeutic for the Treatment of HPV-16-Positive Cervical High-Grade Squamous Intraepithelial Lesions

by Zhengxiang He, Huabin Zhu, Ju Hyeong Jeon, Jianzhu Chen, Gregory M. Glenn and Renhuan Xu

Vaccines 2026, 14(8), 714; https://doi.org/10.3390/vaccines14080714 - 19 Aug 2026

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Abstract

Background/Objective: Persistent infection with human papillomavirus type 16 (HPV-16) is the principal cause of cervical high-grade squamous intraepithelial lesions (cHSIL) and cervical cancer, yet the established treatments remain limited to ablative or excisional procedures that carry reproductive risk and do not eliminate the [...] Read more.

Background/Objective: Persistent infection with human papillomavirus type 16 (HPV-16) is the principal cause of cervical high-grade squamous intraepithelial lesions (cHSIL) and cervical cancer, yet the established treatments remain limited to ablative or excisional procedures that carry reproductive risk and do not eliminate the underlying infection. We report the preclinical development of ARV-2001, a messenger RNA (mRNA)–lipid nanoparticle (LNP) immunotherapeutic encoding mutated, non-oncogenic HPV-16 E6 and E7 fused to a SARS-CoV-2 spike S2 subdomain enriched in human CD4 helper epitopes, formulated in a novel cholesterol-derived ionizable lipid (ARV-T1). Methods: Interactions of ARV-2001-expressed antigens with p53 and retinoblastoma (Rb) were evaluated in human cervical carcinoma cell line C33A, in lentiviral constructs in primary human keratinocytes, and in soft-agar colony-formation assays. ARV-2001 was administrated by intramuscular (IM) or intradermal (ID) injection in naive mice or in the TC-1 tumor models. Tumor size and survival were monitored over time and tumor-infiltrated lymphocytes were characterized by flow cytometry. Intracellular cytokine staining and Elispot were used to evaluate immunogenicity. Results: In vitro, the mutated E6/E7–S2 antigen lost the ability to degrade p53, to deregulate the retinoblastoma (Rb) pathway, and to support anchorage-independent growth, suggesting abrogation of oncogenic activity. The S2 domain and imiquimod administration each augmented antitumor activity and intratumoral CD8⁺ T-cell infiltration while reducing myeloid-derived suppressor cells in the syngeneic HPV-16 E6/E7 TC-1 tumor models. In addition, ID administration of ARV-2001 into TC-1 tumor-bearing mice was superior to IM administration in terms of both tumor growth inhibition and survival. ID vaccination with ARV-2001 in mice consistently elicited a more potent E6/E7-specific T-cell response than the same dose given IM. Dose-escalation studies showed a dose-dependent T cell response against E6/E7 in ID-injected mice. Conclusions: This study supports future human evaluation of intradermally administrated ARV-2001 for treatment of HPV-16+ cHSIL in clinical trials. Full article

(This article belongs to the Section Human Papillomavirus Vaccines)

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21 pages, 828 KB

Open AccessArticle

Cost-Effectiveness Analysis of Older Adult Vaccination with the Bivalent Respiratory Syncytial Virus Prefusion F (RSVpreF) Vaccine in Mexico

by Veronica Guajardo, Ali Shajarizadeh, Nishu Gaind, Luka Ivkovic, Rengina Kefalogianni and Diana Mendes

Vaccines 2026, 14(8), 713; https://doi.org/10.3390/vaccines14080713 - 19 Aug 2026

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Abstract

Background/Objectives: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults, and in Mexico’s rapidly growing older-adult population it may place increasing pressure on hospital-based care; however, Mexico-specific evidence to inform adult RSV immunization policy remains limited. This study estimated the [...] Read more.

Background/Objectives: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults, and in Mexico’s rapidly growing older-adult population it may place increasing pressure on hospital-based care; however, Mexico-specific evidence to inform adult RSV immunization policy remains limited. This study estimated the long-term clinical and economic burden of medically attended RSV among adults aged 60–99 years in Mexico and evaluated the health impact and cost-effectiveness of a year-round RSVpreF vaccination program. Methods: A population-based Markov cohort model compared the RSVpreF vaccination with no vaccination in a hypothetical Mexican cohort aged 60–99 years over a lifetime horizon. Outcomes included RSV-related hospitalizations, emergency department (ED) and physician office (PO) encounters, in-hospital deaths, life-years (LYs), and quality-adjusted life-years (QALYs). Analyses were conducted from Mexican healthcare system and societal perspectives in 2025 Mexican pesos (MXN$) and US dollars (US$), with costs and outcomes discounted at 5% annually. One-way and probabilistic sensitivity analyses and scenario analyses assessed the robustness of the findings. Results: With 58% uptake, RSVpreF reduced hospitalizations by 187,825, ED encounters by 178,278, PO encounters by 465,976, and RSV-related deaths by 15,384. In the first 5 years, hospitalizations, ED encounters, and deaths declined by 31% each, and PO encounters by 14%. Over the lifetime horizon, vaccination generated an additional 96,227 discounted LYs and 71,526 discounted QALYs, while avoiding MXN$ 19,484 million (US$ 1061 million) in direct medical costs and MXN$ 3324 million (US$ 181 million) in indirect costs. Conclusions: Year-round RSVpreF vaccination in Mexico among adults aged 60–99 years could substantially reduce medically attended RSV cases and RSV-related mortality and is projected to be cost-effective, thereby supporting the adoption of preventive strategies to address the growing clinical and economic burden of RSV in Mexico’s aging population. Full article

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

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17 pages, 1528 KB

Open AccessArticle

Patterns and Predictors of Influenza Vaccination Uptake Among Healthcare Personnel in Kuwait: A Nationwide Multi-Season Study

by Saleh Alsarhan, Fatema Alkhulaifi and Lolwah Alzafiri

Vaccines 2026, 14(8), 712; https://doi.org/10.3390/vaccines14080712 - 19 Aug 2026

Viewed by 351

Abstract

Background/Objectives: Healthcare personnel (HP) are a priority group for seasonal influenza vaccination due to their increased occupational exposure and potential to transmit influenza in healthcare settings. This study examined patterns and factors associated with in-season influenza vaccination uptake among HP in Kuwait. [...] Read more.

Background/Objectives: Healthcare personnel (HP) are a priority group for seasonal influenza vaccination due to their increased occupational exposure and potential to transmit influenza in healthcare settings. This study examined patterns and factors associated with in-season influenza vaccination uptake among HP in Kuwait. Methods: A nationwide observational study was conducted using Ministry of Health (MOH) administrative records covering the 2022/2023 through 2024/2025 influenza seasons. A person–season dataset was constructed, comprising one observation per HP for each of the three seasons. The primary outcome was in-season influenza vaccination, defined as receipt of an influenza vaccine between September and March of a given study season. Independent variables included age, sex, nationality, governorate of residence, profession, managerial position, previous-year influenza vaccination status, and pre-season sickness absence duration (days). Generalized estimating equations (GEE) logistic regression model with an exchangeable correlation structure was used to estimate factors associated with vaccination uptake. Results: The final analytic dataset included 48,886 HP contributing 146,658 person–season observations across three influenza seasons. Overall, in-season vaccination uptake was 8.7%, and repeated vaccination across seasons was uncommon. Older age, male sex, non-Kuwaiti nationality, and being a physician were independently associated with higher odds of in-season influenza vaccination. Previous-year influenza vaccination was the strongest predictor of current-season vaccination uptake (aOR 2.01, 95% CI 1.87–2.16; p < 0.001). Compared with HP with no pre-season sickness absence, those with 1–3 pre-season sickness absence days had slightly higher adjusted odds of vaccination (aOR 1.08, 95% CI 1.03–1.14), whereas those with ≥8 days had lower adjusted odds (aOR 0.91, 95% CI 0.85–0.97). Conclusions: In-season influenza vaccination uptake among HP in Kuwait was low across three consecutive influenza seasons, with limited continuity of annual vaccination. Previous-year vaccination was the strongest predictor of current-season vaccination uptake, while the association between pre-season sickness absence and vaccination varied by absence duration. These findings support continued efforts to improve and sustain in-season influenza vaccination uptake among HP, while further research is needed to clarify the factors underlying vaccination decisions. Full article

(This article belongs to the Section Influenza Virus Vaccines)

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14 pages, 3083 KB

Open AccessArticle

Influenza Vaccine Effectiveness Against Pneumonia and COPD Exacerbations Among Patients with Chronic Obstructive Pulmonary Disease in Thailand: A National Test-Negative Design Study, 2013–2024

by Sutthinan Chawalchitiporn, Pichaya Tantiyavarong, Jiraphut Kittiwatanachod, Suriya Naosri, Kriengkrai Prasert and Prabda Praphasiri

Vaccines 2026, 14(8), 711; https://doi.org/10.3390/vaccines14080711 - 18 Aug 2026

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Abstract

Background/Objectives: Influenza infection is a major trigger of pneumonia and acute exacerbations among patients with chronic obstructive pulmonary disease (COPD). However, national laboratory-confirmed evidence on influenza vaccine effectiveness (VE) in this high-risk population remains limited. This study aimed to estimate the effectiveness of [...] Read more.

Background/Objectives: Influenza infection is a major trigger of pneumonia and acute exacerbations among patients with chronic obstructive pulmonary disease (COPD). However, national laboratory-confirmed evidence on influenza vaccine effectiveness (VE) in this high-risk population remains limited. This study aimed to estimate the effectiveness of seasonal influenza vaccination against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand. Methods: We conducted a nationwide retrospective test-negative design study using administrative healthcare data from the National Health Security Office linked with laboratory-confirmed influenza surveillance data between 1 June 2013 and 31 May 2025, covering twelve influenza seasons (2013–2024). COPD-related clinical episodes among patients aged ≥40 years who presented with pneumonia or acute exacerbation of COPD and underwent RT-PCR testing for influenza were included. Modified Poisson regression with cluster-robust standard errors was used to estimate adjusted risk ratios (RRs), and VE was calculated as (1 − adjusted RR) × 100. Results: A total of 606,072 COPD-related clinical episodes were included, of which 192,224 (31.7%) were influenza-positive. The overall adjusted VE against influenza-associated pneumonia was 55.9% (95% CI: 47.3–63.1), while VE against influenza-associated COPD exacerbations was 67.0% (95% CI: 48.8–78.8). VE estimates were broadly similar across age groups and consistent across COPD severity strata. Conclusions: Seasonal influenza vaccination was associated with substantial protection against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand. Full article

(This article belongs to the Section Influenza Virus Vaccines)

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19 pages, 5758 KB

Open AccessArticle

A CHO-Expressed Pseudorabies Virus gD Subunit Vaccine Elicits Potent Neutralizing Antibodies and Confers Complete Protection Against Lethal Challenge in Mice

by Caoyuan Ma, Jia Li, Xin Song, Tao Wang, Qiang Yang, Ruojia Huang, Mengxiang Cao, Shengmei Chen, Yongfeng Li, Yuzi Luo, Yimin Wang, Lian-Feng Li, Hua-Ji Qiu, Hongxia Wu and Yuan Sun

Vaccines 2026, 14(8), 710; https://doi.org/10.3390/vaccines14080710 - 18 Aug 2026

Viewed by 383

Abstract

Background/Objectives: Pseudorabies virus (PRV) variant strains have caused widespread outbreaks in China since 2011, and currently available vaccines provide suboptimal protection. Glycoprotein D (gD), the principal target of virus-neutralizing antibodies, represents a promising antigen for subunit vaccine development. However, CHO cell-based production [...] Read more.

Background/Objectives: Pseudorabies virus (PRV) variant strains have caused widespread outbreaks in China since 2011, and currently available vaccines provide suboptimal protection. Glycoprotein D (gD), the principal target of virus-neutralizing antibodies, represents a promising antigen for subunit vaccine development. However, CHO cell-based production systems suitable for large-scale manufacturing remain insufficiently explored. This study aimed to develop a potentially scalable CHO cell-derived PRV gD subunit vaccine and evaluate its immunogenicity and protective efficacy in mice. Methods: A stable Chinese hamster ovary (CHO) suspension cell line secreting the extracellular domain of PRV gD was established through signal peptide optimization and stepwise serum-free adaptation. The recombinant gD protein was purified using Ni²⁺- Sepharose High-Performance affinity chromatography and subsequently formulated with MONTANIDE ISA 206 adjuvant. Immunogenicity and protective efficacy were assessed in BALB/c mice through serological analysis, neutralization assays, lethal challenge experiments, and quantitative PCR. Results: The gD subunit vaccine induced rapid seroconversion of gD-specific IgG antibodies as early as 7 days post immunization and exhibited a strong booster effect, maintaining high antibody levels. Neutralizing antibodies were first detected at 14 days and increased significantly after booster immunization, with titers markedly exceeding those induced by a commercial inactivated PRV vaccine at 42 days (p = 0.001). Following lethal challenge with 10⁴ TCID₅₀ of the highly virulent PRV-TJ variant strain, vaccinated mice achieved 100% survival without clinical signs. Viral genome copy numbers in the brain and spinal cord were reduced by approximately 3.3 to 4.4 log₁₀ relative to the PBS control group. Conclusions: The CHO cell-derived PRV gD subunit vaccine elicits robust humoral immune responses and provides complete protection against lethal PRV variant challenge in mice. These findings support its further evaluation in the natural swine host toward the development of a safe and scalable subunit vaccine for pseudorabies control. Full article

(This article belongs to the Special Issue Infectious Diseases and Immunization in Animals)

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10 pages, 725 KB

Open AccessPerspective

mRNA-1010 and the Future of Seasonal Influenza Prevention: Towards Next-Generation Respiratory Vaccination

by Antonios-Periklis Panagiotopoulos, Deny Tsakri, Kyriaki Ranellou, Cleo Anastassopoulou and Athanasios Tsakris

Vaccines 2026, 14(8), 709; https://doi.org/10.3390/vaccines14080709 - 18 Aug 2026

Viewed by 685

Abstract

Seasonal influenza remains a major global public health challenge despite decades of vaccine development, underscoring the need for more effective and adaptable immunization strategies. The recently approved mRNA-1010 vaccine represents a promising advance by applying messenger RNA technology to a pathogen characterized by [...] Read more.

Seasonal influenza remains a major global public health challenge despite decades of vaccine development, underscoring the need for more effective and adaptable immunization strategies. The recently approved mRNA-1010 vaccine represents a promising advance by applying messenger RNA technology to a pathogen characterized by continuous antigenic drift. Recent Phase 3 clinical trials conducted in support of regulatory review have demonstrated robust immunogenicity and superior protective efficacy against seasonal influenza compared with standard influenza vaccines in adults aged 50 years and older. However, increased reactogenicity, particularly among younger adults, together with the need for continued post-marketing safety surveillance, highlights the balance between enhanced immune responses and tolerability. Beyond seasonal influenza, mRNA-1010 provides a foundation for next-generation respiratory vaccines, including combination formulations targeting influenza, SARS-CoV-2, and respiratory syncytial virus (RSV), while illustrating the broader potential of mRNA vaccine technology. At the same time, challenges related to manufacturing scalability, cost, cold-chain requirements, and global accessibility remain important considerations for widespread implementation. This perspective examines whether mRNA-1010 represents an incremental advance in influenza vaccination or a potential transformative milestone in respiratory immunization, while considering the continuing roles of alternative vaccine platforms in achieving optimal effectiveness, safety, and equitable global access. Full article

(This article belongs to the Special Issue Developing Recombinant Vaccines and Immunotherapy Strategies for Emerging Viral Diseases)

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18 pages, 2416 KB

Open AccessArticle

Safety and Immunogenicity of SW-BIC-213, a Modified COVID-19 Lipo-Polyplex mRNA Vaccine, in Laotian Healthy Adults Aged 18 Years and Above: A Phase 1/2 Trial

by Ying Yuan, Yichao Zeng, Mingxiong Zhu, Ziyu Sun, Weiwei Xu, Yinran Hu, Guanzhou Liu, Mingyun Shen, Chen Yang and Di Gao

Vaccines 2026, 14(8), 708; https://doi.org/10.3390/vaccines14080708 - 18 Aug 2026

Viewed by 345

Abstract

Background/Objectives: Messenger RNA vaccines can induce strong immune responses, but delivery, biodistribution, and storage stability remain important considerations. We evaluated the safety and immunogenicity of SW-BIC-213, a Lipo-Polyplex (LPP)-based mRNA vaccine against SARS-CoV-2, in healthy adults in Laos. Methods: We conducted a seamless [...] Read more.

Background/Objectives: Messenger RNA vaccines can induce strong immune responses, but delivery, biodistribution, and storage stability remain important considerations. We evaluated the safety and immunogenicity of SW-BIC-213, a Lipo-Polyplex (LPP)-based mRNA vaccine against SARS-CoV-2, in healthy adults in Laos. Methods: We conducted a seamless phase 1/2 clinical trial in healthy adults. Phase 1 enrolled adults aged 18–60 years in an open-label, single-arm dose-escalation study; phase 2 enrolled adults aged ≥18 years in a randomized, double-blind, placebo-controlled study. Participants received two doses 21 days apart. The primary endpoints were safety in phase 1 and safety and immunogenicity in phase 2. Results: In phase 1, 41 participants received 25 or 45 μg of SW-BIC-213. In phase 2, 480 participants were randomized in a 2:2:1 ratio to receive 25 μg, 45 μg, or placebo. All phase 1 adverse reactions were grade 1 or 2; grade 3 reactions in phase 2 were limited to transient fever. At 14 days after the second dose, pseudovirus neutralizing-antibody seroconversion exceeded 99% against wild-type virus, 98% against Delta, 84% against Omicron BA.1, and 88% against BA.2. Neutralizing-antibody titers were higher in both vaccine groups than in the placebo group (p < 0.0001). Conclusions: Two doses of SW-BIC-213 showed an acceptable safety profile and substantial humoral immunogenicity in healthy adults aged ≥18 years. Full article

(This article belongs to the Special Issue Epidemiology, Vaccines and Surveillance of COVID-19)

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13 pages, 5046 KB

Open AccessArticle

An Outer Membrane Vesicle-Based Vaccine Combined with alb-Flt3L Promotes Durable Antitumor Immunity in HPV-Associated Cancer

by Yining Liu, Yichu Xu, Yu-Cheng Chang, Ya-Chea Tsai, Tzyy-Choou Wu and Chien-Fu Hung

Vaccines 2026, 14(8), 707; https://doi.org/10.3390/vaccines14080707 - 18 Aug 2026

Viewed by 329

Abstract

Background/Objectives: Human papillomavirus (HPV)-associated cancers remain a major global health burden, and no therapeutic cancer vaccine has yet been approved. Oncoprotein E7 plays a key role in tumor initiation and progression and has been identified as a potential target. Here, we aim [...] Read more.

Background/Objectives: Human papillomavirus (HPV)-associated cancers remain a major global health burden, and no therapeutic cancer vaccine has yet been approved. Oncoprotein E7 plays a key role in tumor initiation and progression and has been identified as a potential target. Here, we aim to improve the efficacy and durability of an outer membrane vesicle (OMV)-based E7-targeted vaccine, SOMV-9RE7, through alb-Flt3L combination therapy. Methods: The antitumor efficacy and durability of the combination therapy were evaluated in low-burden and high-burden HPV-positive TC-1 tumor-bearing mouse models. Systemic and local immune responses were investigated by flow cytometry. Results: Combination with alb-Flt3L improved the tumor control and prolonged the therapeutic durability of SOMV-9RE7 compared with monotherapy groups, with more than half of the treated mice surviving beyond 60 days. This combination strategy enhanced E7-specific CD8⁺ T cell immunity in peripheral blood and the spleen, reduced myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, promoted splenic T cell memory formation, and reshaped the tumor microenvironment. Conclusions: Combining vaccine SOMV-9RE7 with alb-Flt3L improves antitumor efficacy and durability. This therapeutic benefit is associated with both systemic and local immune remodeling, supporting the combination therapy as a promising strategy for therapeutic cancer vaccines. Full article

(This article belongs to the Section Human Papillomavirus Vaccines)

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18 pages, 781 KB

Open AccessSystematic Review

Comparator-Dependent Safety Signals for Incident Systemic Autoimmune Rheumatic Diseases After mRNA COVID-19 Vaccination: A Systematic Review

by Larisa Pinte, Paul Balanescu, Alina Dima, Ana-Maria Mandescu, Mirela-Emanuela Simion-Stanciu, Andra-Cristiana Dumitru and Cristian Baicus

Vaccines 2026, 14(8), 706; https://doi.org/10.3390/vaccines14080706 - 17 Aug 2026

Viewed by 435

Abstract

Background: Pharmacovigilance systems have flagged possible associations between mRNA COVID-19 vaccination and systemic autoimmune inflammatory rheumatic diseases (AIRDs), generating uncertainty for rheumatologists counselling patients. As the first population-scale deployment of an mRNA vaccine platform, COVID-19 vaccination provides a unique setting to examine whether [...] Read more.

Background: Pharmacovigilance systems have flagged possible associations between mRNA COVID-19 vaccination and systemic autoimmune inflammatory rheumatic diseases (AIRDs), generating uncertainty for rheumatologists counselling patients. As the first population-scale deployment of an mRNA vaccine platform, COVID-19 vaccination provides a unique setting to examine whether autoimmune safety signals detected in spontaneous reporting systems correspond to measurable disease risk. We synthesised pharmacovigilance and population-based evidence on incident EULAR-defined systemic AIRDs after mRNA COVID-19 vaccination and assessed whether disproportionality signals were corroborated by analytical studies. Methods: We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, Web of Science, Scopus, Embase, and the Cochrane Library from 2019 to April 2026, supplemented by medRxiv and trial registries. Eligible studies included pharmacovigilance disproportionality analyses and analytical studies, including cohorts and randomised controlled trials, evaluating BNT162b2 or mRNA-1273 in adults without known pre-existing autoimmune disease. Risk of bias was assessed using READUS-PV, ROBINS-I, and RoB 2. Meta-analysis was not performed because of substantial heterogeneity. Results: Fourteen studies were included: seven pharmacovigilance studies and seven analytical studies. Disproportionality analyses suggested increased reporting of selected AIRDs, most consistently polymyalgia rheumatica and giant cell arteritis, mainly when all other adverse-event reports served as comparators. These signals were largely neutral when influenza vaccines were the reference. Across analytical studies, associations were inconsistent; modest increases in systemic lupus erythematosus appeared only in selected analyses. Long-term evidence was scarce: only four studies, from three countries (South Korea, Israel, and Norway), followed participants for up to approximately one year, and three of these reported at least one positive association—systemic lupus erythematosus, post-booster rheumatoid arthritis, and polymyalgia rheumatica in older adults—whereas studies restricted to risk windows of three months or less reported no increase. Conclusions: The available evidence does not indicate a consistent increase in incident systemic AIRDs after mRNA COVID-19 vaccination. Although pharmacovigilance studies identified comparator-dependent signals for selected diseases, particularly polymyalgia rheumatica and giant cell arteritis, these findings were generally not confirmed in comparative population-based studies and should be considered hypothesis-generating. Delayed-onset disease remains poorly characterised, and studies with at least one year of follow-up are needed. Full article

(This article belongs to the Special Issue Safety and Side Effects in SARS-CoV-2 Vaccine)

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25 pages, 2418 KB

Open AccessSystematic Review

Determinants of the Seasonal Influenza Vaccination Uptake Among People Aged 50 Years or Above During and After the Pandemic: A Systematic Review

by Liwen Ding, Siyu Chen, Fuk-yuen Yu, Ka Hei Chan, Yuan Fang, Phoenix K. H. Mo and Zixin Wang

Vaccines 2026, 14(8), 705; https://doi.org/10.3390/vaccines14080705 - 15 Aug 2026

Viewed by 406

Abstract

Background/Objectives: Seasonal influenza vaccination (SIV) coverage remains suboptimal among adults aged ≥50 years, and the COVID-19 pandemic might influence the determinants of SIV uptake. This systematic review aimed to identify determinants of SIV uptake among adults aged ≥50 years during and after the [...] Read more.

Background/Objectives: Seasonal influenza vaccination (SIV) coverage remains suboptimal among adults aged ≥50 years, and the COVID-19 pandemic might influence the determinants of SIV uptake. This systematic review aimed to identify determinants of SIV uptake among adults aged ≥50 years during and after the COVID-19 pandemic. Methods: We searched PubMed, MEDLINE, Embase, Web of Science, Global Health, CINAHL, Cochrane Library, APA PsycINFO, and APA PsycArticles for studies published between 1 December 2019 and 1 January 2026. The pooled prevalence of SIV uptake was synthesized using random-effects models in meta-analysis. Results: A total of 50 studies were included in the systematic review. COVID-19-related factors, such as perceived risk of co-infection with SARS-CoV-2 and seasonal influenza and concerns about potential interactions between COVID-19 vaccines and SIV, were determinants of SIV uptake. Other modifiable determinants included those that existed before the pandemic (e.g., knowledge and perceptions of seasonal influenza and SIV). Subgroup analysis showed that cost and inaccessibility were barriers to receiving SIV in places without a fully subsidized SIV, and perceived susceptibility and vaccine safety concerns were commonly identified as facilitators and barriers in studies with data collected after the pandemic. The pooled prevalence of SIV uptake among adults aged 50 years or above was 53% (95% confidence interval: 44–62%). Such uptake appeared lower among adults aged 50–64 years, in regions without a fully subsidized SIV, and after the COVID-19 pandemic. Conclusions: These findings could inform service planning and interventions promoting SIV uptake among adults aged ≥50 years in the post-pandemic era. More studies are needed to explore determinants specific to people aged 50–64 years to inform health promotion tailored to their needs. Full article

(This article belongs to the Special Issue Global Immunization Inequities-Challenges and Solutions)

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10 pages, 215 KB

Open AccessArticle

Assessment of Immunization Levels in Children with Chronic Diseases in a Tertiary Hospital

by Murat Ersoy and Betül Ulukol

Vaccines 2026, 14(8), 704; https://doi.org/10.3390/vaccines14080704 - 14 Aug 2026

Viewed by 283

Abstract

Background/Objective: Vaccination is one of the most effective and cost-effective preventive health measures for preventing infectious diseases. The literature reports that children with chronic illnesses have lower vaccination rates than healthy children and are at higher risk for preventable diseases. This study aimed [...] Read more.

Background/Objective: Vaccination is one of the most effective and cost-effective preventive health measures for preventing infectious diseases. The literature reports that children with chronic illnesses have lower vaccination rates than healthy children and are at higher risk for preventable diseases. This study aimed to determine the immunization status of children with chronic illnesses, assess vaccination rates, and help raise awareness on this issue. Material/Method: Children aged 1 month to 18 years who presented to or were admitted to the Pediatric Clinic of Mersin City Education and Research Hospital between 1 March and 30 June 2024, and who were followed up for their chronic illness, and whose parents gave their consent, were included in the study. Sociodemographic data and information about routine and vaccines outside the national immunization schedule (Rotavirus, meningococcal, HPV, Influenza) were obtained from the parents. The status of vaccination of disease-specific recommended vaccines was also recorded. Results: A total of 256 children were included in the study (mean age 8.7 ± 4.69 years; 42.2% girls). A high rate of complete vaccination according to the routine vaccination schedule was observed. However, non-routine vaccinations were administered at low rates: rotavirus 9%, meningococcal 4.7%, and influenza 12.2%. The HPV vaccine was administered to only one patient in the study group. Recommended vaccines for the disease were administered to only 16.4% of eligible children. Conclusions: Children with chronic illnesses are at high risk for infection and complications. Increasing vaccine awareness among both healthcare professionals and parents will contribute to higher immunization rates. Comprehensive studies are needed to identify factors influencing vaccination in this population. Full article

(This article belongs to the Special Issue Vaccine Epidemiology and Population Health)

14 pages, 1120 KB

Open AccessArticle

The Epidemiological and Economic Burden of Vaccine-Preventable Respiratory Diseases Among Adults Aged 65 Years and Older in the Nordic Countries

by Nicoline Weinreich Reinstrup, Renée Hangaard Gidsel, Terho Heikkinen, Anne Margarita Dyrhol-Riise, Lars-Åke Levin, Lars Jørgen Østergaard and Lars Holger Ehlers

Vaccines 2026, 14(8), 703; https://doi.org/10.3390/vaccines14080703 - 13 Aug 2026

Viewed by 432

Abstract

Background: Despite the increasing availability of tailored vaccines, vaccine-preventable respiratory diseases (VPRDs), including influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease (PD), continue to impose a significant health and economic burden. This study assessed the epidemiological and economic burden of VPRD [...] Read more.

Background: Despite the increasing availability of tailored vaccines, vaccine-preventable respiratory diseases (VPRDs), including influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease (PD), continue to impose a significant health and economic burden. This study assessed the epidemiological and economic burden of VPRD among adults aged ≥65 across four Nordic countries (Denmark, Sweden, Norway, and Finland). Methods: Data on incidence, hospital admissions, and mortality were obtained from national statistics (week 21, 2024–week 20, 2025) and supplemented with peer-reviewed literature. A static model was developed to quantify epidemiological and economic burden associated with VPRD during the 2024/2025 winter season. Results: During the 2024/2025 season, VPRD resulted in approximately 830,000 symptomatic cases, 60,300 hospital admissions, and 7750 deaths across the Nordic countries. COVID-19 showed the highest estimated incidence and numbers of hospital admissions, followed by influenza, PD, and RSV. Mortality was comparable between COVID-19 and influenza, followed by PD and RSV. Annual healthcare costs were approximately €1132 million, with productivity losses constituting an additional 7%. Conclusions: Despite national vaccination efforts, VPRDs remain a major health and economic burden in the Nordic countries. Strengthening immunization programs through improved vaccine uptake, broader coverage, and use of advanced vaccines may contribute to further reducing this burden. Full article

(This article belongs to the Section Epidemiology and Vaccination)

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26 pages, 2441 KB

Open AccessReview

The Vaccine–Field Strain Gap in Bovine Neonatal Diarrhea: Molecular Epidemiology of Rotavirus, Coronavirus, and Enterotoxigenic Escherichia coli and Priorities for Vaccine Updating

by Gyeong-Seo Park, Minsung Park, Somin Lee, Chonghan Kim and Byoung Joo Seo

Vaccines 2026, 14(8), 702; https://doi.org/10.3390/vaccines14080702 - 13 Aug 2026

Viewed by 293

Abstract

Bovine neonatal diarrhea (BND) is a leading cause of morbidity and mortality in pre-weaned calves. Commercial maternal vaccines targeting bovine rotavirus (BRV), bovine coronavirus (BCoV), and enterotoxigenic Escherichia coli (ETEC) have been available for decades, yet field outbreaks continue in vaccinated herds. This [...] Read more.

Bovine neonatal diarrhea (BND) is a leading cause of morbidity and mortality in pre-weaned calves. Commercial maternal vaccines targeting bovine rotavirus (BRV), bovine coronavirus (BCoV), and enterotoxigenic Escherichia coli (ETEC) have been available for decades, yet field outbreaks continue in vaccinated herds. This review examined peer-reviewed literature published between January 2019 and March 2026, identified through a structured PubMed search supplemented by reference-list screening. For BRV, a field strain sharing its VP7 genotype with a vaccine component was not neutralized by vaccine-induced antiserum, indicating that genotype concordance does not predict serologic coverage. For BCoV, hemagglutinin-esterase variation and regional lineage divergence indicate surface-protein evolution, although data linking these changes to reduced efficacy are not available. For ETEC, adhesin diversity and antimicrobial resistance affect both vaccination strategy and case management. Maternal vaccination retains biological value, but field performance is constrained by colostral variability, incomplete passive transfer, and product-to-product immunogenic differences. For all three pathogens, antigenic divergence from vaccine strains is located at individual epitopes, receptor-binding domains, or adhesins rather than at the level of whole-pathogen identity. Subunit and multi-epitope antigen designs, for which proof-of-concept constructs have been reported, operate at this level, and their selection requires characterization of candidate antigens for efficacy, diversity, polymorphism, and cross-protective breadth. Such antigen improvements address the pathogen-side gap but not the passive-transfer and mucosal constraints. Functional surveillance to guide antigen updating, field trials that measure passive-transfer efficiency, and adjunctive strategies are identified as priorities for BND control. Full article

(This article belongs to the Section Veterinary Vaccines)

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34 pages, 30184 KB

Open AccessArticle

An In Vitro Screen Identifies H1 Influenza Hemagglutinin Substitutions That Alter mRNA-LNP Vaccine Responses Against the Stalk Domain

by Samuel W. Rovito, Po-Ling Chen, Guohua Yang, Haley N. Writt, Ashley N. Zalla, Marissa A. Donofrio, Jonathan N. Fogo, Richard J. Webby, James D. Brien and Charles J. Russell

Vaccines 2026, 14(8), 701; https://doi.org/10.3390/vaccines14080701 - 13 Aug 2026

Viewed by 407

Abstract

Background: Conformational stability has been shown to modulate the immunogenicity of structural class 1 viral fusion glycoproteins, yet the relationship between influenza A hemagglutinin (HA) stability and antigenicity remains poorly understood. Methods: Here, we screened a panel of 21 A/Hawaii/70/2019 (H1N1) HA mutants [...] Read more.

Background: Conformational stability has been shown to modulate the immunogenicity of structural class 1 viral fusion glycoproteins, yet the relationship between influenza A hemagglutinin (HA) stability and antigenicity remains poorly understood. Methods: Here, we screened a panel of 21 A/Hawaii/70/2019 (H1N1) HA mutants for expression, cleavage, and acid and conformational stability in cells. Twelve mutant HA proteins expressed from transfected plasmid constructs that showed relatively robust expression compared to WT also exhibited either altered stability or glycosylation deletion. mRNA-LNPs were generated containing these 12 HAs, along with the wild-type (WT) HA, to investigate the mutational effects on mRNA-LNP vaccine immunogenicity and protection in mice. Hemagglutination inhibition, microneutralization, and total serum IgG ELISAs were performed using a panel of H1N1 antigens to evaluate humoral immune responses at 28 days post vaccination. The vaccinated mice were then subjected to lethal challenge with a forward-drifted H1N1 virus. Results: Most mutant HA candidates elicited WT-like serological responses and provided protection against challenge, although noticeable decreases in serological responses and, to a lesser extent, protection were observed, especially among G72K- and R109E-vaccinated mice. Of note, substitutions at position E107 enhanced total IgG responses against the HA stalk. Modest, but detectable, increases in antibody-dependent cellular cytotoxicity (ADCC) were also observed, particularly with E107R. Although substitution-specific differences in weight loss were found in E107-vaccinated mice challenged with a mouse-adapted Cal/09 virus, these differences were minor, and protection against the forward-drifted challenge virus and a heterologous PR8 challenge virus was no different from that in mice vaccinated with WT HA. Conclusions: These findings demonstrate the ability of specific substitutions to alter components of humoral immunity by shifting HA domain-specific antibody responses, which could prove useful in the design and development of HA vaccine antigens possessing optimized immunogenicity. Full article

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

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22 pages, 1385 KB

Open AccessArticle

Application of Vaccination Behavioural Models Based on Modified Proxy Measures for C Scales and Characteristics of Their Determinants in Patients Vaccinated Against Infectious Diseases: A Cross-Sectional Survey

by Tomasz Hikawczuk, Dorota Stefanicka-Wojtas, Agnieszka Rusiecka, Maria Kasprzyk-Smardz, Monika Zadka, Norbert Zachara, Jarosław Zachara, Stanisław Karol Manulik, Katarzyna Lomper, Izabella Uchmanowicz and Donata Kurpas

Vaccines 2026, 14(8), 700; https://doi.org/10.3390/vaccines14080700 - 13 Aug 2026

Viewed by 244

Abstract

Background: C scales are important measures that can support the vaccination process by analysing the possible reasons for vaccination hesitancy. In some studies, it is not possible to utilise typical models based on the traditional 3C–7C scales, but it is possible to [...] Read more.

Background: C scales are important measures that can support the vaccination process by analysing the possible reasons for vaccination hesitancy. In some studies, it is not possible to utilise typical models based on the traditional 3C–7C scales, but it is possible to adjust them by using modified proxy measures and converting individual determinants into variables of similar significance in the logistic regression analysis of a vaccination behavioural model. Objective: The aim of this study was to compare the relationship between determinants defining a vaccination behaviour model based on the classic 3C, 5C, and 7C scales with modified proxy measures and two variables (low vaccine-related fear instead of complacency and exposure to misinformation-prone digital sources instead of conspiracy) and the dependent variable, namely, the vaccination status of patients of primary care centres in Poland from 2024 to 2025. Methods: A cross-sectional study was conducted using a survey and questionnaire data linked with patient records from three Polish health centres (N = 1206, 46.9% rural residents and 53.1% city residents). Demographic data and determinants of three vaccination behaviour models were compared between vaccinated and non-vaccinated patients using Pearson’s χ² test, while behavioural models based on the 3C, 5C, and 7C scales describing the relationship between independent variables and vaccination status (dependent variable) were prepared using logistic regression. Two of seven determinants were changed. Results: All determinants used in the three logistic regression behavioural models differed significantly between vaccinated and non-vaccinated patients (p < 0.001). Furthermore, independent variables in each behavioural model were significantly related to the dependent variable (p < 0.001). With an increasing number of model determinants, Nagelkerke’s R² increased from 0.303 to 0.435 and the ROC-AUC from 0.828 to 0.882. However, the VIF value indicated very low multicollinearity of determinants. The Wald test did not reveal a significant relationship between confidence in public health and the dependent variable (p > 0.05, OR 1.17–0.92 for Models 1 and 3, respectively). Conclusions: In the vaccination behavioural models prepared based on empirical data, all determinants were found to be significantly related to the dependent variable. As the number of independent variables in the behavioural model increased, parameters such as the ROC-AUC and Nagelkerke’s R² also increased, while the Akaike information criterion, which determines the balance between fitting the model to data and its complexity, decreased. No significant individual relationship was found for the determinant “confidence in public health”, but this result confirms observations from other previous studies describing the impact of pandemic fatigue, misinformation, and conflicting expert information on institutional trust. Full article

(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 3rd Edition)

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9 pages, 1146 KB

Open AccessCommunication

Intradermal Vaccination Induces Protective Immunity Against Foot-and-Mouth Disease While Mitigating Milk Yield Reduction in Ruminants

by Dong-Wan Kim, Seo-Yong Lee, So Eon Kim, Tae-Jun Kim, Hyejin Kim, Ji-Hyeon Hwang, Sun Young Park, Young-Joon Ko, Yoon-Hee Lee, Jong-Hyeon Park and Sung-Han Park

Vaccines 2026, 14(8), 699; https://doi.org/10.3390/vaccines14080699 - 13 Aug 2026

Viewed by 315

Abstract

Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease causing substantial economic losses in livestock. Conventional intramuscular (IM) vaccination is widely used for FMD control but may be associated with transient reductions in milk production. This study evaluated whether intradermal (ID) vaccination [...] Read more.

Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease causing substantial economic losses in livestock. Conventional intramuscular (IM) vaccination is widely used for FMD control but may be associated with transient reductions in milk production. This study evaluated whether intradermal (ID) vaccination could induce comparable immune responses and protection while minimizing potential impacts on productivity. Methods: In cattle, the immunogenicity of an experimental bivalent ID vaccine was compared with that of a commercially available IM vaccine by measuring antibody responses for up to 140 days post-vaccination (dpv). Milk production was monitored for 7 dpv in a separate cohort of lactating cattle. Protective efficacy was evaluated in goats following ID vaccination and challenge with a 2025 Republic of Korea serotype O field isolate (O/ME-SA/Ind-2001). Results: ID vaccination induced humoral immune responses comparable to those elicited by IM vaccination throughout the 140-day observation period. Although no statistically significant difference in milk production was observed, the ID group showed a smaller numerical reduction in milk yield. Following viral challenge, ID-vaccinated goats developed rapid neutralizing antibody responses, exhibited no clinical signs, and showed lower viral RNA levels than unvaccinated controls. Conclusions: Intradermal vaccination induced long-lasting immune responses comparable to conventional IM vaccination, was associated with a smaller numerical reduction in milk yield, and protected goats against challenge with a contemporary FMDV field isolate. These findings provide preliminary evidence supporting the potential of ID vaccination as an alternative strategy for FMD control in ruminants and warrant further comparative studies with conventional IM vaccination. Full article

(This article belongs to the Section Veterinary Vaccines)

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12 pages, 233 KB

Open AccessPerspective

Lessons Unlearned: The Barriers to Lyme Borreliosis Vaccination and the Risk of Repeating History

by Deepak Nagra, Kathryn Biddle, Katie Bechman, Victoria Allen and James Galloway

Vaccines 2026, 14(8), 698; https://doi.org/10.3390/vaccines14080698 - 12 Aug 2026

Viewed by 488

Abstract

Lyme borreliosis is the most common vector-borne disease in the temperate Northern Hemisphere, with approximately 476,000 diagnoses annually in the United States and over 130,000 reported cases across Europe each year, figures that substantially underestimate true incidence. In 1998, LYMErix became the first [...] Read more.

Lyme borreliosis is the most common vector-borne disease in the temperate Northern Hemisphere, with approximately 476,000 diagnoses annually in the United States and over 130,000 reported cases across Europe each year, figures that substantially underestimate true incidence. In 1998, LYMErix became the first licensed vaccine against Lyme borreliosis. Its withdrawal four years later was not driven by evidence of vaccine failure but by the collapse of public confidence, and regulatory endorsement that any successful vaccine programme requires. The field was without a licensed product for twenty-four years. VLA15 (now designated PF-07307405), a second-generation recombinant outer surface protein A vaccine, is now at regulatory submission following phase 3 results reported in March 2026. We examine the barriers that led to LYMErix’s withdrawal, revisit the evidence that generated and sustained the safety controversy and consider whether the conditions now exist for a different outcome. The lessons for a robust post-marketing surveillance programme extend beyond Lyme borreliosis to broader questions about how modern medicine evaluates vaccine risk, interprets safety signals, and communicates under uncertainty. Full article

33 pages, 18363 KB

Open AccessArticle

Comparative Evaluation of Plant-Derived Virus-like Particles as Intratumoral Immunotherapy Agents

by Anete Ogrina-Komarova, Zane Kalnina, Rebeka Racina, Vilija Zeltina, Ramona Petrovska, Ina Balke, Patricija Zaremba, Krista Resne, Juris Jansons and Andris Zeltins

Vaccines 2026, 14(8), 697; https://doi.org/10.3390/vaccines14080697 - 12 Aug 2026

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Abstract

Background: Plant-derived virus-like particles (VLPs) are emerging nanoplatforms for local cancer immunotherapy, yet their relative performance across structurally distinct particles remains insufficiently defined. Methods: We performed a comparative benchmarking study of eleven plant-derived VLPs spanning diverse architectures and functional properties using an integrated [...] Read more.

Background: Plant-derived virus-like particles (VLPs) are emerging nanoplatforms for local cancer immunotherapy, yet their relative performance across structurally distinct particles remains insufficiently defined. Methods: We performed a comparative benchmarking study of eleven plant-derived VLPs spanning diverse architectures and functional properties using an integrated workflow of physicochemical characterization, immune-functional profiling, and in vivo evaluation. All VLPs were produced in endotoxin-minimized ClearColi BL21 (DE3), enabling assessment of intrinsic particle-associated immunostimulatory activity with reduced bacterial endotoxin confounding. Results: In vitro, several VLPs stimulated macrophage-associated responses and enhanced tumor cell killing, although classical M1/M2 polarization markers in RAW264.7 cells did not consistently predict functional cytotoxicity. In a subset of candidates, HEK-TLR3 reporter activity varied substantially under RNA-normalized conditions and was not predicted solely by total RNA content or apparent RNA size distribution. Five candidates were advanced to intratumoral evaluation in the male-derived B16-F10 melanoma model, where CCMV-ss and CMVtt showed trends toward reduced tumor progression and increased immune cell infiltration in male mice. Furthermore, host sex-associated differences in baseline immune features were observed, though these must be interpreted with caution given the H-Y antigen-driven immunogenicity inherent to the male-derived B16-F10 model in female hosts. Conclusions: This study establishes a standardized comparative framework linking plant VLP properties with immune-functional performance and identifies CCMV-ss and CMVtt as promising candidates for further development as locally administered cancer immunotherapy nanoplatforms. Full article

(This article belongs to the Special Issue Next-Generation Platforms for Vaccine Design and Immune Evaluation)

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22 pages, 293 KB

Open AccessArticle

Parental Acceptance of Nirsevimab for RSV Prevention in Infants Across Two Consecutive Seasons in Emilia-Romagna, Italy

by Susanna Esposito, Valentina Fainardi, Maria Elena Capra, Melodie O. Aricò, Angela Lanzoni, Francesco Accomando, Gaia Giorgia Arnesano, Cosimo Neglia, Enrico Valletta, Giacomo Biasucci and Serafina Perrone

Vaccines 2026, 14(8), 696; https://doi.org/10.3390/vaccines14080696 - 12 Aug 2026

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Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab, a long-acting monoclonal antibody, provides single-dose protection during the RSV season, but the effectiveness of prophylaxis programs depends on sustained parental acceptance and [...] Read more.

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab, a long-acting monoclonal antibody, provides single-dose protection during the RSV season, but the effectiveness of prophylaxis programs depends on sustained parental acceptance and high uptake. This study evaluated changes in parental knowledge, perceptions, and willingness to accept nirsevimab across two consecutive RSV seasons in Emilia-Romagna, Italy. Methods: Two multicenter cross-sectional surveys were conducted during consecutive RSV seasons, 2024–2025 and 2025–2026, using a comparable questionnaire and recruitment approach. Parents or legal guardians of infants eligible for nirsevimab completed a semi-structured questionnaire during routine counseling in neonatal units. Survey 1 included 1042 respondents and survey 2 included 867 respondents. Sociodemographic characteristics, RSV awareness, knowledge and perception of nirsevimab, willingness to accept prophylaxis, trust in healthcare providers and the healthcare system, preferred information sources, and willingness to pay were compared between seasons. Results: Willingness to administer nirsevimab remained high and stable—87.04% in survey 1 and 88.00% in survey 2. Awareness of RSV-related risks increased from 68.23% to 73.47% (p < 0.05), and correct identification of nirsevimab as an antibody increased from 65.93% to 71.74% (p < 0.01). Explicit refusal rose slightly from 2.21% to 3.81% (p < 0.05). In survey 2, acceptance was associated with higher education, awareness of RSV risks, perceived child susceptibility, confidence in efficacy, lower concern about side effects, trust in pediatricians and the healthcare system, and willingness to pay. Notably, acceptance in 2025–2026 was higher among infants born in September–December than among those born in January–March, indicating a late-season decline. Conclusions: Parental acceptance of nirsevimab remained high across two seasons. Future campaigns should address residual knowledge gaps, reinforce communication on safety and efficacy, and sustain high coverage throughout the entire RSV season, particularly among infants born in its final months. Full article

(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 3rd Edition)

26 pages, 2763 KB

Open AccessArticle

Integrated Field Evaluation of a Caseous Lymphadenitis Vaccine and Environmental Bacteriological Profiling in Commercial Goat Farms in South Korea

by Gyeong-Seo Park, Somin Lee, Minsung Park, Minseok Kim, Eunhui Lee, Sungmin Lee, Myung Hyee Kim, Byeong Yeal Jung, Chonghan Kim and Byoung Joo Seo

Vaccines 2026, 14(8), 695; https://doi.org/10.3390/vaccines14080695 - 12 Aug 2026

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Abstract

Background/Objectives: Caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis, is difficult to control on goat farms because of subclinical infection, abscess rupture, environmental contamination, and repeated herd-level exposure. This study evaluated a Korean inactivated CLA vaccine under commercial goat farm conditions and [...] Read more.

Background/Objectives: Caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis, is difficult to control on goat farms because of subclinical infection, abscess rupture, environmental contamination, and repeated herd-level exposure. This study evaluated a Korean inactivated CLA vaccine under commercial goat farm conditions and combined vaccination outcomes with farm-level bacteriological profiling. Methods: Goats from three commercial farms were allocated according to baseline CLA serostatus and vaccination status into seropositive vaccinated, seronegative vaccinated, seropositive non-vaccinated, and seronegative non-vaccinated control groups. Vaccinated goats received two intramuscular doses at weeks 0 and 4. Clinical signs, external abscess occurrence, growth performance, CLA-specific antibody responses, and abscess bacterial loads were monitored. Farm-level microbial profiles were assessed using culture, MALDI-TOF MS, and targeted PCR. Results: Baseline antibody classification showed strong agreement between the commercial CLA ELISA and the in-house whole-bacterial IgG ELISA, with a Spearman’s rho of 0.89 (p < 0.001) and 96.7% classification agreement. Vaccination induced CLA-specific antibody responses in both assays and was not associated with a persistent reduction in growth performance. External abscesses were observed only in baseline seropositive goats. Abscesses occurred in 1/30 vaccinated and 2/15 non-vaccinated seropositive goats, but the difference was not statistically significant (p = 0.254). Microbial profiling showed farm-dependent detection patterns. Conclusions: The vaccine induced CLA-specific antibody responses (immunogenicity) with acceptable tolerability. The exploratory abscess endpoint was underpowered, and clinical protection was not confirmed; larger studies are needed. Full article

(This article belongs to the Section Veterinary Vaccines)

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20 pages, 3571 KB

Open AccessArticle

Impact of Preweaning Vaccination on Host Gene Expression Patterns Linked to Future Bovine Respiratory Disease Development in Beef Calves

by Hudson R. McAllister, Bradly I. Ramirez, Sarah F. Capik, Kelsey M. Harvey, Paul S. Morley, Robert J. Valeris-Chacin, Brandi B. Karisch, Amelia R. Woolums, Alexis C. Thompson and Matthew A. Scott

Vaccines 2026, 14(8), 694; https://doi.org/10.3390/vaccines14080694 - 12 Aug 2026

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Abstract

Background/Objectives: Bovine respiratory disease (BRD) remains a major concern in cattle research, and the long-term effects of vaccination on health and immune responses are not well defined. This study compared gene expression in vaccinated (VAX) and unvaccinated (NOVAX) preweaned calves and subsequent BRD [...] Read more.

Background/Objectives: Bovine respiratory disease (BRD) remains a major concern in cattle research, and the long-term effects of vaccination on health and immune responses are not well defined. This study compared gene expression in vaccinated (VAX) and unvaccinated (NOVAX) preweaned calves and subsequent BRD development during backgrounding. Methods: Whole blood was collected at four timepoints (TIME; T1-4; median age 107, 114, 183, and 230, respectively) from 73 bull calves enrolled in a blinded randomized controlled trial; VAX calves received a commercial attenuated multivalent viral vaccine at T1 and T3. Results: Whole-blood transcriptomics was used to quantify mRNA, identifying 5364 differentially expressed genes (DEGs) for TIME, 84 DEGs for vaccination (VAX), and 129 for BRD status using both glmmSeq and QLF testing (glmmSeq only DEGs: 11,068 TIME, 358 VAX, and 9241 BRD). VAX calves at T3 were clustered uniquely with the enrichment of pathways related to the cellular response to stress, neutrophil degranulation, and antigen processing and presentation compared to NOVAX cattle and VAX at other timepoints. Interferon pathways, natural killer cell responses, and neutrophil activity were generally absent across all timepoints, while antigen presentation pathways were persistently enriched. Regardless of vaccination or future BRD diagnosis, immunological development over time was indicated by DEGs related to adaptive immunity, lymphocyte development, and inflammatory resolution. At T4, cattle diagnosed with BRD during backgrounding had differential gene expression related to oxygen transport, hemoglobin function, and metabolic processes compared to cattle that remained healthy. Conclusions: This study provides insights into the possible genomic mechanisms underlying vaccine responses and preclinical BRD susceptibility in preweaned beef cattle. Full article

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

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Vaccines, Volume 14, Issue 8 (August 2026) – 77 articles

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