Journal of Medical Virology最新文献

{"title":"Genomic Epidemiology of the Main SARS-CoV-2 Variants Circulating in Italy During the Omicron Era","authors":"Annalisa Bergna,&nbsp;Alessia Lai,&nbsp;Fabio Sagradi,&nbsp;Stefano Menzo,&nbsp;Nicasio Mancini,&nbsp;Bianca Bruzzone,&nbsp;Stefano Rusconi,&nbsp;Greta Marchegiani,&nbsp;Nicola Clementi,&nbsp;Daniela Francisci,&nbsp;Ilaria Vicenti,&nbsp;Silvia Ronchiadin,&nbsp;Harcel Djaya Mbissam,&nbsp;Carla della Ventura,&nbsp;Leonardo Lanfranchi,&nbsp;Sophie Testa,&nbsp;Sara Caucci,&nbsp;Carla Acciarri,&nbsp;Luca Carioti,&nbsp;Alessandro Occhionero,&nbsp;Federica Novazzi,&nbsp;Angelo Paolo Genoni,&nbsp;Francesca Drago Ferrante,&nbsp;Vanessa De Pace,&nbsp;Monica Ferraris,&nbsp;Matilde Ogliastro,&nbsp;Arianna Gabrieli,&nbsp;Massimo De Paschale,&nbsp;Giada Canavesi,&nbsp;Maria Concetta Bellocchi,&nbsp;Marco Iannetta,&nbsp;Loredana Sarmati,&nbsp;Francesca Ceccherini-Silberstein,&nbsp;Agostino Riva,&nbsp;Spinello Antinori,&nbsp;Gianguglielmo Zehender,&nbsp;SARS-CoV-2 ITALIAN RESEARCH ENTERPRISE – collaborative Group","doi":"10.1002/jmv.70215","DOIUrl":"https://doi.org/10.1002/jmv.70215","url":null,"abstract":"<p>Since early 2022 the Omicron variant has rapidly spread worldwide, becoming the dominant variant to date. The study aimed to investigate the clinical and epidemiological characteristics of COVID-19 patients and reconstruct the genomic epidemiology of main SARS-CoV-2 Omicron sublineages in Italy in 2022. A total of 8970 SARS-CoV-2 samples were studied, and phylogenetic analyses were focused on BA.1, BA.2, and BA.5 subvariants. More than half of subjects received three doses of vaccine and experienced a reinfection. A significant larger proportion of unvaccinated subjects presented reinfection compared with vaccinated. Clusters presented a tMRCA between September–November 2021 (BA.1), November 2021–January 2022 (BA.2), and October 2021–May 2022 (BA.5). <i>R</i>_e values showed the highest level between September–October, January–February 2022, and May 2022 for BA.1, BA.2 and BA.5, respectively. Limited number of studied variant sequences are included in clusters. The spread rate of the studied variant exceeded its evolutionary rate. No single sublineage had sufficient time to differentiate into large clusters, but only into small and fragmented groups sharing the same recent ancestor. These analyses dissect the epidemiological dynamics of Omicron sublineages in Italy over a period of great epidemiological changes in the COVID-19 epidemic.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Threat of Disease X: Preparing for the Next Global Pandemic","authors":"Mengyuan Zhao,&nbsp;Luping Lei,&nbsp;Yinghan Jiang,&nbsp;Yuxin Tian,&nbsp;Yuanyu Huang,&nbsp;Minghui Yang","doi":"10.1002/jmv.70227","DOIUrl":"https://doi.org/10.1002/jmv.70227","url":null,"abstract":"<div>\u0000 \u0000 <p>The term “Disease X”, first introduced by the World Health Organization (WHO) in 2018, symbolizes the threat of an unknown pathogen capable of causing a global pandemic. Classified as a “priority pathogens,” Disease X stands alongside well-known threats like SARS, Ebola, and ZIKV due to its potential for widespread outbreaks. SARS-CoV-2 is considered the first “Disease X” to fulfill this prediction, demonstrating the devastating impact such pathogens can have. A future pathogen X could pose an even greater threat, with catastrophic consequences. This paper examines the potential origins of such pathogens, drawing lessons from outbreaks like SARS, MERS, and SARS-CoV-2. It also highlights strategic approaches to detect, prevent, and respond effectively to mitigate the risk of future pandemics.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of 5A's of Human Papilloma Virus Vaccination: Awareness, Attitude, Apprehension, Action Expected and Acceptability Amongst Health Care Providers, Medical Students, Para-Medical and Administration Staff in AIIMS Rajkot","authors":"Sweta Soni,&nbsp;Sarjil Amin,&nbsp;Ashish Pundhir,&nbsp;Rohini Krishna Ramotra","doi":"10.1002/jmv.70231","DOIUrl":"https://doi.org/10.1002/jmv.70231","url":null,"abstract":"<div>\u0000 \u0000 <p>The study aims to assess awareness, attitude, apprehension, action expected from policy makers, and acceptability towards HPV vaccination amongst health care providers (HCP), medical students, paramedical staff and administrative personnel. A cross-sectional study was conducted with 501 participants, including HCP, medical students, paramedical and administrative staff. Their awareness, attitudes, apprehensions, actions expected from policymakers, and acceptability towards HPV vaccine were assessed through a Google Form survey. Of the 501 participants, 92.4% were aware of HPV vaccines, 24.6% had a thorough understanding of HPV, but only 5.8% had received the vaccine. Most participants held a positive attitude toward cervical cancer prevention and HPV vaccination, although 46.7% expressed apprehensions. Before viewing educational video, 278 participants (55.8%) were willing to receive the HPV vaccine, while 116 (44.2%) were not. After viewing the educational video, willingness increased to 394 participants (78.6%), and those unwilling decreased to 107 (21.4%). Factors such as age, gender, marital status, education, and professional role did not significantly predict knowledge or apprehension regarding HPV and the HPV vaccine. However, professional role and younger adult (20–39 years) groups were statistically significant predictors of a positive attitude as well as stronger expectations for action from policymakers towards HPV vaccine. The study reveals significant gaps in HPV vaccine awareness and uptake among medical professionals, paramedics, and administrative staff. It highlights the need for broad educational programs to address these knowledge gaps, emphasizing HPV's health impacts and preventive measures. Multimedia educational interventions effectively boost vaccine acceptance among the groups and the general public.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Reevaluation of Repurposed Drugs Against the Main Protease of SARS-CoV-2 via Combined Experiments","authors":"Jiankai Ye,&nbsp;Rui Zhang,&nbsp;Jiahao Zhou,&nbsp;Tao Xu,&nbsp;Xiaoping Liu,&nbsp;Yunyu Chen","doi":"10.1002/jmv.70229","DOIUrl":"https://doi.org/10.1002/jmv.70229","url":null,"abstract":"<div>\u0000 \u0000 <p>The main protease (Mpro) of SARS-CoV-2 is an attractive drug target for antivirals, as this enzyme plays a key role in virus replication. Drug repurposing is a promising option for the treatment of coronavirus disease 2019 (COVID-19). Recently, a number of FDA-approved drugs have been identified as Mpro inhibitors, but stringent hit validation is lacking. In this study, we rigorously reevaluated the in vitro inhibition of the Mpro enzyme by repurposed drugs via combined experiments, including the fluorescence resonance energy transfer (FRET) assay, fluorescence polarization (FP) assay, and protease biosensor cleavage assay. Our results from a set of in vitro assays revealed that boceprevir is a potential Mpro inhibitor, but other repurposed drugs, including atazanavir, dipyridamole, entrectinib, ethacridine, glecaprevir, hydroxychloroquine, ivermectin, meisoindigo, pelitinib, raloxifene, roxatidine acetate, saquinavir, teicoplanin, thonzonium bromide, and valacyclovir, are not. Our research highlights that the use of candidate Mpro inhibitors from primary screening warrants further comprehensive studies before the reporting of new findings.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Impact and Genetic Analysis of Enteric Viruses Associated With Acute Gastroenteritis in Greater Accra, Ghana: A Comprehensive Study of Five Viruses","authors":"Lawrence Henry Ofosu-Appiah,&nbsp;Manami Negoro,&nbsp;Jennifer Xolali Amexo,&nbsp;Dodzi Kofi Amelor,&nbsp;Prince Baffour Tonto,&nbsp;Dennis Odai Laryea,&nbsp;Keiko Yamasaki,&nbsp;Franklin Asiedu-Bekoe,&nbsp;Ken Sugata,&nbsp;Hiroki Hori,&nbsp;Narufumi Suganuma,&nbsp;Kiyosu Taniguchi","doi":"10.1002/jmv.70216","DOIUrl":"https://doi.org/10.1002/jmv.70216","url":null,"abstract":"<div>\u0000 \u0000 <p>Enteric viruses are significantly associated with acute gastroenteritis globally. Despite a decrease in severe rotavirus associated diarrhoea, Ghana still records high diarrhoea burden. Meanwhile aetiological investigations in hospital settings do not routinely include viral testing. Rotavirus vaccination is thought to alter enteric viral populations and impact evolution. To better understand virus-specific effects in acute gastroenteritis in both children and adults, we tested fecal samples from 228 patients at two hospitals in Accra from January to December 2019, using multiplex and singleplex PCR assays. The clinical impact of detected viruses was assessed using a modified Vesikari score system. Partial viral genome sequences were obtained by Sanger Sequencing and their genetic diversity and evolutionary history, traced by phylogenetic analyses. At least one enteric virus was found in 86 (37.7%) patient samples, with 36.9% of the population under five infected. Single infections of rotavirus, norovirus, adenovirus, sapovirus and astrovirus were 33, 14, 8, 6, and 1, respectively, while coinfections were 24. Rotavirus accounted for 33.3% of 24 clinically severe cases (modified Vesikari score &gt; 7). Three out of 10 rotavirus cases with evidence of vaccination experienced severe gastroenteritis. Diverse genotypes, including RVA G2P[4], G1P[8], G12P[8] and G12P[6]; AdV F40 and F41; NoV GII.4 Sydney 2012, GII.6 and GI.3, several of which clustered with contemporary strains from the Americas, Europe and Asia, were detected. This study also provides the first report of SaV GI.1, GI.7 and GII.8 detection in humans in Ghana. RVA G2P[4] and AdV F were associated with higher proportions of hospitalizations. While RVA continues to have a profound clinical impact on gastroenteritis, AdV and SaV produce an equally severe disease. In contrast, NoV and AstV showed a generally mild to moderate impact on clinical disease severity.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity and Efficacy of an Accelerated Vaccination Schedule Against Hepatitis E Virus Infection in Rabbits","authors":"Fan Zhang,&nbsp;Zuliang Shi,&nbsp;Yihan Wu,&nbsp;Jianbo Xia,&nbsp;Ling Wang","doi":"10.1002/jmv.70218","DOIUrl":"https://doi.org/10.1002/jmv.70218","url":null,"abstract":"<div>\u0000 \u0000 <p>An important goal of the hepatitis E virus (HEV) vaccine is to prevent HEV in fragile, conflict-affected, and vulnerable (FCV) settings with documented HEV circulation, but the routine hepatitis E vaccination schedule (0, 1, and 6 months) might not provide adequate protection for them in time. Therefore, in this study, we aimed to evaluate the immunogenicity and efficacy of a HEV vaccine (HEV 239 vaccine, Hecolin) using an accelerated vaccination schedule (vaccine doses at 0 and 7 days). Two doses of accelerated vaccination schedule (0 and 7 days) induced high titers of anti-HEV protective antibodies in a short period of time in rabbits of the vaccine group, which could protect the rabbits from HEV infection compared with the infection group. Our results suggest that an accelerated vaccination schedule (0 and 7 days) could provide protective antibodies in a shorter time. The accelerated schedule should be further recommended for use as a backup in FCV settings or during a hepatitis E outbreak.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Fullerene (C60 & C70)-Meso-Tris-4-Carboxyphenyl Porphyrin Dyads Inhibit Entry of Wild-Type and Drug-Resistant HIV-1 Clades B and C”","authors":"","doi":"10.1002/jmv.70232","DOIUrl":"https://doi.org/10.1002/jmv.70232","url":null,"abstract":"<p>D. Sharma, M. Rai, A. Singh, R. Gaur, and D. Senguptaa, “Fullerene (C60 &amp; C70)-Meso-Tris-4-Carboxyphenyl Porphyrin Dyads Inhibit Entry of Wild-Type and Drug-Resistant HIV-1 Clades B and C,” <i>Journal of Medical Virology</i> 97 (2025): e70181, https://doi.org/10.1002/jmv.70181.</p><p>In the originally published article, the family name of the corresponding author, Devashish Sengupta, was incorrectly spelled as “Senguptaa.” This has now been corrected to “Devashish Sengupta.”</p><p>We apologize for this error.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Novel Oncolytic Herpes Simplex Virus Type-1 (HSV-1) Vaccine Strain VC2 Constitutively Expressing GM-CSF Causes Increased Intratumoral T Cell Infiltration and Inhibition of Tumor Metastasis in the 4T1/Balb/c Mouse Model of Stage Four Breast Cancer","authors":"Rafiq Nabi,&nbsp;Vladimir N. Chouljenko,&nbsp;Farhana Musarrat,&nbsp;Megan E. Davis,&nbsp;Harikrishnan Mohan,&nbsp;Reza Ghavimi,&nbsp;Brent Stanfield,&nbsp;Ojasvi Dutta,&nbsp;Konstantin G. Kousoulas","doi":"10.1002/jmv.70220","DOIUrl":"https://doi.org/10.1002/jmv.70220","url":null,"abstract":"<div>\u0000 \u0000 <p>Oncolytic virotherapy (OVT) aims to disrupt the tumor microenvironment and provide a unique therapeutic approach against solid tumors. Herpes simplex virus type-1 (HSV-1) has shown strong promise for treating various solid tumors and has been approved to treat melanoma and glioma in human patients. Previously, we reported the generation of an engineered HSV-1 vaccine strain VC2, which has shown exceptional promise as an oncolytic and immunotherapeutic virus. In the present work, we engineered VC2 to constitutively express the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) gene inserted in place of HSV-1 Glycoprotein C (gC). We tested the efficacy of VC2-GMCSF for its ability to generate antitumor response in the 4T1 stage four metastatic breast cancer mouse model. GM-CSF expression enhanced VC2 viral replication and infectious virus production. Tumors formed after 7 days of engraftment in the mammary fat pad of Balb/CJ mice were treated by injecting ~5 × 10⁴ plaque forming units (PFU) of VC2/VC2-GMCSF once. Intratumor treatment did not appreciably reduce average primary tumor sizes. However, metastatic foci were significantly reduced in mice lungs treated with VC2-GMCSF compared to VC2 or mock treatment. VC2-GMCSF intratumoral treatment induced a stronger intratumor T cell infiltration but not an increased cytotoxic activity. A significant T cell infiltration was observed in the metastatic areas in VC2-GMCSF treated animals, which was associated with reduced pro-tumor marker PDL1 and VEGF gene expression. These results show that constitutive expression of GM-CSF enhanced the overall efficacy of VC2 for OVT. VC2-GMCSF holds promise as oncolytic and immunotherapeutic virotherapy for breast and other cancers.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Discovery of a Therapeutic Lead for HFMD From a Library Screen of Rocaglates/Aglains","authors":"Adrian Oo,&nbsp;Angel Borge,&nbsp;Regina Ching Hua Lee,&nbsp;Cyrill Kafi Salim,&nbsp;Wenyu Wang,&nbsp;Michael Ricca,&nbsp;Deborah Yuhui Fong,&nbsp;Sylvie Alonso,&nbsp;Lauren E. Brown,&nbsp;John A. Porco Jr.,&nbsp;Justin Jang Hann Chu","doi":"10.1002/jmv.70228","DOIUrl":"https://doi.org/10.1002/jmv.70228","url":null,"abstract":"<p>The lack of effective antiviral treatments for enteroviruses, including human enterovirus A71 (EV-A71), have resulted in an immense global healthcare burden associated with hand-foot-and-mouth disease (HFMD). Rocaglates and aglains belong to a family of compounds produced by <i>Aglaia</i> genus plants. Since the initial discovery of rocaglates in 1982, various rocaglates and aglains have been synthesized and extensively studied mainly as anticancer agents. Here, we report the discovery of a novel aglain derivative as a potential EV-A71 inhibitor. From an immunofluorescence-based phenotypic screen of a library of 296 rocaglate and aglain derivatives, we identified a lead aglain which effectively suppressed EV-A71 replication by 2.3 log fold at a non-cytotoxic concentration, with a host cell CC₅₀ of 21.78 µM, an EV-A71 infection EC₅₀ of 3.57 µM, and a selectivity index of 6.1. Further validation revealed inhibition of EV-A71 across multiple human cell types and a pan-enterovirus inhibitory spectrum against other enteroviruses. Subsequent mechanistic investigation revealed interference with EV-A71 intracellular post-entry events including viral RNA transcription and translation. Findings from this study have established a strong foundation for development of aglain scaffolds as much needed antiviral agents for HFMD, paving the way for future medicinal chemistry optimization and <i>in vivo</i> studies.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immunogenicity of Coxsackievirus A6 (D3a Sub-Genotype) Virus-Like Particle and mRNA Vaccines","authors":"Huanhuan Lu,&nbsp;Jinbo Xiao,&nbsp;Jingdong Song,&nbsp;Yang Song,&nbsp;Hai Li,&nbsp;Hu Ren,&nbsp;Jichen Li,&nbsp;Ruyi Cong,&nbsp;Hangwen Li,&nbsp;Yi Fang,&nbsp;Dongmei Yan,&nbsp;Shuangli Zhu,&nbsp;Qiang Sun,&nbsp;Ying Liu,&nbsp;Yong Zhang","doi":"10.1002/jmv.70201","DOIUrl":"https://doi.org/10.1002/jmv.70201","url":null,"abstract":"<div>\u0000 \u0000 <p>In recent years, coxsackievirus A6 (CVA6) has surpassed enterovirus A71 to become the main pathogen causing severe Hand, Foot, and Mouth disease (HFMD) in China with a substantial disease burden. However, there is currently no commercial CVA6 vaccine. The D3a genotype of CVA6 is the predominant genotype in China. In this study, virus-like particles (VLPs) and mRNA vaccines based on the CVA6 sub-genotype D3a were successfully developed. The immunogenicity and protective effects of the VLP of CVA6 combined with Al(OH)₃ and CpG adjuvant indicated that VLP-induced neutralizing antibodies against three CVA6 sub-genotype (D2, D3a, and D3b) strains in Institute of Cancer Research (ICR) mice, and the combination of the two adjuvants enhanced cellular immunity. Passive immunization with serum from mice immunized with VLPs protected suckling mice against CVA6 lethal challenge in both antiserum transfer and maternal immunization experiments. The immunogenicity and protective effects of the mRNA vaccine of CVA6 indicate that it induces robust T-cell immunity. T-cell immunity was found to cross-protect against coxsackievirus A10 infection in mice. This is the first trial of a CVA6 mRNA vaccine worldwide and the first comparison of the immunogenicity and protective effects of VLP and mRNA vaccines based on D3a CVA6. The study provides a theoretical basis for the development of enteroviruses vaccines and the formulation of immunization strategies.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}