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
Multi-Component Vaccine Candidates Against Non-Typeable Haemophilus influenzae
Vaccines 2025, 13(9), 892; https://doi.org/10.3390/vaccines13090892 - 22 Aug 2025
Abstract
Background: Haemophilus influenzae (Hi), a Gram-negative bacterium, is divided into two broad categories: encapsulated and non-capsulated isolates, also called non-typeable Hi isolates (NTHi). NTHi has become prevalent since the introduction of the vaccine against Hi of serotype b. Hi can cause local
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Background: Haemophilus influenzae (Hi), a Gram-negative bacterium, is divided into two broad categories: encapsulated and non-capsulated isolates, also called non-typeable Hi isolates (NTHi). NTHi has become prevalent since the introduction of the vaccine against Hi of serotype b. Hi can cause local infections on respiratory mucosal surfaces and urogenital infections, which can lead to septic abortion in pregnant women. It can also cause invasive infections such as meningitis and septicemia. Moreover, NTHi isolates are becoming increasingly resistant to antibiotics. Vaccines targeting NTHi are not yet available. As these NTHi isolates are not encapsulated, vaccines should target proteins at the bacterial surface. However, vaccine development is hindered by the high variability of these proteins. We aimed to identify conserved outer membrane proteins (OMPs) for vaccines against NTHi. Methods: We analyzed core-genome multilocus sequence typing (cgMLST) of 1144 genomes of Hi collected between 2017 and 2022 and, of these, identified 514 conserved genes that encoded OMPs. We focused on two specific OMPs: Haem1295, encoding the protein P5 (P5), and Haem1040, encoding the protein 26 (P26). P5 is known to bind human complement regulatory protein factor H (FH), while both P5 and P26 are involved in enhancing immune responses. The genes encoding these proteins were cloned, overexpressed, purified, and tested in both active and passive protection models using systemic infection in mice. Results: P5 and P26 were found to be immunogenic during human infections. Vaccination with these proteins conferred protection against both homologous and heterologous NTHi isolates in mice, suggesting broad cross-protection. Conclusions: P5 and P26 are promising vaccine candidates showing cross-protection against NTHi and offering the additional benefit of targeting bacterial virulence factors, enhancing vaccine efficacy against NTHi isolates.
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(This article belongs to the Section Vaccine Design, Development, and Delivery)
Open AccessCommentary
Understanding the Implications of Delaying Seasonal Influenza Vaccine Recommendations: An Industry Perspective
by
Steven Rockman and Karen Laurie
Vaccines 2025, 13(9), 891; https://doi.org/10.3390/vaccines13090891 - 22 Aug 2025
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Multiple studies have assessed the potential for improvement for genetic and antigenic match of influenza vaccines to circulating viruses by altering the timing of vaccine strain decisions. The advent of new technologies for vaccination has generated global discussion around moving the seasonal influenza
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Multiple studies have assessed the potential for improvement for genetic and antigenic match of influenza vaccines to circulating viruses by altering the timing of vaccine strain decisions. The advent of new technologies for vaccination has generated global discussion around moving the seasonal influenza strain recommendations closer to the start of the vaccination period. The window between influenza vaccine strain recommendations and the availability of vaccine supply for immunization comprises sequential processes required to produce vaccine components, reagents for manufacture and release, and regulatory approvals. This commentary examines one company’s perspective on requirements for enabling manufacture and release of seasonal influenza vaccine in more detail, describes preparations to reduce risk, and highlights the potential impact on vaccine supply for all platforms (egg, cell, mRNA) when strain decisions are issued closer to the desired vaccination timing.
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Open AccessReview
Influenza Virus: Global Health Impact, Strategies, Challenges, Role of Nanotechnolgy in Influenza Vaccine Development
by
Shabi Parvez, Anushree Pathrathota, Arjun L. Uppar, Ganesh Yadagiri and Shyam Lal Mudavath
Vaccines 2025, 13(9), 890; https://doi.org/10.3390/vaccines13090890 - 22 Aug 2025
Abstract
Influenza is a serious and global health issue, and it is a major cause of morbidity, fatality, and economic loss every year. Seasonal vaccines exist but are not very effective due to strain mismatches, delays in production, and antigenic drift. This comprehensive overview
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Influenza is a serious and global health issue, and it is a major cause of morbidity, fatality, and economic loss every year. Seasonal vaccines exist but are not very effective due to strain mismatches, delays in production, and antigenic drift. This comprehensive overview discusses the current situation of influenza vaccination, including the numerous types of vaccines—inactivated, live attenuated, and recombinant vaccines—and their effectiveness, efficacy, and associated challenges. It highlights the effects of the COVID-19 pandemic on the trends of influenza vaccination and the level to which innovation should be practiced. In the future universal influenza vaccines will be developed that target conserved viral antigens to provide long-term protection to people. In the meantime, novel vaccine delivery platforms, such as mRNA technology, virus-like particle (VLP), and nanoparticle-based systems, and less cumbersome and invasive administration routes, as well as immune responses are also under development to increase access and production capacity. Collectively, these innovations have the potential to not only reduce the global influenza epidemic but also to change the way influenza is prevented and prepare the world for a pandemic.
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(This article belongs to the Special Issue Vaccine Development for Influenza Virus)
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Open AccessArticle
Peptide-Based Anti-PCSK9 Product for Long-Lasting Management of Hypercholesterolemia
by
Suresh R. Giri, Akshyaya Chandan Rath, Chitrang J. Trivedi, Bibhuti Bhusan Bhoi, Sandip R. Palode, Vighnesh N. Jadhav, Hitesh Bhayani, Avanishkumar Singh, Chintan Patel, Tushar M. Patel, Niraj M. Sakhrani, Jitendra H. Patel, Niraj A. Shah, Rajendra Chopade, Rajesh Bahekar, Vishwanath Pawar, Rajesh Sundar, Sanjay Bandyopadhyay and Mukul R. Jain
Vaccines 2025, 13(9), 889; https://doi.org/10.3390/vaccines13090889 - 22 Aug 2025
Abstract
Background/Objectives: Hypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective,
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Background/Objectives: Hypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective, their short half-life requires frequent dosing and incurs high treatment costs. This study evaluates a novel peptide-based Anti-PCSK9 product aimed at providing sustained LDL-C reduction. Methods: A novel PCSK9 based-peptide conjugated to diphtheria toxoid (DT) was evaluated in various preclinical models: high-fat diet-fed C57BL/6 mice, APOB100/hCETP transgenic mice, BALB/c mice and normocholesterolemic non-human primates. Immunogenicity (Anti-PCSK9 antibody titers, binding affinity by SPR), pharmacodynamics (LDL-C levels, inhibition of PCSK9-LDLR interaction) and safety were assessed. Toxicity was evaluated in rodents, rabbits and dogs through clinical monitoring, histopathology, organ function and safety pharmacology studies. Results: The Anti-PCSK9 product induced robust and long-lasting immune response in all models antibody titers in BALB/c mice peaked by week 6 and persisted for 12 months. LDL-C reductions of 44% in APOB100/hCETP mice and 37% in C57BL/6 mice correlated with high antibody titers and strong PCSK9-binding affinities (85 and 49 RU), leading to 59% and 58% inhibition of PCSK9-LDLR interaction, respectively. Non-human primates showed sustained responses. No systemic toxicity was observed; injection-site reactions were mild and reversible. No adverse effects were detected on cardiovascular, neurological, or respiratory systems. Conclusions: This peptide-based Anti-PCSK9 therapy offers sustained efficacy and safety, representing a promising long-acting alternative for managing hypercholesterolemia.
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(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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Open AccessReview
A Review of Insights on Vaccination Against Respiratory Viral Infections in Africa: Challenges, Efforts, Impacts, and Opportunities for the Future
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Paul Gasana, Noel Gahamanyi, Augustin Nzitakera, Frédéric Farnir, Daniel Desmecht and Leon Mutesa
Vaccines 2025, 13(9), 888; https://doi.org/10.3390/vaccines13090888 - 22 Aug 2025
Abstract
Background: Respiratory viral infections such as influenza, COVID-19, and respiratory syncytial virus (RSV) are considered as major public health threats in Africa. Despite global advancements in vaccine development, persistent inequities in access, delivery infrastructure, and public trust limit the continent’s capacity to
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Background: Respiratory viral infections such as influenza, COVID-19, and respiratory syncytial virus (RSV) are considered as major public health threats in Africa. Despite global advancements in vaccine development, persistent inequities in access, delivery infrastructure, and public trust limit the continent’s capacity to control these diseases effectively. This review aimed at providing insights on challenges, efforts, impacts, and opportunities for the future related to vaccination against respiratory viral infections in Africa. Methods: This narrative review synthesizes the peer-reviewed literature and global health reports to examine vaccination efforts against respiratory viruses in Africa. The analysis focuses on disease burden, vaccine coverage, barriers to uptake, enabling factors, progress in local vaccine production, and strategies for integrating vaccines into national immunization programs (NIPs). Results: Respiratory vaccines have significantly reduced hospitalizations and mortality among high-risk groups in African countries. Nonetheless, key challenges, including limited cold chain capacity, vaccine hesitancy, donor-reliant supply chains, and under-resourced health systems, continue to undermine vaccine delivery. Successful interventions include community mobilization, use of mobile health technologies, and leveraging existing immunization platforms. Emerging initiatives in local vaccine manufacturing, including Rwanda’s modular mRNA facility and Senegal’s Institut Pasteur, signal a shift toward regional self-reliance. Conclusions: Maximizing the impact of respiratory vaccines in Africa requires a multifaceted strategy: integrating vaccines into NIPs, strengthening domestic production, expanding cold chain and digital infrastructure, and addressing sociocultural barriers through community-driven communication. These efforts are essential to achieving vaccine equity, health resilience, and pandemic preparedness across the continent.
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(This article belongs to the Special Issue Understanding Infectious Disease Vaccinations: Implications for Health and Safety)
Open AccessArticle
A QS21+ CpG-Adjuvanted Rabies Virus G Subunit Vaccine Elicits Superior Humoral and Moderate Cellular Immunity
by
Han Cao, Hui Li, Wenzhi Liu, Ning Luan, Jingping Hu, Meijun Kong, Jie Song and Cunbao Liu
Vaccines 2025, 13(8), 887; https://doi.org/10.3390/vaccines13080887 - 21 Aug 2025
Abstract
Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed
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Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity. Methods: We developed a novel QS21+CpG-adjuvanted RABV-G subunit vaccine and systematically compared its performance against three control formulations: mRNA vaccine composed of H270P-targeted mutation packaged in lipid nanoparticles (LNP), named LNP-mRNA-G-H270P, commercial inactivated vaccine, and alum-adjuvanted RABV-G subunit vaccine. Results: The result show that the G+QS21+CpG subunit vaccine elicited superior humoral immunity, as evidenced by significantly higher RABV-G-specific IgG titers and virus-neutralizing antibody responses compared to all other groups. The LNP-mRNA-G-H270P vaccine maintained its expected cellular immunity advantage, with the G+QS21+CpG group exhibiting moderately reduced but still significant levels of IFN-γ-secreting splenocytes and levels of IL-2 in the supernatant of spleen cells, as well as IFN-γ-producing CD4+ T cells. Both LNP-mRNA-G-H270P and G+QS21+CpG vaccine groups provided 100% protection against lethal challenge (50LD50 RABV). Conclusions: These findings provide novel vaccine/adjuvant strategies for rabies while elucidating platform-specific immunogenicity patterns, offering critical insights for pathogens requiring balanced humoral/cellular immunity.
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(This article belongs to the Section Vaccine Design, Development, and Delivery)
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Open AccessArticle
Do Family Physicians’ Recommendations for Influenza and Pneumococcal Vaccines Impact the Elderly Aged ≥60 Years? A Cross-Sectional Study in Six Chinese Cities
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Yuxing Wang, Jianing Dai, Shuai Yuan, Ying Chen, Zhujiazi Zhang, Ling Zhu, Gang Liu, Qiang Zeng, Qian Qiu, Chunyu Luo, Rendan Deng and Lili You
Vaccines 2025, 13(8), 886; https://doi.org/10.3390/vaccines13080886 - 21 Aug 2025
Abstract
Background: Influenza vaccine and pneumococcal vaccine are essential to protect the health of older adults. This study focuses on the impact of family physicians’ recommendations on influenza and pneumococcal vaccine uptake among urban Chinese older adults and makes recommendations for improving vaccination
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Background: Influenza vaccine and pneumococcal vaccine are essential to protect the health of older adults. This study focuses on the impact of family physicians’ recommendations on influenza and pneumococcal vaccine uptake among urban Chinese older adults and makes recommendations for improving vaccination rates. Methods: A cross-sectional survey on influenza vaccination and pneumonia vaccination was conducted in December 2024 in six cities in China among adults aged ≥60 years. Marginal effects as well as logistic regression models were adopted to measure the relationship between family physician recommendation and influenza vaccination and pneumonia vaccination. Results: The overall influenza vaccination rate was 34.05% and pneumococcal vaccination rate was 22.79%. City, educational level, monthly income, health status, and family physician vaccination recommendation had significant impacts on influenza and pneumococcal vaccination (p < 0.05). Among the investigated elderly population, 48.78% and 28.56% had received recommendations from family physicians regarding influenza and pneumococcal vaccination, respectively. Analysis of marginal effects models revealed that physicians’ recommendations were significantly able to boost influenza and pneumococcal vaccination rates by 26.3% (average marginal effect = 0.263, 95% CI = 0.249–0.277) and 23.7% (average marginal effect = 0.237, 95% CI = 0.225–0.248), respectively (p < 0.001). In the adjusted model, family physician recommendation, compared with no family physician recommendation, was also associated with vaccine policy, monthly income, and age in influenza vaccine and pneumococcal vaccine uptake. Conclusions: Older adults’ influenza and pneumococcal vaccination rates need to be improved. Family physicians’ recommendations show a more significant impact on older adults. Family physician recommendations had the greatest boosting effect on vaccination among individuals aged 70–79. Healthcare providers should adopt different vaccine recommendation strategies based on the characteristics of older adults.
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(This article belongs to the Section Vaccines and Public Health)
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A Phase II Random, Double-Blind, Placebo-Controlled Study of the Safety and Immunogenicity of a Recombinant G Protein-Based Respiratory Syncytial Virus Vaccine in Healthy Older Adults
by
Lunan Zhang, Gan Zhao, Xin Cheng, Shuo Wang, Jiarong Wang, Xuefen Huai, Yu Xia, Yanling Xiao, Sulin Ren, Shijie Zhang, Qiao Wang and Bin Wang
Vaccines 2025, 13(8), 885; https://doi.org/10.3390/vaccines13080885 - 21 Aug 2025
Abstract
Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine,
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Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine, has shown promise in preclinical and Phase 1 studies. This phase II trial sought to determine whether escalating doses of BARS13 could enhance immune responses while maintaining safety and tolerability in healthy older adults aged 60–80 years. Methods: This study employed a rigorous randomized, double-blind, placebo-controlled design involving 125 participants across two Australian centers. Participants were randomized in a 3:1 (vaccine–placebo) ratio for Cohorts 1–2 (30 active, 10 placebo each) and a 2:1 ratio for Cohort 3 (30 active, 15 placebo). Cohort 1 (low dose) received 10 µg rRSV-G + 10 µg CsA in one arm + a placebo in the other (Days 1 and 29); Cohort 2 (high dose) received 10 µg rRSV-G + 10 µg CsA in both arms (20 µg total per dose, Days 1 and 29); Cohort 3 (multi-dose) received the same dose as that of Cohort 2 but with a third dose on Day 57. The placebo groups received IM injections in both arms at matching timepoints. The primary endpoints included safety and tolerability assessments, while the secondary endpoints evaluated the RSV G protein-specific IgG antibody concentrations using enzyme-linked immunosorbent assays (ELISAs). Statistical analysis was performed on both the safety and immunogenicity populations. Results: BARS13 was well-tolerated across all cohorts, with no serious adverse events (SAEs) related to the vaccine. The most common adverse events were mild local reactions (pain and tenderness) and systemic reactions (headache and fatigue), which resolved within 24–48 h. Immunogenicity analysis demonstrated a dose-dependent increase in the RSV G protein-specific IgG geometric mean concentrations (GMCs). Cohort 3, which received multiple high-repeat dose administrations, showed the highest immune response, with the IgG GMC rising from 1195.4 IU/mL on Day 1 to 1681.5 IU/mL on Day 113. Response rates were also the highest in Cohort 3, with 86.2% of participants showing an increase in antibody levels by Day 29. Conclusions: BARS13 demonstrated a favorable safety profile and strong immunogenicity in elderly participants, with a clear dose-dependent antibody response. These results support further development of BARS13 as a potential RSV vaccine candidate for the elderly. Further studies are needed to evaluate the long-term efficacy and optimal dosing schedule.
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(This article belongs to the Special Issue Clinical Strategies to Improve Efficacy, Effectiveness, and Safety of Vaccination in Humans)
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Open AccessArticle
Participation in a Voluntary Blood Donation Program as an Opportunity to Assess and Enhance Tetanus Immunity in Adult Blood Donors with an Outdated or Unknown Vaccination Status
by
Katarzyna Tkaczyszyn, Małgorzata Szymczyk-Nużka and Leszek Szenborn
Vaccines 2025, 13(8), 884; https://doi.org/10.3390/vaccines13080884 - 21 Aug 2025
Abstract
Background/Objectives: Booster vaccination coverage in the adult population in Poland remains insufficient. The objective of this study was to utilize the opportunity of a visit to the Regional Blood Transfusion Center in Wroclaw—associated with blood donation—as a means to remind individuals about the
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Background/Objectives: Booster vaccination coverage in the adult population in Poland remains insufficient. The objective of this study was to utilize the opportunity of a visit to the Regional Blood Transfusion Center in Wroclaw—associated with blood donation—as a means to remind individuals about the need for tetanus booster vaccination and to assess tetanus immunity in healthy adults (30–40 years after their last mandatory dose) who had not received booster immunizations. Materials and Methods: A total of 97 blood donors aged 50 to 64 years (median age: 54 years) were enrolled, of whom 78% were male. 1. Tetanus immunity was assessed by a single measurement of serum anti-tetanus IgG antibody concentration. 2. A questionnaire was used to collect data relevant to tetanus immune status. 3. Individuals with insufficient protection received a booster dose of the tetanus vaccine, and the post-vaccination serologic response was evaluated. Results: 1. In the study group, 10.3% of participants had no protective immunity against Clostridium tetani, while 5.2% exhibited uncertain protection. An additional 32% demonstrated antibody levels conferring only short-term protection. Satisfactory protection—defined as immunity lasting at least 3 years—or long-term protection (at least 5 years) was identified in 52.5% of patients. Although 72% of donors reported receiving mandatory childhood immunizations, only 5% could provide medical documentation. In this subgroup, a significantly higher geometric mean antibody concentration was observed (0.69 vs. 0.52 IU/mL; p = 0.04), and significantly fewer participants required immediate post-exposure prophylaxis (1/39 vs. 14/54; p = 0.003). 2. Among the 46 individuals eligible for a booster dose, 17 (37%) returned for vaccination. Of these, 16 (94%) achieved antibody titers consistent with long-term protection following a single vaccine dose. Conclusions: Tetanus immunity among adults is heterogeneous and difficult to predict due to the frequent lack of vaccination records and unreliable self-reported histories. A history of injury and associated surgical wound care involving injection often serves as the only indication of prior vaccination. A single booster dose is highly effective in eliciting a robust immune response in individuals vaccinated during childhood but lacking recent boosters. Rising vaccine hesitancy toward both mandatory and recommended immunizations in Poland negatively influences adult decisions regarding tetanus vaccination. Participation in voluntary blood donation programs presents a valuable opportunity for immunization education, immune status screening, and the implementation of effective catch-up vaccination strategies.
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(This article belongs to the Section Vaccines and Public Health)
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Open AccessArticle
Immunogenic and Protective Properties of mRNA Vaccine Encoding Hemagglutinin of Avian Influenza A/H5N8 Virus, Delivered by Lipid Nanoparticles and Needle-Free Jet Injection
by
Vladimir A. Yakovlev, Victoria R. Litvinova, Nadezhda B. Rudometova, Mariya B. Borgoyakova, Elena V. Tigeeva, Ekaterina V. Starostina, Ksenia I. Ivanova, Andrei S. Gudymo, Natalia V. Danilchenko, Olga N. Perfilyeva, Kristina P. Makarova, Danil I. Vahitov, Boris N. Zaitsev, Elena V. Dmitrienko, Sergey V. Sharabrin, Svetlana I. Krasnikova, Lyubov A. Kisakova, Denis N. Kisakov, Tatiana N. Ilyicheva, Vasiliy Yu. Marchenko, Larisa I. Karpenko, Andrey P. Rudometov and Alexander A. Ilyichevadd
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Vaccines 2025, 13(8), 883; https://doi.org/10.3390/vaccines13080883 - 21 Aug 2025
Abstract
Background/Objectives: The development of a vaccine against highly pathogenic avian influenza viruses subtype A/H5 is an urgent task due to concerns about its pandemic potential. Methods: In this study, we have developed an experimental mRNA vaccine, mRNA-H5, encoding a modified hemagglutinin trimer of influenza
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Background/Objectives: The development of a vaccine against highly pathogenic avian influenza viruses subtype A/H5 is an urgent task due to concerns about its pandemic potential. Methods: In this study, we have developed an experimental mRNA vaccine, mRNA-H5, encoding a modified hemagglutinin trimer of influenza virus A/turkey/Stavropol/320-01/2020 (H5N8). BALB/c mice were immunized with the mRNA-H5 vaccine using lipid nanoparticles (LNPs) and needle-free jet injection (JI). Subsequently, the immune response to vaccine was assessed using ELISA, microneutralization assay, and ICS methods, and a challenge study was conducted. Results: mRNA-H5 was shown to effectively stimulate specific humoral and T-cell immune responses. Moreover, mRNA-H5 delivered by LNPs and JI provided 100% protection of immunized mice against lethal challenge with homologous and heterologous strains of avian influenza virus (A/Astrakhan/3212/2020 (H5N8) and A/chicken/Magadan/14-7V/2022 (H5N1), respectively). Conclusions: The present results indicate that JI can be considered as an alternative to LNPs for mRNA delivery, and according to the literature, JI is safer than delivery using LNP. mRNA-H5 has potential as a vaccine against infection with highly pathogenic avian influenza A/H5 viruses with pandemic potential.
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(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)
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Open AccessReview
Decrypting the Immune Symphony for RNA Vaccines
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Brian Weidensee and Itishri Sahu
Vaccines 2025, 13(8), 882; https://doi.org/10.3390/vaccines13080882 - 20 Aug 2025
Abstract
Messenger RNA (mRNA) vaccine technology has revolutionized the field of immunization, offering a non-infectious, non-genome-integrating platform that addresses many limitations of traditional vaccine modalities. Recent advancements in chemical modifications, delivery systems, and manufacturing processes have enhanced the stability, efficacy, and safety of RNA-based
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Messenger RNA (mRNA) vaccine technology has revolutionized the field of immunization, offering a non-infectious, non-genome-integrating platform that addresses many limitations of traditional vaccine modalities. Recent advancements in chemical modifications, delivery systems, and manufacturing processes have enhanced the stability, efficacy, and safety of RNA-based therapeutics, expanding their application beyond infectious diseases to include genetic disorders, cancer, and rare diseases. Central to the success of RNA vaccines is their ability to orchestrate a finely tuned immune response, leveraging both innate and adaptive immunity to achieve robust and durable protection. This review synthesizes current knowledge on the immunological mechanisms underpinning RNA vaccine efficacy, with a focus on the roles of pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) in sensing exogenous RNA, the impact of RNA modifications and manufacturing impurities on innate immune activation, and the subsequent cytokine and chemokine milieu that shapes adaptive responses. We also discuss the dual role of lipid nanoparticle (LNP) delivery systems as both carriers and adjuvants, highlighting their contribution to the vaccine’s immunogenicity and reactogenicity profile. Understanding these complex immune interactions is critical for optimizing RNA vaccine design, minimizing adverse effects, and expanding their therapeutic potential. This review aims to provide a comprehensive overview of the immune symphony orchestrated by RNA vaccines and to identify key areas for future research to further refine and expand the utility of this transformative technology.
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(This article belongs to the Special Issue Evaluating the Immune Response to RNA Vaccine)
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Open AccessReview
Therapeutic Vaccines for Non-Communicable Diseases: Global Progress and China’s Deployment Pathways
by
Yifan Huang, Xiaohang Lyu and Yiu-Wing Kam
Vaccines 2025, 13(8), 881; https://doi.org/10.3390/vaccines13080881 - 20 Aug 2025
Abstract
Background: Non-communicable diseases (NCDs) have become a major threat to global public health, with the disease burden particularly severe in developing countries, China being one of them. The preventive and control effects of traditional treatment methods on NCDs are limited, and innovative strategies
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Background: Non-communicable diseases (NCDs) have become a major threat to global public health, with the disease burden particularly severe in developing countries, China being one of them. The preventive and control effects of traditional treatment methods on NCDs are limited, and innovative strategies are urgently needed. In recent years, vaccine technology has expanded from the field of infectious diseases to non-communicable diseases (NCDs). Therapeutic vaccines have shown the potential to intervene in chronic diseases through immunomodulation, but their research and development (R & D), as well as promotion, still face multiple challenges. Methods: This article systematically reviews the current development status of NCD vaccines worldwide and points out the imbalance in their matching with disease burden: current research focuses on the field of cancer, while there is a lack of targeted vaccines for high-burden diseases such as hypertension and chronic kidney disease; the progress of independent R & D in China lags behind, and there are implementation obstacles such as uneven distribution of medical resources between urban and rural areas and low public willingness to be vaccinated. Results: By analyzing the biological mechanisms of NCD vaccines and non-biological challenges, phased solutions are proposed: In the short term, focus on target discovery and improvement of vaccine accessibility. In the medium term, strengthen multi-center clinical trials and international technology sharing. In the long term, build a digital health monitoring system and a public–private partnership financing model. Conclusions: The breakthrough of NCD vaccines requires interdisciplinary collaboration and systematic policy support. Their successful application will reshape the paradigm of chronic disease prevention and control, providing a new path for global health equity.
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(This article belongs to the Special Issue Virus Pandemics and Vaccinations)
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Oncolytic Herpes Simplex Virus Therapy: Latest Advances, Core Challenges, and Future Outlook
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Yiyang Zheng, Yusheng Pei, Chunyan Dong, Jinghui Liang, Tong Cai, Yuan Zhang, Dejiang Tan, Junzhi Wang and Qing He
Vaccines 2025, 13(8), 880; https://doi.org/10.3390/vaccines13080880 - 20 Aug 2025
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Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval
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Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies.
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Development and Biological Properties of a New Live Attenuated Mumps Vaccine Strain
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Xue Song, Xiumei Ren, Yang Song, Shengbao Yang, Kailang Lu, Yan Zhang and Jiankai Liu
Vaccines 2025, 13(8), 879; https://doi.org/10.3390/vaccines13080879 - 20 Aug 2025
Abstract
Background/Objectives: This study aimed to develop a new attenuated live mumps vaccine strain and determine its biological properties and effectiveness. Methods: Plaque purification and amplification were performed in chicken embryo cells. Candidate live attenuated mumps MuV-365 strain sequencing was performed. After
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Background/Objectives: This study aimed to develop a new attenuated live mumps vaccine strain and determine its biological properties and effectiveness. Methods: Plaque purification and amplification were performed in chicken embryo cells. Candidate live attenuated mumps MuV-365 strain sequencing was performed. After evaluating the potential neurotoxicity of the MuV-365 mumps strain, a preclinical safety evaluation of measles–mumps–rubella (MMR) live attenuated vaccine containing the MuV-365 strain was performed to support the registration and application of the MMR vaccine. Finally, mumps neutralization antibody titers and the concentration of anti-serum mumps-specific IgG were determined to evaluate the immunogenicity and efficacy of the MuV-365 strain and MMR vaccine in mice and rhesus monkeys. Results: The plaque of the PL-KUM main seed virus was screened, and strains whose sequences were highly homologous to RIT4385 (JL-5 derived) were selected to amplify. The candidate live attenuated mumps MuV-365 strain was then developed. Safety evaluation results indicated that the MuV-365 strain had no potential neurotoxicity, and the MMR vaccine containing the MuV-365 strain also showed no significant safety hazard. The immunogenicity of MuV-365 strain in BALB/c mice was not inferior to S79 and PL-KUM. After two doses of the MuV-365 strain, the concentration of anti-serum mumps-specific IgG of the MuV-365 strain was significantly higher than that of the S79 strain (p < 0.01). In rhesus monkeys, the MMR vaccine had good immunogenicity against measles and rubella after one dose, while immunogenicity against mumps improved after two doses. Conclusions: The developed MuV-365 strain was genetically stable, with adequate safety and immunogenicity.
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(This article belongs to the Special Issue Advancements in Vaccine Research: Epidemiology, Immunogenicity, Effectiveness and Safety)
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Correction: Riccò et al. Respiratory Syncytial Virus: A WAidid Consensus Document on New Preventive Options. Vaccines 2024, 12, 1317
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Matteo Riccò, Bahaa Abu-Raya, Giancarlo Icardi, Vana Spoulou, David Greenberg, Oana Falup Pecurariu, Ivan Fan-Ngai Hung, Albert Osterhaus, Vittorio Sambri and Susanna Esposito
Vaccines 2025, 13(8), 878; https://doi.org/10.3390/vaccines13080878 - 20 Aug 2025
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The authors would like to make the following corrections to this published paper [...]
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Open AccessArticle
Trends in DTP3 Vaccination in Asia (2012–2023)
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Ines Aguinaga-Ontoso, Laura Guillen-Aguinaga, Sara Guillen-Aguinaga, Rosa Alas-Brun, Miriam Guillen-Aguinaga, Enrique Aguinaga-Ontoso, Luc Onambele and Francisco Guillen-Grima
Vaccines 2025, 13(8), 877; https://doi.org/10.3390/vaccines13080877 - 19 Aug 2025
Abstract
Background/Objectives: DTP3 (diphtheria–tetanus–pertussis vaccine, third dose) coverage is a key indicator of the strength and continuity of routine immunization programs, which demonstrably reduces the burden of infectious diseases globally. This study aims to assess trends in DTP3 vaccination coverage across Asian regions and
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Background/Objectives: DTP3 (diphtheria–tetanus–pertussis vaccine, third dose) coverage is a key indicator of the strength and continuity of routine immunization programs, which demonstrably reduces the burden of infectious diseases globally. This study aims to assess trends in DTP3 vaccination coverage across Asian regions and countries from 2012 to 2023, focusing on changes associated with the COVID-19 pandemic. Methods: DTP3 vaccination data were obtained from official WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) and analyzed using Joinpoint regression to detect statistically significant changes in vaccination trends. Data were grouped by five Asian subregions based on the UN geoscheme (Central, Eastern, Southeastern, Southern, and Western Asia), and trends were weighted using birth cohort sizes. The presence of joinpoints and annual percentage changes (APCs) was calculated, and potential pandemic-related disruptions were contextualized. Results: At the continental level, Asia experienced a modest 0.4% annual increase in DTP3 coverage between 2012 and 2023, with a significant joinpoint detected in 2018. Following this, Southeast Asia’s coverage declined at an annual rate of −4.32% before beginning to recover in 2021, while South Asia showed a similar pattern. Country-level analysis revealed significant heterogeneity, with a comparison between 2019 and 2023 showing profound post-pandemic declines in some nations, such as Lebanon (–21%) and Myanmar (–9.4%), while others, like Iraq and the Philippines, achieved substantial recoveries with coverage increasing by over 6 percentage points. These trends contrasted with persistent declines in fragile states (e.g., Afghanistan, Yemen) and sustained high coverage in others (e.g., Bangladesh, Israel). The pandemic, systemic weaknesses, emerging vaccine hesitancy, and misinformation were identified as key influences. Conclusions: There is progress in DTP3 coverage across Asia. There were pandemic-related disruptions, particularly in regions with fragile health systems. Strategies to address zero-dose and dropout children, improve service continuity, and counter misinformation are essential to meet immunization targets under the Immunization Agenda 2030.
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(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)
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BCG Vaccine-Induced Innate and Adaptive Pulmonary Immunity Correlating with Protective Efficacy Against Mycobacterium tuberculosis in the Lungs
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Mayank Khanna and Alistair J. Ramsay
Vaccines 2025, 13(8), 876; https://doi.org/10.3390/vaccines13080876 - 19 Aug 2025
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Background/Objectives: Effective prophylaxis for Mycobacterium tuberculosis (Mtb) requires greater understanding of immune correlates of protection. With renewed interest in BCG as an Mtb vaccine, particularly via the intravenous (IV) route, our objective was to characterize both innate and adaptive immune correlates of vaccine-induced
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Background/Objectives: Effective prophylaxis for Mycobacterium tuberculosis (Mtb) requires greater understanding of immune correlates of protection. With renewed interest in BCG as an Mtb vaccine, particularly via the intravenous (IV) route, our objective was to characterize both innate and adaptive immune correlates of vaccine-induced pulmonary immunity as potential biomarkers for protective efficacy in a murine model of Mtb infection. Methods: Mice were given BCG via different routes and some boosted with recombinant virus constructs encoding Mtb Ag85B. Responding innate lymphoid cell (ILC) populations, T cells and B cells were analyzed by fluorescence activated cell sorting (FACS) for surface markers and by intracellular cytokine staining or antibody ELISPOT. Some immunized mice were challenged with aerosolized Mtb and monitored for bacterial growth in the lungs and spleen. Results: BCG given IV, but not intranasally or subcutaneously, resulted in marked increases in IFNγ expression at 72 h by pulmonary CD49+ NK cells, CD69+ ILC1, and two ILC3 populations, NCR-ILC3 and LTi cells, the latter also producing IL-22. Pulmonary ILC2 populations in these mice had significantly increased IL-13 expression at 24 h compared to the other routes. Interestingly, high levels of NK cells and ILC1 expressing IFNγ and/or TNFα were sustained at 8 wk, with sustained expression of IL-17A by pulmonary NCR-ILC3 and pronounced tissue-resident and effector memory CD4+ and CD8+ T cell responses. Intranasal boosting with Ad-Ag85B enhanced these T cell responses and generated Mtb-specific pulmonary IgA and IgG B cells, correlating with significantly reduced bacterial loads following Mtb challenge. Conclusions: BCG given IV primed for both early and persistent pulmonary ILC1/ILC3 responses of a predominantly Th1/Th17-type profile along with local Mtb-specific memory T cell and B cell populations, correlating with enhanced protective efficacy. These are worthy of further study as compartmentalized biomarkers for effective vaccine-induced local immunity against Mtb.
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Putting the Polio Workforce to Work in a Public Health Crisis: Contributions of the National Stop Transmission of Polio (NSTOP) Program to the COVID-19 Response in Pakistan
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Aslam Pervaiz, Rana Muhammad Safdar, Mumtaz Ali Laghari, Nadeem Shah, Amjad Mehmood, Kifayat Ullah, Richard Franka and Chukwuma Mbaeyi
Vaccines 2025, 13(8), 875; https://doi.org/10.3390/vaccines13080875 - 19 Aug 2025
Abstract
Background: Pakistan reported its first case of COVID-19 in February 2020 and joined other countries in activating a national emergency response following the declaration of the COVID-19 pandemic by the World Health Organization (WHO). Playing a vital role in the early phase
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Background: Pakistan reported its first case of COVID-19 in February 2020 and joined other countries in activating a national emergency response following the declaration of the COVID-19 pandemic by the World Health Organization (WHO). Playing a vital role in the early phase of the country’s response was the National Stop Transmission of Polio (NSTOP) program, a highly trained cadre of polio workers who ordinarily support polio eradication efforts in the country. Methods: We developed a reporting tool using Microsoft Excel that tracked the activities of NSTOP officers to support the COVID-19 response. All NSTOP officers submitted their activity reports fortnightly using this reporting tool. Each provincial NSTOP officer reviewed and compiled their respective officers’ reports and sent them to the federal NSTOP Team. We present a summary of the reports for the period from 1 March 2020 to 31 July 2020. Results: A total of 71 officers of the NSTOP program supported various aspects of Pakistan’s COVID-19 response, including coordination, detection and response activities, surveillance, quarantine/isolation management, training and orientation sessions for healthcare personnel, data analysis, community engagement, and risk communication. They successfully investigated 32,729 suspected COVID-19 cases, of which about one-third were confirmed cases, and facilitated the collection and dispatch of >57,000 samples from these cases. Conclusions: This report details NSTOP contributions to the early phase of the COVID-19 response in Pakistan, demonstrating the value of polio investments beyond eradicating the disease to encompass having a workforce that is ready to respond to emergent disease threats and outbreaks. Such a workforce could also play a role in strengthening the capacity of existing immunization systems to help improve routine vaccination coverage in resource-limited settings.
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(This article belongs to the Special Issue Vaccines and Vaccinations in the Pandemic Period)
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Exploring TREC and KREC Levels in Nursing Home Residents and Staff and Their Association with SARS-CoV-2 Antibody Response After Vaccination
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Eline Meyers, Natalja Van Biesen, Liselore De Rop, Tine De Burghgraeve, Marina Digregorio, Laëtitia Buret, Samuel Coenen, Beatrice Scholtes, Jan Y. Verbakel, Stefan Heytens and Piet Cools
Vaccines 2025, 13(8), 874; https://doi.org/10.3390/vaccines13080874 - 19 Aug 2025
Abstract
Background: T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are markers of recent thymic and bone marrow output, respectively. As they have previously been associated with immunosenescence, we aimed to investigate their association with anti-spike SARS-CoV-2 (S1RBD) IgG antibody response
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Background: T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are markers of recent thymic and bone marrow output, respectively. As they have previously been associated with immunosenescence, we aimed to investigate their association with anti-spike SARS-CoV-2 (S1RBD) IgG antibody response after COVID-19 vaccination in nursing home residents (NHRs) and staff (NHS). Methods: We measured TREC and KREC levels and S1RBD IgG antibody levels from dried blood spots (DBSs) using in-house qPCRs and a commercial ELISA kit, respectively, in 200 participants (50 NHRs and 150 NHS). DBSs were collected in April 2021, approximately two months after primary course COVID-19 vaccination (BNT162b2). We assessed the association between TREC and KREC as dependent variables and age, sex, infection-priming status, and post-vaccination S1RBD-specific IgG concentrations as independent variables by simple and multiple linear regression. Results: TREC and KREC levels were significantly lower in NHRs compared with NHS and were negatively correlated with age (p < 0.001). Neither TREC nor KREC levels were significantly associated with SARS-CoV-2 antibody concentrations (p > 0.05). Conclusions: In our study population, TREC and KREC levels decreased with age and were statistically significantly lower in NHRs than NHS. They were, however, not associated with the antibody response after COVID-19 vaccination. Yet, additional research is warranted to explore their potential relevance in cellular immune responses or in combination with other biomarkers of immune function.
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(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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IgG Antibodies to Pneumococcal Serotypes 1 and 5 in Relation to PCV13 Vaccination Status in Children Aged Under 5 Years in Lao PDR: A Cross-Sectional Survey
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Zheng Quan Toh, Ke Xin Tang, Keoudomphone Vilivong, Jana Lai, Toukta Bounkhoun, Valin Chanthaluanglath, Anisone Chanthongthip, Anne Balloch, Paul N. Newton, Audrey Dubot-Pérès, David A. B. Dance, Paul V. Licciardi and Fiona M. Russell
Vaccines 2025, 13(8), 873; https://doi.org/10.3390/vaccines13080873 - 18 Aug 2025
Abstract
Background/Objectives: Pneumococcal serotypes 1 and 5 are associated with invasive pneumococcal disease (IPD). However, data on the circulation of these serotypes in Asia following the introduction of the pneumococcal conjugate vaccine (PCV) is limited. The Lao People’s Democratic Republic (Lao PDR) introduced PCV13
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Background/Objectives: Pneumococcal serotypes 1 and 5 are associated with invasive pneumococcal disease (IPD). However, data on the circulation of these serotypes in Asia following the introduction of the pneumococcal conjugate vaccine (PCV) is limited. The Lao People’s Democratic Republic (Lao PDR) introduced PCV13 into its national immunisation programme in 2013. We undertook a serosurvey to assess the IgG responses to serotypes 1 and 5 from a convenience sample of children aged under 5 years in Vientiane, Lao PDR. Methods: This cross-sectional analysis used a convenience sample of the close contacts of children under five years old who had been hospitalised with acute respiratory infections between 2013 and 2016 in Vientiane, Lao PDR. Serotype-specific IgG concentrations to serotypes 1 and 5 were measured using a modified WHO ELISA method. Results: A total of 214 participants were included, 130 of whom were unvaccinated and 84 were vaccinated with PCV13. Compared to unvaccinated participants, a higher number of PCV-vaccinated participants met the IgG threshold for IPD (≥0.35 μg/mL) [41.5% (54/130) vs. 71.4% (60/84)] for serotype 1. In contrast, for serotype 5, a similar number of participants in the PCV-vaccinated and unvaccinated group met the IgG threshold for IPD (85.7% (72/84) vs. 82.3% (107/130). Among unvaccinated children, serotype 1 IgG levels peaked at 12 and 23 months at 0.49 µg/mL (95% CIs: 0.25–0.96), while serotype 5 IgG levels were similar across age groups, ranging from 0.55 to 0.79 µg/mL. Conclusions: Our findings indicate the considerable circulation of serotypes 1 and 5 within the community in Lao PDR. Ongoing surveillance is important for informing PCV vaccination strategies.
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(This article belongs to the Special Issue Host Immunity and Vaccines for Respiratory Pathogens)
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