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Vaccines, Volume 13, Issue 5 (May 2025) – 96 articles

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15 pages, 2145 KiB  
Article
Single-Dose Intranasal Immunization with ChAd68-Vectored Prefusion F Vaccines Confers Sustained Protection Against Respiratory Syncytial Virus in Murine Models
by Jing Miao, Xuejie Li, Yingwen Li, Lingjing Mao, Wenkai Suo and Jiaming Lan
Vaccines 2025, 13(5), 528; https://doi.org/10.3390/vaccines13050528 - 15 May 2025
Abstract
Background/Objectives: Respiratory syncytial virus (RSV) poses a substantial global health threat, particularly impacting infants and vulnerable pediatric populations through severe respiratory morbidity. Methods: We developed a novel adenoviral vector vaccine platform utilizing chimpanzee adenovirus 68 (AdC68) to deliver prefusion F (pre-F) antigens from [...] Read more.
Background/Objectives: Respiratory syncytial virus (RSV) poses a substantial global health threat, particularly impacting infants and vulnerable pediatric populations through severe respiratory morbidity. Methods: We developed a novel adenoviral vector vaccine platform utilizing chimpanzee adenovirus 68 (AdC68) to deliver prefusion F (pre-F) antigens from RSV subtypes A and B, generating three vaccine candidates: AdC68-A (subtype A), AdC68-B (subtype B), and AdC68-A+B (bivalent formulation). Results: Single intranasal (i.n.) immunization and prime–boost immunizations via intramuscular (i.m.) routes in BALB/c mice induced robust immune activation, with single i.n. administration conferring durable protection evidenced by an 85% reduction in pulmonary viral loads (p < 0.05) at 134 days post-immunization. All vaccine formulations via i.n. single administration elicited potent subtype-specific IgG responses (geometric mean titers 50–12,800) and Th1-polarized cellular immunity (552–1201 IFN-γ+ spot-forming units/106 PBMCs, IgG2a/IgG1 > 1) in bivalent formulation group, while i.m. boosting enhanced cellular responses 3-fold versus prime immunization alone (p < 0.01). Notably, despite undetectable serum-neutralizing antibodies and absent mucosal IgA in bronchoalveolar lavage at 7 days post-i.n. immunization, the sustained viral control highlights non-neutralizing antibody-mediated protective mechanisms. Conclusions: These findings establish the proof-of-concept for adenoviral-vectored intranasal vaccines against RSV, though optimization of humoral response induction and mucosal immunity duration require further investigation. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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12 pages, 977 KiB  
Article
Is Brazil Reversing the Decline in Childhood Immunization Coverage in the Post-COVID-19 Era? An Interrupted Time Series Analysis
by Ramon Costa Saavedra, Rita Carvalho-Sauer, Enny S. Paixao, Maria Yury Travassos Ichihara, Maria da Conceição Nascimento Costa and Maria da Glória Teixeira
Vaccines 2025, 13(5), 527; https://doi.org/10.3390/vaccines13050527 - 15 May 2025
Abstract
Background: The COVID-19 pandemic had significant impacts on healthcare systems, including the disruption of essential services such as childhood immunization. Containment measures, such as social distancing, contributed to reduced adherence to vaccination programs, increasing the risk of re-emerging vaccine-preventable diseases. We aim [...] Read more.
Background: The COVID-19 pandemic had significant impacts on healthcare systems, including the disruption of essential services such as childhood immunization. Containment measures, such as social distancing, contributed to reduced adherence to vaccination programs, increasing the risk of re-emerging vaccine-preventable diseases. We aim to assess the evolution of childhood vaccination coverage in Brazil from 2010 to 2024, identifying trends before, during, and after the COVID-19 pandemic. Methods: An interrupted time series (ITS) study was conducted using publicly available aggregated data on vaccination coverage for children under one year of age. Prais–Winsten regression models were applied to estimate trend changes and evaluate the impact of the pandemic on immunization levels. Results: The findings indicate a progressive decline in vaccination coverage between 2010 and 2019, which was intensified in 2020 by the pandemic. The BCG vaccine showed the greatest decline (−24.88%, p < 0.001), while pentavalent and hepatitis B vaccines decreased annually by −3.72% and −2.21%, respectively. From 2021 onwards, a gradual recovery in coverage was observed, with significant increases for BCG (+7.48% per year, p < 0.001), hepatitis B (+7.45%, p = 0.014), and MMR (+6.73%, p = 0.017) vaccines. Discussion: The results highlight a concerning decline in childhood immunization, exacerbated by the pandemic but showing recent signs of recovery. This scenario underscores structural challenges within the National Immunization Program, requiring coordinated efforts to reverse vaccination losses and ensure system resilience in the face of future crises. Full article
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20 pages, 290 KiB  
Review
Helicobacter pylori Vaccine: Mechanism of Pathogenesis, Immune Evasion and Analysis of Vaccine Types
by Jingwen Gong, Qing Wang, Xing Chen and Junhui Lu
Vaccines 2025, 13(5), 526; https://doi.org/10.3390/vaccines13050526 - 15 May 2025
Abstract
Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that colonizes the human gastric mucosa, leading to various gastric diseases. H. pylori infection has become a pressing public health issue that affects more than 50% of the human population worldwide, almost 40 years [...] Read more.
Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that colonizes the human gastric mucosa, leading to various gastric diseases. H. pylori infection has become a pressing public health issue that affects more than 50% of the human population worldwide, almost 40 years after its discovery. Traditional treatments, based on the use of bismuth-based triple and quadruple therapies, are effective while facing a series of problems, such as difficulty in patient compliance, the rise of antibiotic resistance, and possible recurrence of infection. Therefore, the development of an efficacious vaccine against H. pylori would be extremely urgent. This review mainly elaborates on the pathogenic mechanism and immune evasion mechanism of H. pylori, as well as various strategies adopted in vaccine development, including whole-cell vaccines, subunit vaccines, DNA vaccines, and live vector vaccines. Animal studies and clinical trials demonstrate that H. pylori vaccines significantly reduce bacterial load and provide cellular immunity over some time. Multiple studies have clarified the advantages and limitations of each candidate vaccine. Although the development of H. pylori vaccines provides benefits to reduce the global burden, there are still significant challenges to developing vaccines in safety, efficacy, and availability. Overcoming these challenges, along with the advancement of vaccine technology, can better prevent and treat H. pylori infection. Full article
(This article belongs to the Section Clinical Immunology)
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11 pages, 2051 KiB  
Article
Identification and Validation of Th1-Selective Epitopes Derived from Proteins Overexpressed in Breast Cancer Stem Cells
by Denise L. Cecil, Daniel Herendeen, Meredith Slota, Megan M. O’Meara, Yushe Dang, Lauren Corulli and Mary L. Disis
Vaccines 2025, 13(5), 525; https://doi.org/10.3390/vaccines13050525 - 15 May 2025
Abstract
Background: Breast cancer stem cells (CSCs), particularly those enriched in triple-negative breast cancer (TNBC), are key contributors to tumor recurrence, metastasis, and resistance to therapy. CSCs often undergo epithelial-to-mesenchymal transformation (EMT), enhancing their invasiveness. Immune-based strategies that selectively target CSC/EMT antigens offer a [...] Read more.
Background: Breast cancer stem cells (CSCs), particularly those enriched in triple-negative breast cancer (TNBC), are key contributors to tumor recurrence, metastasis, and resistance to therapy. CSCs often undergo epithelial-to-mesenchymal transformation (EMT), enhancing their invasiveness. Immune-based strategies that selectively target CSC/EMT antigens offer a promising therapeutic approach. Methods: Twelve candidate CSC/EMT-associated proteins were identified through a systematic literature review. Human serum samples were assessed for antigen-specific IgG using ELISA. Th1/Th2 cytokine profiles, in response to predicted MHC II epitopes, were measured by ELISPOT in PBMCs. Epitope immunogenicity and tumor inhibition were evaluated in murine models, using either TNBC or luminal B syngeneic breast cancer cell lines. Results: Six of the candidate proteins (SOX2, YB1, FOXQ1, MDM2, CDH3, CD105) elicited antigen-specific IgG in human serum. Th1-selective epitopes, defined by high Th1/Th2 ratios, were identified for five of these proteins. Immunization of mice with peptide pools derived from CD105, CDH3, MDM2, SOX2, and YB1 induced significant antigen-specific IFN-γ responses. Tumor growth was significantly inhibited in the vaccinated mice across both the TNBC and luminal B breast cancer models, with mean tumor volume reductions ranging from 61% to 70%. Conclusions: CSC/EMT-associated antigens are immunogenic in humans and can be targeted using Th1-selective epitope-based vaccines. Immunization with these epitopes effectively inhibits tumor growth in multiple murine models of breast cancer. These findings support further clinical evaluation of CSC/EMT-targeted vaccines, especially for high-risk or advanced-stage breast cancer patients. Full article
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20 pages, 986 KiB  
Review
Past, Present, and Future of Viral Vector Vaccine Platforms: A Comprehensive Review
by Justin Tang, Md Al Amin and Jian L. Campian
Vaccines 2025, 13(5), 524; https://doi.org/10.3390/vaccines13050524 - 15 May 2025
Abstract
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often [...] Read more.
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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18 pages, 4923 KiB  
Article
A Computationally Designed Prefusion Stabilized Human Metapneumovirus Fusion Protein Vaccine Antigen Elicited a Potent Neutralization Response
by Michael Kishko, Antonia Stuebler, Sukanya Sasmal, Yvonne Chan, Dean Huang, Christopher Reyes, Jasmine Lin, Owen Price, Ana Kume, Katie Zong, Christine Bricault, Judith Alamares-Sapuay and Linong Zhang
Vaccines 2025, 13(5), 523; https://doi.org/10.3390/vaccines13050523 - 15 May 2025
Abstract
Background/Objectives: Human metapneumovirus (hMPV) is a leading cause of respiratory infections in the elderly, with high morbidity and mortality and with no vaccines or specific therapies available. The primary protective antigen of hMPV is the fusion protein, and its prefusion conformation (pre-F) is [...] Read more.
Background/Objectives: Human metapneumovirus (hMPV) is a leading cause of respiratory infections in the elderly, with high morbidity and mortality and with no vaccines or specific therapies available. The primary protective antigen of hMPV is the fusion protein, and its prefusion conformation (pre-F) is considered the most promising target for vaccine development. Methods: Utilizing computational design strategies focused on intraprotomer interface stabilization, we designed hMPV pre-F recombinant subunit vaccine candidates based on the most prevalent A2 subtype and characterized them in vitro and in vivo, benchmarking to the prototypical hMPV pre-F stabilized by an introduction of a proline at site 185. Results: The top candidate (N46V_T160F) yielded 14.4 mg/L with a melting temperature of 79.3 °C as compared to 5.7 mg/L and 70.4 °C for the benchmark. By employing monoclonal antibody binding to all six antigenic sites of hMPV pre-F, we confirmed this construct retained all pre-F specific antigenic sites and that the key sites Ø and V were stable at 4 °C for up to 6 months. When immunogenicity of N46V_T160F was evaluated in mice, it induced higher binding and neutralizing antibody titers than the benchmark, which stemmed in part from increased levels of site Ø and site II targeting Abs. Further, this A2 based construct induced cross-neutralizing Abs against all four hMPV subtypes. Lastly, our construct exhibited similar immunogenicity as the recently published next-generation hMPV pre-F constructs, DS-CavEs2 and v3B_Δ12_D454C-V458C. Conclusions: N46V_T160F is a promising hMPV vaccine candidate paving the way for further development and optimization. Full article
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14 pages, 920 KiB  
Review
Is Influenza Vaccination Our Best ‘Shot’ at Preventing MACE? Review of Current Evidence, Underlying Mechanisms, and Future Directions
by Alexia El Khoury, Joy Abou Farah and Elie Saade
Vaccines 2025, 13(5), 522; https://doi.org/10.3390/vaccines13050522 - 14 May 2025
Abstract
Background: Major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death, are the leading contributors to global morbidity and mortality worldwide. Accumulating evidence suggests a strong association between influenza infection and increased risk of MACE, especially in high-risk populations. Influenza vaccination [...] Read more.
Background: Major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death, are the leading contributors to global morbidity and mortality worldwide. Accumulating evidence suggests a strong association between influenza infection and increased risk of MACE, especially in high-risk populations. Influenza vaccination has been proposed as a potential strategy for reducing this risk by mitigating systemic inflammation and preventing atherosclerotic plaque destabilization, although the precise mechanisms remain under investigation. Results: Multiple meta-analyses and RCTs suggest that influenza vaccination is associated with a reduced risk of MACE, particularly in high-risk individuals with preexisting cardiovascular disease, but the results are less consistent for primary prevention in low-risk populations. The current data support the importance of early and annual vaccination for optimizing cardiovascular outcomes. Conclusions: Influenza vaccination is emerging as an effective and accessible strategy to reduce the risk of major adverse cardiovascular events, particularly in high-risk individuals. While further research is needed to clarify its role in low-risk populations and the underlying mechanisms of protection, current evidence supports its integration into cardiovascular preventive care. Full article
(This article belongs to the Special Issue Vaccines and Vaccine Preventable Diseases)
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20 pages, 1791 KiB  
Review
Clinical and Fundamental Research Progressions on Tumor-Infiltrating Lymphocytes Therapy in Cancer
by Jiandong Hu, Mengli Jin, Weihong Feng, Barbara Nassif-Rausseo, Alexandre Reuben, Chunhua Ma, Gregory Lizee and Fenge Li
Vaccines 2025, 13(5), 521; https://doi.org/10.3390/vaccines13050521 - 14 May 2025
Abstract
Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy—encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy—has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form [...] Read more.
Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy—encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy—has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form of treatment elicits substantial antigen-specific immune responses, enhances or restores anti-tumor immunity, thereby facilitating the control and destruction of tumor cells, and yielding durable responses across a range of cancers, which can lead to the eradication of tumor lesions and the prevention of recurrence. Tumor-infiltrating lymphocytes (TILs), a subset of ACT, are characterized by their heterogeneity and are found within tumor tissues, where they play a crucial role in mediating host antigen-specific immune responses against tumors. This review aims to explore recent advancements in the understanding of TILs biology, their prognostic implications, and their predictive value in therapeutic contexts. Full article
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13 pages, 1177 KiB  
Article
Differences in Mpox and Vaccinia Immunity Induced by Non-Replicating and Replicating Vaccinia-Based Vaccines
by Getahun Abate, Krystal Meza, Yinyi Yu, Chase Colbert, Anna Jaunarajs, Azra Blazevic, Daniel F. Hoft and Sharon E. Frey
Vaccines 2025, 13(5), 520; https://doi.org/10.3390/vaccines13050520 - 14 May 2025
Abstract
Background: The recent global outbreak with clade IIb and the concurrent emergence of clade I mpox virus in Africa show that mpox is a challenging problem. MVA-BN induces low-level mpox-neutralizing antibody responses that wane rapidly. This study was conducted to compare the [...] Read more.
Background: The recent global outbreak with clade IIb and the concurrent emergence of clade I mpox virus in Africa show that mpox is a challenging problem. MVA-BN induces low-level mpox-neutralizing antibody responses that wane rapidly. This study was conducted to compare the mpox immunity induced by a replication-competent smallpox vaccine and non-replicating MVA-BN. Methods: Stored sera (n = 302) and PBMCs (n = 244) collected pre-vaccination and at five post-vaccination time points in MVA-BN and six post-vaccination time points in Dryvax clinical trials were used. Antibody titers that neutralized at least 50% of mpox in cell culture were determined by the focus reduction neutralization test (FRNT) 50, and the mpox-specific T cell responses were measured using an IFN-γ ELISPOT assay. Results: The peak geometric fold rise (95% CI) (i.e., the maximum GMFR across all study visits) in the mpox FRNT50 for subcutaneous (SC) MVA-BN, intradermal (ID) MVA-BN, and Dryvax was 22.1 (8.3, 59.1), 18.5 (8.0, 43.1), and 245.8 (100.4, 601.6), respectively. The GMFR at day 180 post-vaccination for MVA-BN (SC), MVA-BN (ID), and Dryvax was 2.4, 2.7, and 64, respectively. The mean (95% CI) peak number of mpox-specific IFN-γ-producing SFCs was 127 (43.1, 238.3), 87.3 (46, 137), and 61.2 (44.3, 77.7) for MVA-BN (SC), MVA-BN (ID), and Dryvax, respectively. On day 180, the mean SFCs in the three groups decreased to 10.8 (−34.4, 3.8), 3.3 (−6.2, 18.6), and 2.2 (−9, 12.5), respectively. Conclusions: The peak mpox-neutralizing antibody titer was >10-fold lower in MVA-BN recipients compared to those who received a replication-competent smallpox vaccine, and the level at day 180 was >20 times lower in MVA-BN recipients. MVA-BN induced similar or higher T cell responses. Full article
(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)
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21 pages, 2225 KiB  
Article
Allocation of Oral Cholera Vaccines in Africa
by Elisa M. Maffioli and Yutong Lu
Vaccines 2025, 13(5), 519; https://doi.org/10.3390/vaccines13050519 - 14 May 2025
Abstract
Objectives: In this study, we examine the allocation of oral cholera vaccines (OCVs) across 25 African countries between 2013 and 2019. Methods: We constructed a dataset combining cholera outbreaks and requests, decisions, and deliveries of OCVs from the Global Task Force on Cholera [...] Read more.
Objectives: In this study, we examine the allocation of oral cholera vaccines (OCVs) across 25 African countries between 2013 and 2019. Methods: We constructed a dataset combining cholera outbreaks and requests, decisions, and deliveries of OCVs from the Global Task Force on Cholera Control, alongside additional covariates. Using machine learning algorithms, we assess the relative importance of socio-demographic, governance, and weather variables in predicting cholera outbreaks. We constructed and used an “index of cholera risk” as an instrumental variable to predict the likelihood of suspected cases and estimate the impact of cholera outbreaks on OCV allocation. Results: The majority of OCVs (77.4%) were allocated reactively. Governments took an average of 299.6 days to request doses, international agencies took 10.4 days to decide, and it took 84 days for vaccines to be delivered. Countries experiencing a cholera outbreak were 31.7 and 36.5 percentage points more likely to request and receive a vaccine delivery in the same month as the outbreak, respectively. We confirmed that the probability of obtaining vaccines through a reactive mechanism was 48.4 percentage points higher compared to preventive allocation. When exploring the heterogeneity of impacts, OCVs were more likely to be requested, allocated, and delivered in countries with strong institutions and those not facing crisis situations. OCVs were also more likely to be allocated in the central parts of the continent. Conclusions: While OCV allocation is responsive to cholera outbreaks, addressing delays, particularly in high-risk countries, could improve their distribution and mitigate the impact of cholera outbreaks. This study highlights the need for targeted strategies to ensure vaccine access in fragile and conflict-affected settings, where institutional capacity is weaker. Full article
(This article belongs to the Section Human Vaccines and Public Health)
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14 pages, 867 KiB  
Brief Report
Serological Correlate of Protection Established by Neutralizing Antibodies Differs Among Dialysis Patients with SARS-CoV-2 Variants of Concern
by Guy Rostoker, Stéphanie Rouanet, Myriam Merzoug, Hiba Chakaroun, Mireille Griuncelli, Christelle Loridon, Ghada Boulahia and Luc Gagnon
Vaccines 2025, 13(5), 518; https://doi.org/10.3390/vaccines13050518 - 13 May 2025
Abstract
Background: The 2019 coronavirus disease (COVID-19) pandemic had a severe impact on frail, end-stage kidney disease (ESKD) patients, either on dialysis or transplanted, with a high mortality rate in the early waves. Vaccination against SARS-CoV-2 with mRNA vaccines has led to reduced hospitalization [...] Read more.
Background: The 2019 coronavirus disease (COVID-19) pandemic had a severe impact on frail, end-stage kidney disease (ESKD) patients, either on dialysis or transplanted, with a high mortality rate in the early waves. Vaccination against SARS-CoV-2 with mRNA vaccines has led to reduced hospitalization and mortality rates in the general population and ESKD patients. Neutralizing antibodies (NAbs) are a valuable correlate of protection after vaccination, and IgG anti-spike antibodies are considered a surrogate marker of protection. Methods: This study investigated the correlates of protection brought by NAb and anti-spike IgG antibodies against SARS-CoV-2 wild-type Wuhan strain and variants of concern in a cohort of 128 French patients on dialysis after vaccination with the BNT162b2 mRNA vaccine. The correlate was assessed using Receiver Operating Characteristic curves. Results: The level of protection for IgG anti-spike antibodies was set at 917 BAU/mL for the original Wuhan strain and 980 BAU/mL and 1450 BAU/mL, respectively, for the Delta and Omicron BA.1 variants. Conclusions: The level of protection can be regularly monitored by measuring IgG anti-spike antibody concentrations to allow tailored boosters of SARS-CoV-2 vaccination in this frail and immunocompromised ESKD population. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)
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18 pages, 1091 KiB  
Article
SARS-CoV-2 Antibodies in Response to COVID-19 Vaccination in Underserved Racial/Ethnic Minority People Living with HIV
by Yongjun Huang, Haley R. Fonseca, Leonardo Acuna, Wensong Wu, Xuexia Wang, Samantha Gonzales, Manuel Barbieri, David R. Brown and Marianna K. Baum
Vaccines 2025, 13(5), 517; https://doi.org/10.3390/vaccines13050517 - 13 May 2025
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Abstract
Background: Understanding immune response is essential for preparing for public health crises. COVID-19 vaccination provides robust immunity against SARS-CoV-2, but immunocompromised populations may have weaker immune responses. We assessed SARS-CoV-2 spike (trimer) total IgG/IgM/IgA (total Ig) to investigate immune response to COVID-19 [...] Read more.
Background: Understanding immune response is essential for preparing for public health crises. COVID-19 vaccination provides robust immunity against SARS-CoV-2, but immunocompromised populations may have weaker immune responses. We assessed SARS-CoV-2 spike (trimer) total IgG/IgM/IgA (total Ig) to investigate immune response to COVID-19 vaccination in people living with HIV (PLWH), considering CD4+ T cell count, viral load, substance use, and comorbidities. Methods: This cross-sectional study was conducted in Miami, Florida, between May 2021 and December 2021 as part of the NIH Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative (3U01DA040381-05S1) and the Miami Adult Studies on HIV (MASH) cohort (U01DA040381). Blood samples were collected and SARS-CoV-2 spike (trimer) total Ig was quantified. HIV serostatus, viral load, CD4+ T cell count, and COVID-19 vaccinations were abstracted from medical records. Substance use (tobacco, alcohol, and drug use [marijuana, cocaine, heroin, fentanyl, methamphetamine, amphetamine, hallucinogens, ecstasy, or misuse of prescription drugs]), and comorbidities (hypertension, diabetes, autoimmune disease, obesity, chronic kidney disease, and substance use disorders) were assessed via validated questionnaires. Drug use was confirmed via urine toxicology. Multivariable linear regression was conducted. Results: Median age (n = 1317) was 57.8 years, 49.8% were male, 50% were Black non-Hispanic, 66.2% had received ≥1 dose of a COVID-19 vaccine, and 29.6% were PLWH (71.3% virally suppressed and median CD4+ T cell count > 500 cells/µL). PLWH, compared to people without HIV, were more likely to have received ≥1 dose of a COVID-19 vaccine (76.2% vs. 62.0%, p < 0.001) and present with substance use (77.2% vs. 42.9%, p < 0.001) and comorbidities (72.8% vs. 48.2%, p < 0.001). Vaccinated PLWH, compared to unvaccinated PLWH, had higher CD4+ T cell counts (577.5 vs. 517.5, p = 0.011) and were more likely to be virally suppressed (76.4% vs. 54.8%, p < 0.001). A lower CD4+ T cell count (<200 vs. ≥500, β = −0.400, p = 0.033) and higher HIV viral load (≥200–<5000 vs. <200, β = −0.275, p < 0.001) were associated with lower spike (trimer) total Ig titers, indicating a diminished response to COVID-19 vaccination. Conclusions: A lower CD4+ T cell count and higher HIV viremia were linked to reduced SARS-CoV-2 immunogenicity in racial/ethnic minority PLWH, a population underrepresented in vaccine clinical trials. HIV care providers should target efforts to maintain viral suppression to avoid diminished responses to COVID-19 vaccination. Full article
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13 pages, 238 KiB  
Article
Vaccination Barriers in Brazil: Exploring Hesitancy, Access, and Missed Opportunities in a Cohort of Children (2017–2018)—National Vaccination Coverage Survey Results (2020–2021)
by Letícia Bezerra Faria, Ana Paula França, José Cássio de Moraes and Maria Rita Donalisio
Vaccines 2025, 13(5), 516; https://doi.org/10.3390/vaccines13050516 - 13 May 2025
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Abstract
Background/Objectives: In recent years, Brazil has experienced declining vaccination coverage, raising concerns about vaccine hesitancy and barriers to access. This research analyzes the reasons for non-vaccination among children born in 2017 and 2018 in a metropolitan area of the state of São Paulo [...] Read more.
Background/Objectives: In recent years, Brazil has experienced declining vaccination coverage, raising concerns about vaccine hesitancy and barriers to access. This research analyzes the reasons for non-vaccination among children born in 2017 and 2018 in a metropolitan area of the state of São Paulo in 2020 and 2021. Methods: Data were obtained from a retrospective cohort of children born in 2017 and 2018, living in Campinas, monitored during the first 24 months by vaccination records. A stratified and clustered sample by census sector was performed according to socioeconomic conditions. The reasons for non-vaccination were obtained from interviews with the children’s guardians. Results: A total of 1775 caregivers were interviewed, and 63.1% of children had complete vaccination coverage, with lower socioeconomic groups presenting the highest rates for non-vaccination. The study identified three main groups for non-vaccination: vaccine hesitancy (e.g., fear of side effects, misinformation) in 1.7% of respondents, access difficulties (e.g., service location, financial constraints) in 7.9%, and missed opportunities (e.g., lack of vaccines, administrative barriers) in 16.4%. Conclusions: The findings indicate that the main reported barriers to childhood vaccination are missed opportunities in healthcare services, often due to vaccine shortages or administrative issues, along with social vulnerabilities. Vaccine hesitancy stems from misinformation and fear of side effects. Despite these challenges, families persist in seeking vaccination. However, coverage remains below the national targets, particularly in the second year of life. Targeted public health interventions are urgently needed to improve vaccine confidence, accessibility, and healthcare system efficiency. Full article
(This article belongs to the Special Issue Impact of Immunization Safety Monitoring on Vaccine Coverage)
16 pages, 381 KiB  
Article
Adherence to a Vaccination Schedule in a Simulated HIV Vaccine Efficacy Trial Among Adults in Fishing Communities Around Lake Victoria, Uganda
by Sharon Barbara Nabasumba Kalenge, Andrew Abaasa, Teddy Nakaweesi, Victoria Menya Biribawa, Annet Nanvubya, Ali Ssetaala, Juliet Mpendo, Brenda Okech, Matt A. Price, Bernard S. Bagaya and Noah Kiwanuka
Vaccines 2025, 13(5), 515; https://doi.org/10.3390/vaccines13050515 - 13 May 2025
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Abstract
Background/Objectives: Fishing communities (FCs) around Lake Victoria have been identified as suitable for future HIV vaccine efficacy trials due to their high HIV incidence rates. To inform trial design and implementation, we evaluated adherence to vaccination schedules and study retention in a simulated [...] Read more.
Background/Objectives: Fishing communities (FCs) around Lake Victoria have been identified as suitable for future HIV vaccine efficacy trials due to their high HIV incidence rates. To inform trial design and implementation, we evaluated adherence to vaccination schedules and study retention in a simulated HIV vaccine efficacy trial (SiVET) among adults from two fishing communities in Uganda. Methods: A 12-month prospective cohort study enrolled 250 HIV seronegative adults, aged 18–49 years, from one island and one mainland FC. The hepatitis B vaccine was administered at months 0, 1, and 6 to simulate an HIV vaccine regimen. Those testing HIV positive or pregnant were referred for care. Socio-demographic, behavioral, and clinical data were collected at baseline, 6, and 12 months. Poisson regression models with robust standard errors were used to identify factors associated with vaccination completion and retention. Results: Participants’ age ranged between 25–34 years, with a mean age of 27.6 years (SD = 6.4), and 68% of participants were from the mainland and 22% from the island. The overall vaccination completion rate was 86.5 per 100 person-years of observation (PYO), and was similar between mainland (86.8/100 PYO) and island dwellers (85.6/100 PYO). Male participants were likelier to complete all vaccinations [aRR = 1.1 (95% CI 1.0–1.2)]. Having received a secondary education or higher was also associated with higher vaccination completion compared to the rates for those with primary or no formal education [aRR = 1.1; 95% CI: 1.0–1.2]. Notably, participants who reported illicit drug use [aRR = 1.3; 95% CI: 1.2–1.4] and those engaged in paid sex [aRR = 1.2; 95% CI: 1.1–1.4] were more likely to complete all study visits. Conclusions: Adherence to vaccination schedules was high and consistent between mainland and island populations. These findings confirm that fishing communities are well-suited for future HIV vaccine efficacy trials. Predictors of adherence include male sex, secondary education, illicit drug use, and involvement in paid sex. High adherence rates underscore the feasibility of conducting such trials in this population. Full article
(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)
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13 pages, 2081 KiB  
Article
A Single-Chain Mpox mRNA Vaccine Elicits Protective Immune Response in Mice
by Qian Xu, Rong-Rong Zhang, Mei Wu, Jie Zhang, Zu-Xin Wang, Hang Chi, Chao Zhou, Xiao-Chuan Xiong, Hai-Tao Liu, Cheng-Feng Qin and Qing Ye
Vaccines 2025, 13(5), 514; https://doi.org/10.3390/vaccines13050514 - 13 May 2025
Viewed by 43
Abstract
Background: The re-emerging mpox virus (MPXV) has spread to numerous countries and raised global concern. There is an urgent need for a safe and effective mRNA vaccine candidate against MPXV infection. Previously, we developed a penta-component mRNA vaccine that contained five distinct antigen-encoded [...] Read more.
Background: The re-emerging mpox virus (MPXV) has spread to numerous countries and raised global concern. There is an urgent need for a safe and effective mRNA vaccine candidate against MPXV infection. Previously, we developed a penta-component mRNA vaccine that contained five distinct antigen-encoded mRNAs encapsulated within lipid nanoparticles (LNPs). Here, we sought to develop a single-chain mRNA vaccine that encodes antigens derived from both intracellular mature virion (IMV) and extracellular enveloped virion (EEV). Methods: A single-chain mRNA vaccine encoding a fusion protein comprising the ectodomains of M1R (eM1R) and A35R (eA35R) (MPXVeM1-eA35) was developed and characterized, while an admixed formulation of two individual mRNA-LNPs encoding separate antigens was developed as the control (MPXVeM1+eA35). Meanwhile, based on the same strategy, we designed a single-chain mRNA vaccine encoding dimeric antigens (MPXVeM1-eA35-Fc). Mice were immunized with two doses of the candidate vaccines, and both humoral and cellular immune responses were evaluated. The protective efficacy of the candidate vaccines was evaluated based on body weight monitoring and tissue viral load measurement after challenge with vaccinia virus (VACV). Results: Immunization with two doses of MPXVeM1-eA35 elicited robust levels of neutralizing antibodies and antigen-specific cellular immune response. Importantly, MPXVeM1-eA35 demonstrated protective efficacy in a VACV challenge mouse model and showed superior capacity in preventing weight loss post-challenge compared to MPXVeM1+eA35. Similarly, MPXVeM1-eA35-Fc exhibited comparable or superior immunogenicity and protective efficacy compared to the admixed formulations. Conclusions: The single-chain mRNA vaccine elicited a protective immune response in mice, offering significant advantages in terms of manufacturing processes and quality control. Our single-chain mRNA vaccine platform presents a promising strategy for the next generation design of mpox vaccines and contributes to the mitigation of MPXV endemic worldwide. Full article
(This article belongs to the Section DNA and mRNA Vaccines)
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13 pages, 1186 KiB  
Article
Potential for a Combined Oral Inactivated Whole-Cell Vaccine Against ETEC and Shigella: Preclinical Studies Supporting Feasibility
by Manuela Terrinoni, Jan Holmgren, Kevin Ross Turbyfill, Lillian Van De Verg, Nicole Maier and Richard Walker
Vaccines 2025, 13(5), 513; https://doi.org/10.3390/vaccines13050513 - 13 May 2025
Viewed by 50
Abstract
Background: Enteric disease caused by Shigella, Campylobacter, and enterotoxigenic Escherichia coli (ETEC) represents a significant global health burden, particularly among children in low-resource settings. However, no licensed vaccines are currently available for these bacterial pathogens. Given the wide range of enteric [...] Read more.
Background: Enteric disease caused by Shigella, Campylobacter, and enterotoxigenic Escherichia coli (ETEC) represents a significant global health burden, particularly among children in low-resource settings. However, no licensed vaccines are currently available for these bacterial pathogens. Given the wide range of enteric pathogens and the constraints posed by an increasingly crowded infant immunization schedule, the development of combination vaccines or combined administration of individual oral vaccines may offer a practical approach to address this unmet need. Objectives: In this study, we evaluated the combined administration of two multicomponent oral vaccine candidates: ETVAX, targeting ETEC, and a trivalent whole-cell vaccine targeting Shigella. Methods: The vaccine candidates were administered orally in mice, both individually and in combination, with and without the inclusion of the double-mutant heat-labile toxin (dmLT) adjuvant. Results: The results demonstrated systemic and intestinal-mucosal immune responses to the key protective antigens following both individual and combined vaccine administration. Importantly, the combination of the two vaccines did not compromise the elicitation of specific antibody responses. The inclusion of dmLT as an adjuvant significantly enhanced immune responses to several antigens, highlighting its potential to improve vaccine efficacy. Conclusions: These findings underscore the feasibility of combining ETEC and Shigella vaccine candidates into a single formulation without compromising immunogenicity. This combined approach has the potential to provide broad protective coverage, thereby mitigating the global impact of enteric diseases and streamlining vaccine delivery within existing childhood immunization programs. Our results support further development of this combination vaccine strategy as a promising tool in combating enteric infections and improving health outcomes, particularly among young children in endemic regions who are vulnerable to enteric disease. Full article
(This article belongs to the Special Issue Recent Scientific Advances in Vaccines for Shigella)
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6 pages, 5011 KiB  
Correction
Correction: Park et al. Immunization Effects of a Novel α-Synuclein-Based Peptide Epitope Vaccine in Parkinson’s Disease-Associated Pathology. Vaccines 2023, 11, 1820
by Jun Sung Park, Riaz Ahmad, Kyonghwan Choe, Min Hwa Kang, Tae Ju Park and Myeong Ok Kim
Vaccines 2025, 13(5), 512; https://doi.org/10.3390/vaccines13050512 - 13 May 2025
Viewed by 26
Abstract
The authors would like to make the following corrections to this published paper [...] Full article
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16 pages, 1646 KiB  
Article
Safety, Tolerability, and Immunogenicity of a Recombinant Nonavalent Human Papillomavirus Vaccine (Escherichia coli) in Healthy Chinese Women Aged 18–45 Years: A Phase 1 Clinical Trial
by Mingwei Wei, Weiwei Han, Jing Zhang, Yongjiang Liu, Hongyang Yu, Jingxin Li and Wenjuan Wang
Vaccines 2025, 13(5), 511; https://doi.org/10.3390/vaccines13050511 - 13 May 2025
Viewed by 90
Abstract
Background: Prophylactic human papillomavirus (HPV) vaccination substantially alleviates cervical cancer burden. This study aimed to evaluate the safety, tolerability, and immunogenicity of an Escherichia coli-expressed recombinant nonavalent HPV vaccine. Methods: A dose-escalating phase 1 clinical trial was conducted in Sheyang County, Jiangsu [...] Read more.
Background: Prophylactic human papillomavirus (HPV) vaccination substantially alleviates cervical cancer burden. This study aimed to evaluate the safety, tolerability, and immunogenicity of an Escherichia coli-expressed recombinant nonavalent HPV vaccine. Methods: A dose-escalating phase 1 clinical trial was conducted in Sheyang County, Jiangsu Province, China. Each participant received either the test vaccine or the control vaccine (Gardasil 9) following a 0/2/6-month schedule. Adverse reactions (ARs) within 7 days after vaccination, adverse events (AEs) within 30 days, and serious adverse events (SAEs) throughout the study were recorded. Blood parameters were measured before and 3 days after each dose. Serum immunoglobulin G (IgG) and neutralizing antibodies (nAbs) against nine HPV types were analyzed at months 0, 3, and 7. Results: A total of 160 women aged 18–45 years were enrolled, and 155 participants completed the full vaccination regimen. Within 7 days following vaccination, the incidence of ARs ranged from 56.67% to 90.00%, with the low-dose group showing a significantly higher rate than the control group (p = 0.004). Most AEs were mild or moderate, and no vaccine-related SAEs occurred. No significant differences were observed among the four groups regarding the incidence of abnormal laboratory findings. Seroconversion rates for nAbs and IgG against nine HPV types exceeded 97.92% following three doses. High levels of nAbs and IgG were observed at months 3 and 7, with geometric mean titers (GMTs) showing further increases by month 7. Conclusions: This new recombinant nonavalent HPV vaccine exhibits good tolerability and strong immunogenicity among women aged 18–45 years, supporting further efficacy studies in larger populations. Full article
(This article belongs to the Special Issue Prevention of Human Papillomavirus and Vaccines Strategies)
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24 pages, 592 KiB  
Review
Addressing the Underestimated Burden of RSV in Older Adults in Europe: Epidemiology, Surveillance Gaps, and Public Health Implications
by Floriana D’Ambrosio, Marta Lomazzi, Michael Moore, Ada Maida, Roberto Ricciardi, Ludovica Munno, Monia Lettieri, Elisabetta De Vito, Walter Ricciardi and Giovanna Elisa Calabrò
Vaccines 2025, 13(5), 510; https://doi.org/10.3390/vaccines13050510 - 12 May 2025
Viewed by 251
Abstract
Background/Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of Lower Respiratory Tract Infections (LRTIs), posing a serious threat to vulnerable populations. Although growing evidence highlights its significant impact on older adults, RSV surveillance and data collection remain largely focused on children, underestimating [...] Read more.
Background/Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of Lower Respiratory Tract Infections (LRTIs), posing a serious threat to vulnerable populations. Although growing evidence highlights its significant impact on older adults, RSV surveillance and data collection remain largely focused on children, underestimating the burden in older and high-risk adults. This review aims to synthesize current evidence on the epidemiological and clinical impact of RSV in older adults in Europe, assess existing surveillance strategies, and identify gaps to guide targeted public health responses. Methods: A two-phase research strategy was adopted. First, a comprehensive review of studies published between 2015–2025 was conducted via PubMed, focusing on the RSV burden in high-risk and elderly populations in Europe. Second, a structured web screening was performed to assess the status of existing RSV surveillance systems, focusing on eight selected European countries. Results: The review reported RSV prevalence rates ranging from 1% to 64.7% among older adults, with a high prevalence of comorbidities that exacerbate disease severity. Hospitalization rates varied between 12.6–55.9%, while mortality ranged from 2.15% to 13%, reaching up to 36% in intensive care settings. Surveillance systems for adult RSV infections across Europe remain limited and fragmented, with only 37.5% (3/8) of analyzed countries having dedicated surveillance for adults. Conclusions: RSV represents a substantial and underrecognized threat to older adults, with significant clinical and healthcare implications. Strengthening surveillance, standardizing data collection, and ensuring equitable access to newly available preventive measures are urgent priorities to reduce the disease burden, protect vulnerable populations, and support resilient health systems against future health challenges. Full article
(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)
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18 pages, 6632 KiB  
Review
Vaccine Research Trends in Africa from 2016 to Mid-2024: A Bibliometric Analysis
by Chinwe Iwu-Jaja, Duduzile Ndwandwe, Thobile Malinga, Lindi Mathebula, Akhona Mazingisa and Charles Shey Wiysonge
Vaccines 2025, 13(5), 509; https://doi.org/10.3390/vaccines13050509 - 12 May 2025
Viewed by 183
Abstract
Background: Vaccine research publications play a crucial role in the scientific process by strategically linking the generation of knowledge with its translation into vaccine policy and practice. This study was designed to understand vaccine and immunization research publication trends in Africa to inform [...] Read more.
Background: Vaccine research publications play a crucial role in the scientific process by strategically linking the generation of knowledge with its translation into vaccine policy and practice. This study was designed to understand vaccine and immunization research publication trends in Africa to inform strategic directions for vaccine research and innovation efforts in the continent. Methods: We searched PubMed only for vaccine and immunization-related publications from Africa between 1 January 2016 and 8 August 2024. Metrics such as annual growth rates, geographical distribution, international collaboration, and trend topics were analyzed. We conducted separate analyses for general vaccine research, vaccine clinical trials, and vaccine evidence syntheses (systematic reviews and meta-analyses). Results: Vaccine research in Africa demonstrated an annual growth rate of 55.4% (based on the 10,000 records retrieved due to PubMed’s export limit), while vaccine trials saw a decline of 6.08% during the study period. The trend topics analysis across vaccine research, trials, and reviews showed that topics shifted from a focus on general vaccine development, immunization, and malaria pre-2020 to COVID-19-related topics in 2020, with post-2020 research returning to traditional topics like immunization schedules, vaccine safety, and pediatric and maternal vaccines. Additionally, the COVID-19 pandemic had a profound impact on vaccine research, leading to a surge in publications for vaccine research, trials, and reviews. About 65.8% of vaccine research featured international co-authorship. Vaccine trials had a higher rate of international co-authorship at 79.8%. Conclusion: While vaccine research in general in Africa has increased, vaccine trials do not match this increase. The number of clinical trials remained relatively stagnant, reflecting ongoing challenges in the vaccine research ecosystem, particularly in building and sustaining clinical trial capacity across the region. In addition, disparities in research productivity exist between countries. Research prioritization, strategic collaborations, capacity building for research, and improved research infrastructure require critical consideration. Full article
(This article belongs to the Special Issue Childhood Immunization and Public Health)
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16 pages, 1170 KiB  
Article
Knowledge, Awareness and Vaccination Attitude Towards HPV in Sex and Gender Minorities: A Cross-Sectional Study
by Antonio Di Lorenzo, Paola Berardi, Andrea Martinelli, Francesco Paolo Bianchi, Giovanni Migliore, Silvio Tafuri and Pasquale Stefanizzi
Vaccines 2025, 13(5), 508; https://doi.org/10.3390/vaccines13050508 - 12 May 2025
Viewed by 192
Abstract
Background/Objectives: Sex and gender minorities (SGMs) include individuals who do not comply with sexual binarism and heteronormative standards. They represent a high-risk population for Human Papillomavirus (HPV) infection and potential target of an HPV vaccine offer. This study investigates SGMs’ knowledge, awareness [...] Read more.
Background/Objectives: Sex and gender minorities (SGMs) include individuals who do not comply with sexual binarism and heteronormative standards. They represent a high-risk population for Human Papillomavirus (HPV) infection and potential target of an HPV vaccine offer. This study investigates SGMs’ knowledge, awareness and vaccination attitude regarding HPV. Methods: This is a cross-sectional, questionnaire-based study. The target population was represented by SGMs living in Italy and using social media platforms of SGM rights associations. The study questionnaire was based on the literature and disseminated via said associations’ social media. It included items regarding knowledge and awareness, expressed as seven-point Likert scales, and questions about personal information, sexual anamnesis and vaccination attitude. Data collection started on 1 November 2023 and ended on 8 December 2023. Results: The questionnaire was answered by 177 people. Knowledge and awareness scores were generally high (45.98 ± 6.14 and 34.21 ± 4.62, respectively). Regarding attitude, 31.64% of participants reported being hesitant or refusing HPV vaccination, mainly due to prohibitive costs or low perception of the vaccine’s utility. Higher education was associated with a higher knowledge score (coeff.: 2.25; 95%CI: 0.69–3.82); likewise, a history of HPV-related lesions positively influenced the score (coeff.: 2.47; 95%CI: 0.20–4.75). The awareness score was only increased by a greater number of sexual partners (coeff.: 0.06; 95%CI: 0.01–0.11). Older age was proven to significantly increase the odd of vaccine hesitancy (OR: 1.07; 95%CI: 1.02–1.12). Conclusions: Despite a good level of knowledge and awareness, the study population manifested significant barriers to vaccination. The main ones were related to the vaccine’s cost and lack of medical information. Future efforts should focus on reinforcing vaccine offers to SGMs. Full article
(This article belongs to the Special Issue Promoting HPV Vaccination in Diverse Populations)
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14 pages, 1033 KiB  
Article
The Attitude Toward Seasonal Influenza Vaccine Among Workers of Community Healthcare Centers in Zhejiang Province, China: Barriers and Facilitators
by Jianyong Shen, Shangyan Han, Chao Zhang, Huakun Lv and Yu Hu
Vaccines 2025, 13(5), 507; https://doi.org/10.3390/vaccines13050507 - 12 May 2025
Viewed by 147
Abstract
Background: This study was aimed at understanding the attitude on influenza and influenza vaccination among workers of community healthcare centers (CHCs) and investigating the barriers and facilitators for influenza vaccination. Methods: A cross-sectional study was conducted through an anonymous questionnaire to all workers [...] Read more.
Background: This study was aimed at understanding the attitude on influenza and influenza vaccination among workers of community healthcare centers (CHCs) and investigating the barriers and facilitators for influenza vaccination. Methods: A cross-sectional study was conducted through an anonymous questionnaire to all workers of CHCs in 22 CHCs. Socio-demographic characteristics, reasons for acceptance or refusal of influenza vaccination, influenza vaccination status, and attitude toward influenza vaccination were collected. Suggested strategies for improving influenza vaccine uptake were also surveyed. Descriptive analyses were conducted depending on the distributions of variables. A logistic regression analysis was implemented to examine the association between influenza vaccination status in the 2022/2023 season and the potential predictors. The adjusted odds ratio (AOR) with 95% confidence interval (CI) was calculated. Results: In total, 2205 workers of CHCs participated in this study. Influenza vaccination coverage in the 2022/2023 season was 1.36%. The reason “To avoid influenza” met with the highest level of agreement for acceptance of influenza vaccination (median = 4.36 for 1–5-point Likert scale), while the reason “Not a high-risk group of influenza and possible complications” met with the highest level of agreement for refusal of influenza vaccination (median = 3.72 for 1–5-point Likert scale). The influenza vaccination status was significantly related to professional categories, regular exercise habits, sources of information on influenza vaccination, and attitude on recommending influenza vaccination to patients. The free influenza vaccination and mandatory vaccination policies were the most frequent suggestions for improving influenza vaccination coverage. Conclusions: A lower influenza vaccination coverage was observed in workers of CHCs, and it might be attributed to several risk factors. It was urgent to take actions on improving their understanding of, awareness of, and confidence in influenza vaccination. Free influenza vaccination and vaccination requirement policies might be helpful for enhancing vaccine uptake, especially for physicians and other healthcare workers. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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17 pages, 2925 KiB  
Article
Shigella Mutant with Truncated O-Antigen as an Enteric Multi-Pathogen Vaccine Platform
by Jae-Ouk Kim, Harald Nothaft, Younghye Moon, Seonghun Jeong, Anthony R. Vortherms, Manki Song, Christine M. Szymanski, Jessica White and Richard Walker
Vaccines 2025, 13(5), 506; https://doi.org/10.3390/vaccines13050506 - 10 May 2025
Viewed by 262
Abstract
Background/Objectives: Rising antibiotic resistance underscores the urgent need for effective vaccines against shigellosis. Our previous research identified the Shigella flexneri 2a truncated mutant (STM), a wzy gene knock-out strain cultivated in shake-flasks, as a promising broadly protective Shigella vaccine candidate. Expanding on [...] Read more.
Background/Objectives: Rising antibiotic resistance underscores the urgent need for effective vaccines against shigellosis. Our previous research identified the Shigella flexneri 2a truncated mutant (STM), a wzy gene knock-out strain cultivated in shake-flasks, as a promising broadly protective Shigella vaccine candidate. Expanding on this finding, our current study explores the feasibility of transitioning to a fermentor-grown STM as a vaccine candidate for further clinical development. Methods: The STM and STM-Cj, engineered to express the conserved Campylobacter jejuni N-glycan antigen, were grown in animal-free media, inactivated with formalin, and evaluated for key antigen retention and immunogenicity in mice. Results: The fermentor-grown STM exhibited significantly increased production yields and retained key antigens after inactivation. Immunization with the STM, particularly along with the double-mutant labile toxin (dmLT) adjuvant, induced robust immune responses to the conserved proteins IpaB, IpaC, and PSSP-1. Additionally, it provided protection against homologous and heterologous Shigella challenges in a mouse pulmonary model. The STM-Cj vaccine elicited antibody responses specific to the N-glycan while maintaining protective immune responses against Shigella. These findings underscore the potential of the fermentor-grown STM as a safe and immunogenic vaccine platform for combating shigellosis and possibly other gastrointestinal bacterial infections. Conclusions: Further process development to optimize growth and key antigen expression as well as expanded testing in additional animal models for the assessment of protection against Shigella and Campylobacter are needed to build on these encouraging initial results. Ultimately, clinical trials are essential to evaluate the efficacy and safety of STM-based vaccines in humans. Full article
(This article belongs to the Special Issue Recent Scientific Advances in Vaccines for Shigella)
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13 pages, 833 KiB  
Article
Exploring Patient Trust in Healthcare Provider Influenza Vaccine Information and Recommendations in a Medically Underserved Area of Washington State
by Damianne Brand, Megan Giruzzi, Nick Giruzzi, Kavya Vaitla, Rose Krebill-Prather, Juliet Dang and Kimberly McKeirnan
Vaccines 2025, 13(5), 505; https://doi.org/10.3390/vaccines13050505 - 10 May 2025
Viewed by 210
Abstract
Background/Objective: Patients have historically trusted healthcare providers to be a reliable source of health information. However, with the recent pandemic and subsequent recovery, understanding and developing patients’ trust has become even more important, especially regarding vaccine acceptance. The objective of this work [...] Read more.
Background/Objective: Patients have historically trusted healthcare providers to be a reliable source of health information. However, with the recent pandemic and subsequent recovery, understanding and developing patients’ trust has become even more important, especially regarding vaccine acceptance. The objective of this work is to explore the current level of trust that rural patients have in their healthcare providers concerning influenza vaccination and related recommendations and its impact on vaccine uptake in a rural county in Washington State. Methods: An anonymous survey was conducted by a survey research center using a random sampling of 3000 addresses for people living in Yakima County in Washington State. Yakima County has a high percentage of people who identify as Hispanic or Latino/a and is a medically underserved area. The survey was designed to evaluate factors influencing the decision to be vaccinated against influenza and the level of trust in information from healthcare providers. Results: Results showed that participants who had been vaccinated against influenza in the previous five years were more likely to trust the advice of their primary care provider (p < 0.001), specialty care provider (p < 0.001), pharmacist (p = 0.02), and nurse (p = 0.002). People who were not vaccinated against influenza in the last five years were statistically more likely to report that a recommendation from a healthcare provider would not make a difference in their decision (p < 0.001). People who were vaccinated were more likely to utilize healthcare providers as a source of information about the influenza vaccine (p < 0.001) and people who were unvaccinated were more likely to use their own personal research as a trusted information source (p = 0.04). Conclusions: Healthcare providers continue to be well regarded and trusted by their patients, especially in rurally located counties, though work still needs to be carried out around influenza vaccination importance messaging. This work identified that all healthcare providers need to work collaboratively to reinforce vaccination guideline recommendations and to both provide education and continue successful access-to-vaccination strategies to promote influenza prevention. Full article
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1 pages, 129 KiB  
Correction
Correction: Ma et al. A Plant-Produced Recombinant Fusion Protein-Based Newcastle Disease Subunit Vaccine and Rapid Differential Diagnosis Platform. Vaccines 2020, 8, 122
by Fanshu Ma, Erqin Zhang, Qingmei Li, Qianru Xu, Jiquan Ou, Heng Yin, Kunpeng Li, Li Wang, Xiangyue Zhao, Xiangxiang Niu, Xueyang Li, Shenli Zhang, Yanan Wang, Ruiguang Deng, Enmin Zhou and Gaiping Zhang
Vaccines 2025, 13(5), 504; https://doi.org/10.3390/vaccines13050504 - 9 May 2025
Viewed by 128
Abstract
The authors would like to make the following correction to this published paper [...] Full article
15 pages, 827 KiB  
Systematic Review
Indirect Effects of Universal Infant Rotavirus Vaccination: A Narrative Systematic Review
by Darren Suryawijaya Ong, Matthew Harris, John D. Hart and Fiona M. Russell
Vaccines 2025, 13(5), 503; https://doi.org/10.3390/vaccines13050503 - 9 May 2025
Viewed by 225
Abstract
Background/Objective: Rotavirus is a major cause of acute gastroenteritis (AGE) in children <5 years. While rotavirus vaccines are effective in reducing AGE, limited data on their indirect effects exist. The aim of our narrative systematic review was to summarise the indirect effects of [...] Read more.
Background/Objective: Rotavirus is a major cause of acute gastroenteritis (AGE) in children <5 years. While rotavirus vaccines are effective in reducing AGE, limited data on their indirect effects exist. The aim of our narrative systematic review was to summarise the indirect effects of rotavirus vaccines on unvaccinated children and adults (PROSPERO: CRD42023418015). Methods: Peer-reviewed articles and conference abstracts were searched through Medline, Embase and PubMed on 8 December 2024. Observational studies of national/regional vaccine introduction were included. We included five outcomes: rotavirus–AGE inpatient admissions, rotavirus–AGE outpatient attendances, all-cause AGE inpatient admissions, all-cause AGE outpatient attendances, and stool rotavirus positivity. Outcome measures reported as percent reduction or individual incidence rates for the pre- and post-introduction periods were transformed to incidence rate ratios (IRRs). Median IRRs and interquartile ranges (IQRs) were calculated for each outcome by age group (<5, 5–19, and >18 years). Results: From an initial 757 articles, 44 studies including 9,327,974 participants were included. In unvaccinated children <5 years, there were reductions in rotavirus–AGE admissions (median IRR: 0.62, IQR: 0.40–0.82), rotavirus–AGE outpatient attendances (0.74, 0.16–0.98), all-cause AGE admissions (0.70, 0.56–0.86), and stool rotavirus positivity (0.42, 0.31–0.57), but not all-cause AGE outpatient attendances (0.92, 0.78–1.17). Few studies reported these outcomes for children and adolescents aged 5–19 years and adults >18 years. Indirect effects appeared to be greater in higher income and lower under-five mortality settings. Conclusions: Understanding these indirect benefits is crucial for evaluating the broader impact and cost-effectiveness of rotavirus immunisation programs. Full article
(This article belongs to the Special Issue Advanced Concepts in Vaccines in Public Health)
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6 pages, 159 KiB  
Opinion
Unlocking mRNA Vaccine Potential in Liver Cancer Treatment via Synergistic Bile Acid Modulation
by Yuqian Wang, Rui Han and Changquan Ling
Vaccines 2025, 13(5), 502; https://doi.org/10.3390/vaccines13050502 - 9 May 2025
Viewed by 257
Abstract
This Letter to the Editor explores synergistic mechanisms enhancing mRNA cancer vaccine efficacy through bile acid metabolism modulation in liver cancer treatment. The latest evidence indicates that bile acids significantly impair T cell function within the liver cancer microenvironment, creating an immunosuppressive milieu [...] Read more.
This Letter to the Editor explores synergistic mechanisms enhancing mRNA cancer vaccine efficacy through bile acid metabolism modulation in liver cancer treatment. The latest evidence indicates that bile acids significantly impair T cell function within the liver cancer microenvironment, creating an immunosuppressive milieu that hampers anti-tumor responses. Modulating bile acid composition, particularly increasing ursodeoxycholic acid (UDCA), could reshape the tumor microenvironment (TME) to favor mRNA vaccine-induced T cell activity—a promising strategy to overcome current immunotherapy limitations in liver cancer. Full article
14 pages, 1065 KiB  
Article
Safety and Influenza Infections in Children Aged 6–35 Months Receiving Cell Culture-Derived Inactivated Quadrivalent Influenza Vaccine During the 2023–2024 Influenza Season in South Korea
by Hye Eun Lee, Seong-Beom Park, Hye-Young Kim, Sun Heom Baik, Kyungyeon Jung, Juhwan Kim and Ji Young Park
Vaccines 2025, 13(5), 501; https://doi.org/10.3390/vaccines13050501 - 8 May 2025
Viewed by 315
Abstract
Background/Objectives: Influenza poses a significant risk for young children, particularly those under five. Cell culture-derived influenza vaccines offer advantages in reducing adaptive changes and mitigating egg allergy concerns. SKYCellflu® quadrivalent has been in use since 2015, and this study aimed to assess [...] Read more.
Background/Objectives: Influenza poses a significant risk for young children, particularly those under five. Cell culture-derived influenza vaccines offer advantages in reducing adaptive changes and mitigating egg allergy concerns. SKYCellflu® quadrivalent has been in use since 2015, and this study aimed to assess its safety and influenza infections in children aged 6–35 months in South Korea. Methods: A prospective cohort, non-interventional, multi-center post-marketing surveillance study was conducted from 2020 to 2024. This study presents data from the 2023–2024 influenza season on safety and influenza infections in children aged 6–35 months following SKYCellflu® vaccination. Safety was assessed based on adverse events (AEs) within 28 days post-vaccination, and influenza infections were assessed via phone calls or medical record screening. Results: Among 333 safety set participants, 54.4% reported at least one AE, with most being mild to moderate. The cumulative incidence of influenza infections among 247 ad hoc subsets was 4.5%, and the incidence rate was 1.3 per 100 person-months (95% CI, 0.7–2.4) during the 2023–2024 influenza season. The two-dose regimen in vaccine-naïve infants aged 6–11 months showed a lower cumulative incidence of influenza infection rate (0.8% vs. 3.8%) and incidence rate (0.3 vs. 0.9 per 100 person-months) than the one-dose group (3.8%). No influenza-related hospitalizations occurred within the ad hoc subset. Conclusions: This study demonstrated a tolerable safety profile and the pattern of influenza infections following SKYCellflu® vaccination. Additionally, the two-dose regimen was associated with a lower incidence of influenza infections, suggesting potential benefits in enhancing protection among infants aged 6–11 months. Full article
(This article belongs to the Special Issue Vaccine Development for Influenza Virus)
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26 pages, 7008 KiB  
Article
Single-Domain Antibodies That Specifically Recognize Intact Capsids of Multiple Foot-and-Mouth Disease Serotype O Strains
by Michiel M. Harmsen, Nishi Gupta, Quillan Dijkstra, Sandra van de Water, Marga van Setten and Aldo Dekker
Vaccines 2025, 13(5), 500; https://doi.org/10.3390/vaccines13050500 - 8 May 2025
Viewed by 226
Abstract
Background/Objectives: Intact (146S) foot-and-mouth disease virus (FMDV) particles easily dissociate into 12S particles with a concomitant decreased immunogenicity. Vaccine quality control with 146S-specific single-domain antibodies (VHHs) is hampered by the high strain specificity of most 146S-specific VHHs. This study aimed to isolate 146S-specific [...] Read more.
Background/Objectives: Intact (146S) foot-and-mouth disease virus (FMDV) particles easily dissociate into 12S particles with a concomitant decreased immunogenicity. Vaccine quality control with 146S-specific single-domain antibodies (VHHs) is hampered by the high strain specificity of most 146S-specific VHHs. This study aimed to isolate 146S-specific VHHs that recognize all serotype O strains. Methods: Biopanning was performed with the FMDV strain O/SKR/7/2010 146S, using a secondary library of mutagenized M170F VHH that did not recognize O/SKR/7/2010 or using phage-display libraries from llamas immunized with other serotype O strains. Novel VHHs were yeast-produced and their strain-, particle-, and antigenic-site specificities were determined by ELISA. Results: M170F mutagenesis did not improve the cross-reaction with O/SKR/7/2010. However, selection from immune libraries resulted in four VHHs that exhibited high 146S specificity for all five serotype O strains analyzed. These VHHs presumably recognize all serotype O strains since the five strains analyzed represent different phylogenetic clades. They bind the same antigenic site as M170F, which was previously shown to be a conserved site in serotypes A and O, and which has an altered 3D structure when 146S dissociates into 12S particles. M916F had the lowest limit of detection, which varied from 0.7 to 5.9 ng/mL 146S particles for three serotype O strains. Conclusions: We identified four VHHs (M907F, M910F, M912F, and M916F) that specifically bind 146S particles of probably all serotype O strains. They enable further improved FMDV vaccine quality control. Full article
(This article belongs to the Special Issue Vaccine and Vaccination in Veterinary Medicine)
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Retraction
RETRACTED: Umakanthan et al. COVID-19 Vaccine Hesitancy and Resistance in India Explored through a Population-Based Longitudinal Survey. Vaccines 2021, 9, 1064
by Srikanth Umakanthan, Sonal Patil, Naveen Subramaniam and Ria Sharma
Vaccines 2025, 13(5), 499; https://doi.org/10.3390/vaccines13050499 - 8 May 2025
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Abstract
The journal retracts the article, titled “COVID-19 Vaccine Hesitancy and Resistance in India Explored through a Population-Based Longitudinal Survey” [...] Full article
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