Journal Description
Vaccines
Vaccines
is an international, peer-reviewed, open access journal published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Medicine, Research and Experimental) / CiteScore - Q1 (Pharmacology (medical))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 19.6 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
3.4 (2024);
5-Year Impact Factor:
3.7 (2024)
Latest Articles
Economic Impacts of Initiating Vaccination at 3 Months vs. 6 Months in an Influenza Pandemic in the United States
Vaccines 2025, 13(8), 828; https://doi.org/10.3390/vaccines13080828 (registering DOI) - 1 Aug 2025
Abstract
Background/Objectives: An influenza pandemic is likely to occur in the coming decades and will be associated with substantial healthcare and financial burdens. In this study, we evaluated the potential economic costs of different vaccination scenarios for the US population in the context of
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Background/Objectives: An influenza pandemic is likely to occur in the coming decades and will be associated with substantial healthcare and financial burdens. In this study, we evaluated the potential economic costs of different vaccination scenarios for the US population in the context of a moderate or severe influenza pandemic. Methods: Economic analysis was performed for initiation of pandemic vaccination from 3 months vs. 6 months in the US after declaration of a pandemic. We evaluated three vaccine effectiveness levels (high, moderate, low) and two pandemic severity levels (moderate and severe). Results: No vaccination would lead to total direct and indirect costs of $116 bn in a moderate pandemic and $823 bn in a severe pandemic. Initiation of vaccination at 3 months would result in cost savings versus no vaccination (excluding vaccine price) of $30–84 bn and $260–709 bn in a moderate and severe pandemic, respectively, whereas initiation of vaccination at 6 months would result in cost savings of $4–11 bn and $36–97 bn, respectively. Cost savings of $20 bn and $162 bn would occur in a moderate or severe pandemic, respectively, from use of a low effectiveness vaccine from 3 months instead of a high effectiveness vaccine from 6 months. Conclusions: Rapid initiation of vaccination would have a greater impact than increased vaccine effectiveness in reducing the economic impacts of an influenza pandemic.
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(This article belongs to the Special Issue Innovations Advancing Vaccine Preparedness and Response Capabilities to Counter Pandemic Influenza)
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Open AccessArticle
Integrated Analysis of the Safety Experience in Adults with the Bivalent Respiratory Syncytial Virus Prefusion F Vaccine
by
Kumar Ilangovan, David Radley, Michael Patton, Emma Shittu, Maria Maddalena Lino, Christos Goulas, Kena A. Swanson, Annaliesa S. Anderson, Alejandra Gurtman and Iona Munjal
Vaccines 2025, 13(8), 827; https://doi.org/10.3390/vaccines13080827 (registering DOI) - 1 Aug 2025
Abstract
Background/objectives: This was a post hoc analysis of safety data across the bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccine clinical trial development program. Methods: Data from eight clinical trials in 46,913 immunocompetent adults who received RSVpreF or placebo were analyzed. Local reactions
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Background/objectives: This was a post hoc analysis of safety data across the bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccine clinical trial development program. Methods: Data from eight clinical trials in 46,913 immunocompetent adults who received RSVpreF or placebo were analyzed. Local reactions and systemic events were assessed among non-pregnant ≥18-year-olds (n = 9517); adverse events (AEs) among pregnant and non-pregnant 18–59-year-olds (n = 9238); and vaccine-related AEs among non-pregnant ≥18-year-olds (n = 39,314). Post-marketing data in non-pregnant adults were considered. Results: Local reactions and systemic events were reported more frequently in RSVpreF versus placebo recipients; injection site pain was the most common local reaction (RSVpreF, 18.9%; placebo, 7.4%), and fatigue (23.5%; 18.4%) and headache (19.5%; 15.0%) were the most common systemic events. Percentages of AEs within 1 month after vaccination were similar across groups (RSVpreF, 12.8%; placebo, 13.1%); severe AEs were reported in ≤1.5% of participants. Differences in percentages of individuals reporting vaccine-related AEs between the RSVpreF and placebo groups were <0.2% for all related AEs. Serious AEs throughout the study were reported in ≤14.0% (RSVpreF, 12.6%; placebo, 14.0%). No atrial fibrillation, Guillain-Barré syndrome, or acute polyneuropathy cases were reported. The AE data from post-marketing data sources were consistent with the safety profile from the clinical trial program, with no new safety concerns. Conclusions: Integrated data demonstrated that RSVpreF was well tolerated with a favorable safety profile in non-pregnant and pregnant adults. Ongoing surveillance through real-world use and clinical trial experience continue to support the safety profile of RSVpreF. ClinicalTrials.gov: CT03529773/NCT04071158/NCT04785612/NCT05035212/NCT05096208/NCT05842967/NCT04032093/NCT04424316.
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(This article belongs to the Special Issue Host Immunity and Vaccines for Respiratory Pathogens)
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Open AccessCorrection
Correction: Huang et al. The Safety and Immunogenicity of a Quadrivalent Influenza Subunit Vaccine in Healthy Children Aged 6–35 Months: A Randomized, Blinded and Positive-Controlled Phase III Clinical Trial. Vaccines 2025, 13, 467
by
Lili Huang, Guangfu Li, Yuhui Zhang, Xue Zhao, Kai Wang, Chunyu Jia, Wei Zhang, Jiebing Tan, Xiaofen Chen, Qin Li, Hongyan Jiang, Rui An, Wenna Leng, Yongli Yang, Youcai An, Yanxia Wang and Yaodong Zhang
Vaccines 2025, 13(8), 826; https://doi.org/10.3390/vaccines13080826 (registering DOI) - 1 Aug 2025
Abstract
The authors would like to make the following corrections to this published paper [...]
Full article
Open AccessSystematic Review
Immunogenicity, Safety, and Protective Efficacy of Mucosal Vaccines Against Respiratory Infectious Diseases: A Systematic Review and Meta-Analysis
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Jiaqi Chen, Weitong Lin, Chaokai Yang, Wenqi Lin, Xinghui Cheng, Haoyuan He, Xinhua Li and Jingyou Yu
Vaccines 2025, 13(8), 825; https://doi.org/10.3390/vaccines13080825 (registering DOI) - 31 Jul 2025
Abstract
Background/Objectives: Mucosal vaccines, delivered intranasally or via inhalation, are being studied for respiratory infectious diseases like COVID-19 and influenza. These vaccines aim to provide non-invasive administration and strong immune responses at infection sites, making them a promising area of research. This systematic review
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Background/Objectives: Mucosal vaccines, delivered intranasally or via inhalation, are being studied for respiratory infectious diseases like COVID-19 and influenza. These vaccines aim to provide non-invasive administration and strong immune responses at infection sites, making them a promising area of research. This systematic review and meta-analysis assessed their immunogenicity, safety, and protective efficacy. Methods: The study design was a systematic review and meta-analysis, searching PubMed and Cochrane databases up to 30 May 2025. Inclusion criteria followed the PICOS framework, focusing on mucosal vaccines for COVID-19, influenza, RSV, pertussis, and tuberculosis. Results: A total of 65 studies with 229,614 participants were included in the final analysis. Mucosal COVID-19 vaccines elicited higher neutralizing antibodies compared to intramuscular vaccines (SMD = 2.48, 95% CI: 2.17–2.78 for wild-type; SMD = 1.95, 95% CI: 1.32–2.58 for Omicron), with varying efficacy by route (inhaled VE = 47%, 95% CI: 22–74%; intranasal vaccine VE = 17%, 95% CI: 0–31%). Mucosal influenza vaccines protected children well (VE = 62%, 95% CI: 30–46%, I2 = 17.1%), but seroconversion rates were lower than those of intramuscular vaccines. RSV and pertussis vaccines had high seroconversion rates (73% and 52%, respectively). Tuberculosis vaccines were reviewed systemically, exhibiting robust cellular immunogenicity. Safety was comparable to intramuscular vaccines or placebo, with no publication bias detected. Conclusions: Current evidence suggests mucosal vaccines are immunogenic, safe, and protective, particularly for respiratory diseases. This review provides insights for future research and vaccination strategies, though limitations include varying efficacy by route and study heterogeneity.
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(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines, 2nd Edition)
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Open AccessArticle
Degradation of Poliovirus Sabin 2 Genome After Electron Beam Irradiation
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Dmitry D. Zhdanov, Anastasia N. Shishparenok, Yury Y. Ivin, Anastasia A. Kovpak, Anastasia N. Piniaeva, Igor V. Levin, Sergei V. Budnik, Oleg A. Shilov, Roman S. Churyukin, Lubov E. Agafonova, Alina V. Berezhnova, Victoria V. Shumyantseva and Aydar A. Ishmukhametov
Vaccines 2025, 13(8), 824; https://doi.org/10.3390/vaccines13080824 (registering DOI) - 31 Jul 2025
Abstract
Objectives: Most antiviral vaccines are created by inactivating the virus using chemical methods. The inactivation and production of viral vaccine preparations after the irradiation of viruses with accelerated electrons has a number of significant advantages. Determining the integrity of the genome of the
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Objectives: Most antiviral vaccines are created by inactivating the virus using chemical methods. The inactivation and production of viral vaccine preparations after the irradiation of viruses with accelerated electrons has a number of significant advantages. Determining the integrity of the genome of the resulting viral particles is necessary to assess the quality and degree of inactivation after irradiation. Methods: This work was performed on the Sabin 2 model polio virus. To determine the most sensitive and most radiation-resistant part, the polio virus genome was divided into 20 segments. After irradiation at temperatures of 25 °C, 2–8 °C, −20 °C, or −70 °C, the amplification intensity of these segments was measured in real time. Results: The best correlation between the amplification cycle and the irradiation dose at all temperatures was observed for segment 3D, left. Consequently, this section of the poliovirus genome is the least resistant to the action of accelerated electrons and is the most representative for determining genome integrity. The worst dependence was observed for the VP1 right section, which, therefore, cannot be used to determine genome integrity during inactivation. The electrochemical approach was also employed for a comparative assessment of viral RNA integrity before and after irradiation. An increase in the irradiation dose was accompanied by an increase in signals indicating the electrooxidation of RNA heterocyclic bases. The increase in peak current intensity of viral RNA electrochemical signals confirmed the breaking of viral RNA strands during irradiation. The shorter the RNA fragments, the greater the peak current intensities. In turn, this made the heterocyclic bases more accessible to electrooxidation on the electrode. Conclusions: These results are necessary for characterizing the integrity of the viral genome for the purpose of creating of antiviral vaccines.
Full article
(This article belongs to the Special Issue Recent Scientific Development of Poliovirus Vaccines)
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Open AccessArticle
HPV E6/E7 mRNA Testing in the Follow-Up of HPV-Vaccinated Patients After Treatment for High-Grade Cervical Intraepithelial Neoplasia
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Adolfo Loayza, Alicia Hernandez, Ana M. Rodriguez, Belen Lopez, Cristina Gonzalez, David Hardisson, Itziar de la Pena, Maria Serrano, Rocio Arnedo and Ignacio Zapardiel
Vaccines 2025, 13(8), 823; https://doi.org/10.3390/vaccines13080823 (registering DOI) - 31 Jul 2025
Abstract
Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and
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Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) is proposed as an indicator of viral integration, which is crucial for identifying severe lesions. Additionally, HPV vaccination could reduce recurrence rates in patients treated for high-grade cervical intraepithelial neoplasia. Objective: Our study aimed to assess the clinical utility of E6/E7 mRNA determination in the follow-up of HPV-immunized patients who were treated for HSIL/CIN. Methods: We conducted a retrospective observational study including 407 patients treated for HSIL/CIN. The recurrence rate and the validity parameters of E6/E7 mRNA testing were analyzed. Results: The recurrence rate for high-grade lesions was 1.7%. This low percentage might be related to the vaccination of patients who were not immunized before treatment. The sensitivity of the E6/E7 mRNA test was 88% at the first clinical visit, reaching 100% in the second and third reviews. Specificity was 91% at the first visit, 92% at the second, and 85% at the third. Regarding predictive values, the positive predictive value was 18% at the first visit, 10% at the second, and 14% at the third, while the negative predictive value was 100% across all follow-up visits. Conclusions: The E6/E7 mRNA test appears to be an effective tool for ruling out recurrence after treatment for HSIL/CIN lesions in HPV-immunized patients.
Full article
(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)
Open AccessReview
Immunization as Protection Against Long COVID in the Americas: A Scoping Review
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Gabriela Zambrano-Sánchez, Josue Rivadeneira, Carlos Manterola, Tamara Otzen and Luis Fuenmayor-González
Vaccines 2025, 13(8), 822; https://doi.org/10.3390/vaccines13080822 (registering DOI) - 31 Jul 2025
Abstract
Introduction: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is
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Introduction: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic’s impact, there is a lack of evidence of its efficacy in preventing long COVID in the region. Methods: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables. Results: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies. Conclusions: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes.
Full article
(This article belongs to the Special Issue COVID-19 Vaccination and Public Health: Addressing Global, Regional and Within-Country Inequalities)
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Open AccessReview
Harnessing the Loop: The Perspective of Circular RNA in Modern Therapeutics
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Yang-Yang Zhao, Fu-Ming Zhu, Yong-Juan Zhang and Huanhuan Y. Wei
Vaccines 2025, 13(8), 821; https://doi.org/10.3390/vaccines13080821 (registering DOI) - 31 Jul 2025
Abstract
Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and
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Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and modular delivery platforms are accelerating clinical translation. In this review, we synthesize recent advances in circRNA therapeutics, with a focused analysis of their stability and immunogenic properties in vaccine and drug development. Notably, key synthesis strategies, delivery platforms, and AI-driven optimization methods enabling scalable production are discussed. Moreover, we summarize preclinical and emerging clinical studies that underscore the potential of circRNA in vaccine development and protein replacement therapies. As both a promising expression vehicle and programmable regulatory molecule, circRNA represents a versatile platform poised to advance next-generation biologics and precision medicine.
Full article
(This article belongs to the Special Issue Evaluating the Immune Response to RNA Vaccine)
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Advancing Reversed-Phase Chromatography Analytics of Influenza Vaccines Using Machine Learning Approaches on a Diverse Range of Antigens and Formulations
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Barry Lorbetskie, Narges Manouchehri, Michel Girard, Simon Sauvé and Huixin Lu
Vaccines 2025, 13(8), 820; https://doi.org/10.3390/vaccines13080820 (registering DOI) - 31 Jul 2025
Abstract
One concern in the yearly re-formulation of influenza vaccines is the time-consuming manufacturing of vaccine potency reagents, particularly for emergency responses. The continuous evaluation of modern techniques such as reversed-phase (RP) chromatography is an asset for streamlining this process. One challenge with RP
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One concern in the yearly re-formulation of influenza vaccines is the time-consuming manufacturing of vaccine potency reagents, particularly for emergency responses. The continuous evaluation of modern techniques such as reversed-phase (RP) chromatography is an asset for streamlining this process. One challenge with RP methods, however, is the need to re-optimize methods for antigens that show poor separation, which can be highly dependent on analyst experience and available data. In this study, we leveraged a large RP dataset of influenza antigens to explore machine learning (ML) approaches of classifying challenging separations for computer-assisted method re-optimization across years, products, and analysts. Methods: To address recurring chromatographic issues—such as poor resolution, strain co-elution, and signal absence—we applied data augmentation techniques to correct class imbalance and trained multiple supervised ML classifiers to distinguish between these peak profiles. Results: With data augmentation, several ML models demonstrated promising accuracy in classifying chromatographic profiles according to the provided labels. These models effectively distinguished patterns indicative of separation issues in real-world data. Conclusions Our findings highlight the potential of ML as a computer assisted tool in the evaluation of vaccine quality, offering a scalable and objective approach to chromatogram classification. By reducing reliance on manual interpretation, ML can expedite the optimization of analytical methods, which is particularly needed for rapid responses. Future research involving larger, inter-laboratory datasets will further elucidate the utility of ML in vaccine analysis.
Full article
(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)
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Open AccessReview
Toxoplasma gondii at the Host Interface: Immune Modulation and Translational Strategies for Infection Control
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Billy J. Erazo Flores and Laura J. Knoll
Vaccines 2025, 13(8), 819; https://doi.org/10.3390/vaccines13080819 (registering DOI) - 31 Jul 2025
Abstract
Toxoplasma gondii is an intracellular protozoan found worldwide that is capable of infecting nearly all warm-blooded animals, including humans. Its parasitic success lies in its capacity to create chronic infections while avoiding immune detection, altering host immune responses, and disrupting programmed cell death
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Toxoplasma gondii is an intracellular protozoan found worldwide that is capable of infecting nearly all warm-blooded animals, including humans. Its parasitic success lies in its capacity to create chronic infections while avoiding immune detection, altering host immune responses, and disrupting programmed cell death pathways. This review examines the complex relationship between T. gondii and host immunity, focusing on how the parasite influences innate and adaptive immune responses to survive in immune-privileged tissues. We present recent findings on the immune modulation specific to various parasite strains, the immunopathology caused by imbalanced inflammation, and how the parasite undermines host cell death mechanisms such as apoptosis, necroptosis, and pyroptosis. These immune evasion tactics enable prolonged intracellular survival and pose significant challenges for treatment and vaccine development. We also review advancements in therapeutic strategies, including host-directed approaches, nanoparticle drug delivery, and CRISPR-based technologies, along with progress in vaccine development from subunit and DNA vaccines to live-attenuated candidates. This review emphasizes the importance of T. gondii as a model for chronic infections and points out potential avenues for developing innovative therapies and vaccines aimed at toxoplasmosis and similar intracellular pathogens.
Full article
(This article belongs to the Special Issue Intracellular Parasites: Immunology, Resistance, and Therapeutics)
Open AccessArticle
Babesia bovis Enolase Is Expressed in Intracellular Merozoites and Contains B-Cell Epitopes That Induce Neutralizing Antibodies In Vitro
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Alma Cárdenas-Flores, Minerva Camacho-Nuez, Massaro W. Ueti, Mario Hidalgo-Ruiz, Angelina Rodríguez-Torres, Diego Josimar Hernández-Silva, José Guadalupe Gómez-Soto, Masahito Asada, Shin-ichiro Kawazu, Alma R. Tamayo-Sosa, Rocío Alejandra Ruiz-Manzano and Juan Mosqueda
Vaccines 2025, 13(8), 818; https://doi.org/10.3390/vaccines13080818 (registering DOI) - 31 Jul 2025
Abstract
Background: Bovine babesiosis, caused by the tick-borne apicomplexan parasite Babesia spp., is an economically significant disease that threatens the cattle industry worldwide. Babesia bovis is the most pathogenic species, leading to high morbidity and mortality in infected animals. One promising approach to
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Background: Bovine babesiosis, caused by the tick-borne apicomplexan parasite Babesia spp., is an economically significant disease that threatens the cattle industry worldwide. Babesia bovis is the most pathogenic species, leading to high morbidity and mortality in infected animals. One promising approach to vaccination against bovine babesiosis involves the use of multiple protective antigens, offering advantages over traditional live-attenuated vaccines. Tools such as immunobioinformatics and reverse vaccinology have facilitated the identification of novel antigens. Enolase, a “moonlighting” enzyme of the glycolytic pathway with demonstrated vaccine potential in other pathogens, has not yet been studied in B. bovis. Methods: In this study, the enolase gene from two B. bovis isolates was successfully identified and sequenced. The gene, consisting of 1366 base pairs, encodes a predicted protein of 438 amino acids. Its expression in intraerythrocytic parasites was confirmed by RT-PCR. Two peptides containing predicted B-cell epitopes were synthesized and used to immunize rabbits. Hyperimmune sera were then analyzed by ELISA, confocal microscopy, Western blot, and an in vitro neutralization assay. Results: The hyperimmune sera showed high antibody titers, reaching up to 1:256,000. Specific antibodies recognized intraerythrocytic merozoites by confocal microscopy and bound to a ~47 kDa protein in erythrocytic cultures of B. bovis as detected by Western blot. In the neutralization assay, antibodies raised against peptide 1 had no observable effect, whereas those targeting peptide 2 significantly reduced parasitemia by 71.99%. Conclusions: These results suggest that B. bovis enolase contains B-cell epitopes capable of inducing neutralizing antibodies and may play a role in parasite–host interactions. Enolase is therefore a promising candidate for further exploration as a vaccine antigen. Nonetheless, additional experimental studies are needed to fully elucidate its biological function and validate its vaccine potential.
Full article
(This article belongs to the Special Issue Vaccines against Arthropods and Arthropod-Borne Pathogens)
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Open AccessArticle
The Immunogenicity of Glutaraldehyde Inactivated PTx Is Determined by the Quantity of Neutralizing Epitopes
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Xi Wang, Xinyue Cui, Chongyang Wu, Ke Tao, Shuyuan Pan and Wenming Wei
Vaccines 2025, 13(8), 817; https://doi.org/10.3390/vaccines13080817 (registering DOI) - 31 Jul 2025
Abstract
Background/Objectives: Chemically or genetically detoxified pertussis toxin (PTx) is a crucial antigen component of the acellular pertussis vaccine. Chemical detoxification using glutaraldehyde generally causes significant structural changes to the toxin. However, how these structural changes in PTx affect its antigenic properties remains unclear.
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Background/Objectives: Chemically or genetically detoxified pertussis toxin (PTx) is a crucial antigen component of the acellular pertussis vaccine. Chemical detoxification using glutaraldehyde generally causes significant structural changes to the toxin. However, how these structural changes in PTx affect its antigenic properties remains unclear. Additionally, there is limited knowledge regarding how many alterations in antigenic properties impact immunogenicity. Methods: To investigate the impact of structural changes on antigenic properties, we developed a sandwich ELISA to quantify the neutralizing epitopes on PTx. Subsequently, we analyzed different PTx toxoid (PTd) preparations with the assay. Additionally, we assessed the immunogenicity of various acellular pertussis vaccine candidates containing these PTd preparations. Finally, the assay was applied to evaluate the consistency of commercial batches of PTx and PTd intermediates. Results: The assay demonstrated reasonable specificity, accuracy, and precision, and it was sensitive enough to quantify variations in neutralizing epitopes among different PTd samples that shared the same protein concentration. Importantly, we found a positive correlation between the number of neutralizing epitopes in detoxified PTx and its immunogenicity, indicating that the amount of neutralizing epitopes present determines the immunogenicity of glutaraldehyde-inactivated PTx. Moreover, commercial batches of PTx and PTd intermediates exhibited minor variations in neutralizing epitopes. Conclusions: These findings have significant implications for developing acellular pertussis vaccines as they highlight the importance of preserving the neutralizing epitopes of PTx during detoxification to ensure the vaccine’s effectiveness. This assay is also valuable for the quality control of PTd as it more accurately represents the actual antigenic changes of PTx.
Full article
(This article belongs to the Special Issue New Technology for Vaccines and Vaccine-Preventable Diseases)
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Open AccessFeature PaperArticle
Low Hepatitis B Immunity Among Ukrainian Refugee Children and Adolescents in Poland: Need for Targeted Screening and Vaccination
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Lidia Stopyra, Karolina Banach, Magdalena Wood, Justyna Stala and Anna Merklinger-Gruchała
Vaccines 2025, 13(8), 816; https://doi.org/10.3390/vaccines13080816 (registering DOI) - 31 Jul 2025
Abstract
Background: The 2022 conflict in Ukraine triggered mass migration, leading to a significant influx of Ukrainian refugee children into Poland. This situation raises concerns about hepatitis B virus immunity, as Ukraine’s hepatitis B vaccination coverage has been inconsistent compared to Poland’s high vaccination
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Background: The 2022 conflict in Ukraine triggered mass migration, leading to a significant influx of Ukrainian refugee children into Poland. This situation raises concerns about hepatitis B virus immunity, as Ukraine’s hepatitis B vaccination coverage has been inconsistent compared to Poland’s high vaccination rates. Objective: To evaluate hepatitis B immunity and infection prevalence among Ukrainian refugee children residing in Southern Poland and to assess implications for vaccination strategies in the host country. Methods: A prospective cross-sectional study was conducted on 1322 Ukrainian refugee children (0–18 years) presenting to a pediatric infectious diseases department in Southern Poland between February 2022 and March 2024. Data on vaccination history, demographic characteristics, and selected laboratory parameters, including hepatitis B surface antigen and anti-HBs antibody levels, were collected. Protective immunity was defined as anti-HBs antibody levels ≥10 IU/L. Results: Among the participants (mean age 9.9 years; 50.2% female), 83.2% were reported as vaccinated according to national immunization programs, but only 64.9% demonstrated protective anti-HBs antibody levels. Protective antibody prevalence declined significantly with age, with less than half of adolescents aged 15–18 years showing immunity. Five children (0.4%) were diagnosed with chronic hepatitis B, four of whom were unvaccinated. Conclusions: This study identifies a significant gap in hepatitis B immunity among Ukrainian adolescent refugees residing in Southern Poland, with less than half possessing protective anti-HBs antibody levels. This immunity gap and the high risk of sexual transmission of the hepatitis B virus in adolescents highlight the urgent need for comprehensive surveillance, screening, and catch-up vaccination programs.
Full article
(This article belongs to the Special Issue Vaccination, Public Health and Epidemiology)
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Open AccessArticle
Risk of SARS-CoV-2 Reinfections Among Healthcare Workers of Four Large University Hospitals in Northern Italy: Results of an Online Survey Within the ORCHESTRA Project
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Filippo Liviero, Anna Volpin, Patrizia Furlan, Silvia Cocchio, Vincenzo Baldo, Sofia Pavanello, Angelo Moretto, Fabriziomaria Gobba, Alberto Modenese, Marcella Mauro, Francesca Larese Filon, Angela Carta, Maria Grazia Lourdes Monaco, Gianluca Spiteri, Stefano Porru and Maria Luisa Scapellato
Vaccines 2025, 13(8), 815; https://doi.org/10.3390/vaccines13080815 (registering DOI) - 31 Jul 2025
Abstract
Background/Objectives: This retrospective multicenter study, conducted within the ORCHESTRA Project, investigated SARS-CoV-2 reinfections among 5777 healthcare workers (HCWs) from four University Hospitals (Modena, Verona, Padova and Trieste) in northern Italy, aiming to assess the risk of reinfection and its determinants, comparing the clinical
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Background/Objectives: This retrospective multicenter study, conducted within the ORCHESTRA Project, investigated SARS-CoV-2 reinfections among 5777 healthcare workers (HCWs) from four University Hospitals (Modena, Verona, Padova and Trieste) in northern Italy, aiming to assess the risk of reinfection and its determinants, comparing the clinical characteristics of reinfections with those of first infections, and examining the impact of preventive measures and vaccination strategies. Methods: HCWs completed an online questionnaire between June and August 2022. The survey collected demographic, occupational, and clinical data, including information on first infections and reinfections. Statistical analyses were performed using SPSS 28.0, through bivariate and multivariate approaches. Results: Response rates were 41.8% for Modena, 39.5% for Verona, 17.9% for Padova, and 17.4% for Trieste. Among the respondents, 4.8% (n = 276) experienced 2 infections and 0.5% (n = 27) reported 3 infections, out of a total of 330 reinfection cases. Additionally, 43.0% (n = 2787) reported only one infection, while 51.5% were never infected. Reinfection rates increased across five study phases (based on the epidemiological context), likely due to the emergence of new SARS-CoV-2 variants. A booster vaccine dose significantly reduced reinfection risk. Higher reinfection risk was found among HCWs aged ≤30 years, those with chronic respiratory diseases, and those working in COVID-19 wards, particularly nurses and allied health professionals. Reinfections were associated with a lower frequency of symptoms both during the period of swab positivity and after a negative swab, as well as with a shorter duration of swab positivity. No significant differences in symptom duration were found between first infections and reinfections. Conclusions: Despite its limitations, the online questionnaire proved a useful tool. Natural infection and vaccination reduced both reinfection risk and symptom severity. Prior infections should be considered in planning vaccination schedules and prioritizing HCWs.
Full article
(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)
Open AccessArticle
Resurgence of Pertussis in the Autonomous Province of Vojvodina, Serbia: Shifting Seasonality, Age Patterns, and the Need for Booster Immunization
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Mioljub Ristić, Vladimir Vuković, Smiljana Rajčević, Snežana Medić, Marko Koprivica and Vladimir Petrović
Vaccines 2025, 13(8), 814; https://doi.org/10.3390/vaccines13080814 (registering DOI) - 31 Jul 2025
Abstract
Background: Despite decades of high childhood vaccination coverage, pertussis has re-emerged in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia. We aimed to describe the temporal, seasonal, and age-specific patterns of pertussis in AP Vojvodina and to analyze trends by vaccination status in
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Background: Despite decades of high childhood vaccination coverage, pertussis has re-emerged in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia. We aimed to describe the temporal, seasonal, and age-specific patterns of pertussis in AP Vojvodina and to analyze trends by vaccination status in order to highlight changes in epidemiology and potential gaps in vaccine-induced protection. Methods: We retrospectively analyzed 2796 pertussis cases reported between January 1997 and December 2024, examining temporal, seasonal, and age-specific trends, stratifying by vaccination status across four consecutive periods (1997–2003, 2004–2010, 2011–2017, and 2018–2024). Results: Throughout the 28-year period, after low and sporadic cases in the pre-2012 period, a dramatic rise was observed in 2014, 2017, and 2018, culminating in the highest annual number of reported cases in 2024 (1011 cases). Throughout this period, primary vaccination coverage with the DTwP/DTaP three-dose series ranged between 91% and 98%, while first booster coverage gradually declined from 98% in the early 2000s to 83% in 2024. Regarding seasonality, a sharp increase in cases began in 2012, peaking in November 2023 (>350 cases) and early 2024 (312 in January, 268 in February), with a seasonal shift from summer peaks in the 2011–2017 period to higher incidence rates during colder months more recently. Adolescents aged 10–14 years had the highest cumulative incidence (1149.4/100,000), followed by infants under 12 months (978.5/100,000), despite the latter representing fewer absolute cases. The proportion of pertussis in fully vaccinated individuals rose from 6.3% (1997–2003) to 49.7% (2018–2024). Conclusions: These findings suggest that booster immunization in adolescence and routine maternal vaccination during pregnancy could reduce transmission, particularly to infants. Enhanced surveillance and updated immunization policies are critical to mitigating future pertussis outbreaks.
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(This article belongs to the Special Issue Epidemiology of Diseases Preventable by Vaccination)
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Open AccessArticle
Vaccine Attitudes, Knowledge, and Confidence Among Nursing, Pediatric Nursing, and Midwifery Undergraduate Students in Italy
by
Ersilia Buonomo, Daniele Di Giovanni, Gaia Piunno, Stefania Moramarco, Giuliana D’Elpidio, Ercole Vellone, Enkeleda Gjini, Mariachiara Carestia, Cristiana Ferrari and Luca Coppeta
Vaccines 2025, 13(8), 813; https://doi.org/10.3390/vaccines13080813 - 30 Jul 2025
Abstract
Background: Vaccine hesitancy (VH) represents a growing concern among healthcare professionals and students, potentially undermining public health efforts. Nursing, pediatric nursing, and midwifery students are future vaccinators and educators, making it essential to understand their attitudes, knowledge, and confidence toward vaccination. This study
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Background: Vaccine hesitancy (VH) represents a growing concern among healthcare professionals and students, potentially undermining public health efforts. Nursing, pediatric nursing, and midwifery students are future vaccinators and educators, making it essential to understand their attitudes, knowledge, and confidence toward vaccination. This study aims to assess vaccine-related perceptions and behaviors among these student populations in an Italian university. Methods: A cross-sectional survey was conducted between November 2022 and February 2024 at the University of Rome “Tor Vergata.” A structured, anonymous questionnaire, including the Vaccination Attitudes Examination (VAX) scale, vaccine knowledge items, and sources of information, was administered to students in nursing (n = 205), pediatric nursing (n = 46), and midwifery (n = 21). Statistical analyses included descriptive statistics, ANOVA, post hoc tests, and Mann–Whitney U tests. Results: Among the 272 participants, 20.6% reported refusing at least one recommended vaccine, and 18.4% delayed vaccination for non-medical reasons. Vaccine knowledge and confidence increased significantly with academic progression (p < 0.001). Midwifery students showed both the highest concern for long-term vaccine effects and the greatest confidence in vaccine safety. Institutional and scientific sources were the most trusted, though traditional and non-institutional media also influenced perceptions, particularly among midwifery students. Conclusions: Despite high COVID-19 vaccine uptake, VH persists among health professional students. Discipline-specific patterns highlight the need for early, targeted educational strategies to enhance vaccine literacy and reduce hesitancy. Tailored training may empower future professionals to become informed and credible advocates for vaccination.
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(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 2nd Edition)
Open AccessArticle
Frequency, Timing, Burden and Recurrence of Adverse Events Following Immunization After HPV Vaccine Based on a Cohort Event Monitoring Study in the Netherlands
by
Monika Raethke, Jeroen Gorter, Rachel Kalf, Leontine van Balveren, Rana Jajou and Florence van Hunsel
Vaccines 2025, 13(8), 812; https://doi.org/10.3390/vaccines13080812 (registering DOI) - 30 Jul 2025
Abstract
Background/Objectives: The aim of this study was to systematically assess Adverse Events Following Immunization (AEFI) among children following administration of the human papillomavirus (HPV) vaccine (Cervarix®) included in the Dutch National Immunization Program (NIP) and to characterize the pattern and recurrence
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Background/Objectives: The aim of this study was to systematically assess Adverse Events Following Immunization (AEFI) among children following administration of the human papillomavirus (HPV) vaccine (Cervarix®) included in the Dutch National Immunization Program (NIP) and to characterize the pattern and recurrence risk of AEFI after HPV revaccination. Methods: A longitudinal cohort event monitoring study, using patient-reported outcomes was used among recipients of the HPV vaccine at 10 years of age. Data were available for 3063 children following the first HPV vaccination and for 2209 children following the second HPV vaccination. Results: The most commonly reported AEFI following HPV vaccination were injection site reactions—reported by 46.5% of participants after the first dose and 31.9% after the second dose—followed by headache (8.2% and 3.9%, respectively) and joint pain (4.5% and 3.7%, respectively). Participants who received both HPV vaccine doses reported more AEFI after the first dose than after the second. Among girls, 61.2% reported at least one AEFI following the first dose, compared to 44.2% after the second dose. For boys, these percentages were 55.3% and 38.5%, respectively. This difference was statistically significant (p = 0.002). For some AEFI, such as injection site reactions, there appears to be a potential increased risk of recurrence following the second dose. Conclusions: This prospective longitudinal cohort event monitoring study showed that AEFI were more frequent after the first HPV dose and more frequent for girls compared to boys. An increased risk of recurrence was seen for AEFI, such as injection site reactions and headache. Furthermore, this study provides insight into the course of AEFI and the extent to which children were affected by these symptoms based on real-world data.
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(This article belongs to the Section Human Papillomavirus Vaccines)
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Open AccessSystematic Review
Interventions to Improve Vaccination Uptake Among Adults: A Systematic Review and Meta-Analysis
by
Anelisa Jaca, Lindi Mathebula, Thobile Malinga, Kimona Rampersadh, Masibulele Zulu, Ameer Steven-Jorg Hohlfeld, Charles Shey Wiysonge, Julie C. Jacobson Vann and Duduzile Ndwandwe
Vaccines 2025, 13(8), 811; https://doi.org/10.3390/vaccines13080811 (registering DOI) - 30 Jul 2025
Abstract
Background: Immunization is a highly effective intervention for controlling over 20 life-threatening infectious diseases, significantly reducing both morbidity and mortality rates. One notable achievement in vaccination efforts was the global eradication of smallpox, which the World Health Assembly declared on 8 May 1980.
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Background: Immunization is a highly effective intervention for controlling over 20 life-threatening infectious diseases, significantly reducing both morbidity and mortality rates. One notable achievement in vaccination efforts was the global eradication of smallpox, which the World Health Assembly declared on 8 May 1980. Additionally, there has been a remarkable 99.9% reduction in wild poliovirus cases since 1988, decreasing from more than 350,000 cases that year to just 30 cases in 2022. Objectives: The objective of this review was to assess the effects of various interventions designed to increase vaccination uptake among adults. Search Methods: A thorough search was conducted in the CENTRAL, Embase Ovid, Medline Ovid, PubMed, Web of Science, and Global Index Medicus databases for primary studies. This search was conducted in August 2021 and updated in November 2024. Selection Criteria: Randomized trials were eligible for inclusion in this review, regardless of publication status or language. Data Analysis: Two authors independently screened the search outputs to select potentially eligible studies. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for each randomized controlled trial (RCT). A meta-analysis was conducted using a random-effects model, and the quality of the evidence was assessed using the GRADE approach. Main Results: A total of 35 randomized controlled trials met the inclusion criteria and were included in this review, with the majority conducted in the United States. The interventions targeted adults aged 18 and older who were eligible for vaccination, involving a total of 403,709 participants. The overall pooled results for interventions aimed at increasing influenza vaccination showed a risk ratio of 1.41 (95% CI: 1.15, 1.73). Most studies focused on influenza vaccination (18 studies), while the remaining studies examined various other vaccines, including those for hepatitis A, COVID-19, hepatitis B, pneumococcal disease, tetanus, diphtheria, pertussis (Tdap), herpes zoster, and human papillomavirus (HPV). The results indicate that letter reminders were slightly effective in increasing influenza vaccination uptake compared to the control group (RR: 1.75, 95% CI: 0.97, 1.16; 6 studies; 161,495 participants; low-certainty evidence). Additionally, participants who received education interventions showed increased levels of influenza vaccination uptake compared to those in the control group (RR: 1.88, 95% CI: 0.61, 5.76; 3 studies; 1318 participants; low-certainty evidence). Furthermore, tracking and outreach interventions also led to an increase in influenza vaccination uptake (RR: 1.87, 95% CI: 0.78, 4.46; 2 studies; 33,752 participants; low-certainty evidence). Conclusions: Letter reminders and educational interventions targeted at recipients are effective in increasing vaccination uptake compared to control groups.
Full article
(This article belongs to the Special Issue SARS-CoV-2, Influenza and Other Respiratory Viruses: Preventive Measures Affecting the Determinants of Health and Disease)
Open AccessArticle
Multifaceted Determinants of Varicella Vaccination Uptake Among Children Aged 1–10 Years in China: Findings of a Population-Based Survey Among 996 Parents
by
Weijun Peng, Yuan Fang, Hongbiao Chen, Minjie Zhang, Yadi Lin and Zixin Wang
Vaccines 2025, 13(8), 810; https://doi.org/10.3390/vaccines13080810 - 30 Jul 2025
Abstract
Background/Objectives: Chickenpox is an ongoing health threat for young children. This study aimed to investigate varicella vaccination uptake among children and its determinants at both the individual and interpersonal levels. Methods: A cross-sectional survey of parents of children aged 0–15 years and with
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Background/Objectives: Chickenpox is an ongoing health threat for young children. This study aimed to investigate varicella vaccination uptake among children and its determinants at both the individual and interpersonal levels. Methods: A cross-sectional survey of parents of children aged 0–15 years and with administrative health records was conducted between September and October 2024 in Shenzhen, China. Participants were recruited through multistage random sampling. This analysis was based on a subsample of 996 parents whose children were 1–10 years old and without a prior history of chickenpox. Multivariate logistic regression models were fitted. Results: Among the participants, 47.0% reported that their children had received a varicella vaccination. Parents who believed that chickenpox was highly contagious (adjusted odds ratios [AOR]: 1.62, 95% confidence interval [CI]: 1.23, 2.13), perceived more benefits (AOR: 1.22, 95% CI: 1.05, 1.41) and cues to action (AOR: 1.33, 95% CI: 1.04, 1.69), and exhibited greater self-efficacy (AOR: 1.40, 95% CI: 1.09, 1.80) related to children’s varicella vaccination reported higher varicella vaccination uptake for their children. Greater perceived barriers related to vaccination (AOR: 0.89, 95% CI: 0.83, 0.95) and dysfunctional interactions with children (AOR: 0.97, 95% CI: 0.94, 0.99) were associated with lower varicella vaccination uptake for children. In addition, higher exposure to information encouraging parents to vaccinate their children against chickenpox (AOR: 1.24, 95%CI: 1.08, 1.41) and thoughtful consideration of the veracity of the information were associated with higher varicella vaccination uptake among children (AOR: 1.19, 95% CI: 1.05, 1.36). Conclusions: There is a strong need to promote varicella vaccination for children in China.
Full article
(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 2nd Edition)
Open AccessBrief Report
End-of-Season Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza in Outpatient Settings, Beijing, China: A Test-Negative Design
by
Jiaojiao Zhang, Zhaomin Feng, Ying Shen, Weixian Shi, Ying Sun, Jiachen Zhao, Dan Wu, Jia Li, Chunna Ma, Wei Duan, Jiaxin Ma, Yingying Wang, Lu Zhang, Xiaodi Hu, Quanyi Wang, Daitao Zhang and Peng Yang
Vaccines 2025, 13(8), 809; https://doi.org/10.3390/vaccines13080809 - 30 Jul 2025
Abstract
This study aimed to estimate the end-of-season influenza vaccine effectiveness (VE) for the 2024/25 season in Beijing, China. Methods: We used a test-negative design (TND) to assess influenza VE among outpatients with influenza-like illness (ILI) enrolled through the influenza virological surveillance in sentinel
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This study aimed to estimate the end-of-season influenza vaccine effectiveness (VE) for the 2024/25 season in Beijing, China. Methods: We used a test-negative design (TND) to assess influenza VE among outpatients with influenza-like illness (ILI) enrolled through the influenza virological surveillance in sentinel hospitals in Beijing from week 44, 2024 to week 14, 2025. Cases were ILI patients who tested positive for influenza; controls were those who tested negative. Results: Among 18,405 ILI patients tested, 3690 (20.0%) were positive for influenza, with A(H1N1)pdm09 as the predominant strain (98.9%). The overall influenza vaccination coverage was 12.4%. Adjusted VE was 48.3% (95%CI: 40.4%–55.3%) against any influenza and 48.2% (95%CI: 40.3%–55.1%) against A(H1N1)pdm09, with the highest VE observed in adults aged 18–59 years (79.0%). The adjusted VE was similar for those vaccinated in 2023/24 only (53.1%) or both 2023/24 and 2024/25 seasons (50.8%), but lower for those vaccinated only in the 2024/25 season (48.5%). The adjusted VE was higher during the epidemic period (52.5%) than in the pre-epidemic (48.1%) and post-epidemic (35.3%) periods. Conclusions: Our findings indicate moderate VE against laboratory-confirmed influenza, especially A(H1N1)pdm09, during the end of the 2024/25 season in Beijing, China. Influenza vaccination provided protective effects across different epidemic periods. These timely estimates support ongoing public health communication and immunization strategies.
Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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