{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:54:58Z","timestamp":1792806898838,"version":"4.5.0"},"reference-count":21,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Natural Science Foundation of China (NSFC) and the Bill &amp; Melinda Gates Foundation joint program","award":["7231101367"],"award-info":[{"award-number":["7231101367"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the National Natural Science Foundation of China (NSFC) and the Bill &amp; Melinda Gates Foundation joint program","award":["2023YFVA1002"],"award-info":[{"award-number":["2023YFVA1002"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Prophylactic human papillomavirus (HPV) vaccination substantially alleviates cervical cancer burden. This study aimed to evaluate the safety, tolerability, and immunogenicity of an Escherichia coli-expressed recombinant nonavalent HPV vaccine. Methods: A dose-escalating phase 1 clinical trial was conducted in Sheyang County, Jiangsu Province, China. Each participant received either the test vaccine or the control vaccine (Gardasil 9) following a 0\/2\/6-month schedule. Adverse reactions (ARs) within 7 days after vaccination, adverse events (AEs) within 30 days, and serious adverse events (SAEs) throughout the study were recorded. Blood parameters were measured before and 3 days after each dose. Serum immunoglobulin G (IgG) and neutralizing antibodies (nAbs) against nine HPV types were analyzed at months 0, 3, and 7. Results: A total of 160 women aged 18\u201345 years were enrolled, and 155 participants completed the full vaccination regimen. Within 7 days following vaccination, the incidence of ARs ranged from 56.67% to 90.00%, with the low-dose group showing a significantly higher rate than the control group (p = 0.004). Most AEs were mild or moderate, and no vaccine-related SAEs occurred. No significant differences were observed among the four groups regarding the incidence of abnormal laboratory findings. Seroconversion rates for nAbs and IgG against nine HPV types exceeded 97.92% following three doses. High levels of nAbs and IgG were observed at months 3 and 7, with geometric mean titers (GMTs) showing further increases by month 7. Conclusions: This new recombinant nonavalent HPV vaccine exhibits good tolerability and strong immunogenicity among women aged 18\u201345 years, supporting further efficacy studies in larger populations.<\/jats:p>","DOI":"10.3390\/vaccines13050511","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T03:59:26Z","timestamp":1747108766000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Safety, Tolerability, and Immunogenicity of a Recombinant Nonavalent Human Papillomavirus Vaccine (Escherichia coli) in Healthy Chinese Women Aged 18\u201345 Years: A Phase 1 Clinical Trial"],"prefix":"10.3390","volume":"13","author":[{"given":"Mingwei","family":"Wei","sequence":"first","affiliation":[{"name":"School of Public Health, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing 210009, China"},{"name":"Jiangsu Provincial Medical Innovation Center, National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Han","sequence":"additional","affiliation":[{"name":"School of Public Health, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sheyang City Center for Disease Control and Prevention, Yancheng 224499, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Health Guard Biotechnology Inc., Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Beijing Health Guard Biotechnology Inc., Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7033-5151","authenticated-orcid":false,"given":"Jingxin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing 210009, China"},{"name":"Jiangsu Provincial Medical Innovation Center, National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3111-4325","authenticated-orcid":false,"given":"Wenjuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Vaccine Clinical Evaluation, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing 210009, China"},{"name":"Jiangsu Provincial Medical Innovation Center, National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wu, S., Jiao, J., Yue, X., and Wang, Y. (2024). Cervical cancer incidence, mortality, and burden in China: A time-trend analysis and comparison with England and India based on the global burden of disease study 2019. Front. Public. Health, 12.","DOI":"10.3389\/fpubh.2024.1358433"},{"key":"ref_2","unstructured":"World Health Organization (2025, February 25). Cancer Today-World. Available online: https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/populations\/900-world-fact-sheet.pdf."},{"key":"ref_3","unstructured":"World Health Organization (2025, February 25). Cancer Today-China. Available online: https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/populations\/160-china-fact-sheet.pdf."},{"key":"ref_4","unstructured":"National Cancer Institute (2025, February 25). 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Bull."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/S1473-3099(22)00435-2","article-title":"Efficacy, safety, and immunogenicity of an Escherichia coli-produced Human Papillomavirus (16 and 18) L1 virus-like-particle vaccine: End-of-study analysis of a phase 3, double-blind, randomised, controlled trial","volume":"22","author":"Zhao","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/jnci\/djz074","article-title":"Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial","volume":"112","author":"Qiao","year":"2020","journal-title":"J. Natl. 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Pac."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e20154387","DOI":"10.1542\/peds.2015-4387","article-title":"Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials","volume":"138","author":"Block","year":"2016","journal-title":"Pediatrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1016\/j.vaccine.2023.04.009","article-title":"Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9-45 years: A randomized, double-blind, placebo-controlled phase 1 clinical trial","volume":"41","author":"Li","year":"2023","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"734","DOI":"10.4161\/hv.27316","article-title":"Characterization of virus-like particles in GARDASIL\u00ae by cryo transmission electron microscopy","volume":"10","author":"Zhao","year":"2014","journal-title":"Hum. 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A review of the literature","volume":"8","author":"Pattyn","year":"2019","journal-title":"Papillomavirus Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5118","DOI":"10.1016\/j.vaccine.2014.05.030","article-title":"Safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: A Phase I dose escalating study in healthy volunteers","volume":"32","author":"Heldens","year":"2014","journal-title":"Vaccine"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/5\/511\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:31:37Z","timestamp":1760031097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/5\/511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":21,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["vaccines13050511"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13050511","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]}}}