{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:32:04Z","timestamp":1763127124509,"version":"3.45.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Vaccination with prophylactic human papillomavirus (HPV) vaccines is one of the most effective measures to prevent cervical cancer and other related diseases. Here we aimed to evaluate the immunogenicity and safety of an\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      -produced 9-valent human papillomavirus (9vHPV) vaccine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We did a single-center, randomized, observer-blinded, positive controlled phase 2 clinical trial in healthy women aged 20\u201345 years. All eligible participants were randomly assigned (1:1:1) to receive 270 ug 9vHPV, 360 ug 9vHPV, or the control vaccine (Gardasil) with a 0\u20132\u20136-month schedule. Serum samples were collected at day 0 and month 7 to assess IgG and neutralizing antibodies (nAbs). For HPV 6\/HPV 11\/HPV 16\/HPV 18, non-inferiority was identified for the lower limit of the 95% CI of the geometric mean titer (GMT) ratio at a margin of 0.5 and a seroconversion rate (SCR) difference at a margin of -5%. For HPV 31\/HPV 33\/HPV 45\/HPV 52\/HPV 58, superiority was demonstrated if the lower limit of the 95% CI for GMT ratio is greater than 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 780 participants aged 20\u201345 years were enrolled, among whom 770 completed the three-dose immunization schedule. The incidences of ARs within 7 days in the 270 \u03bcg, 360 \u03bcg, and positive control groups were 38.85%, 41.92%, and 22.69%, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). The GMTs of nAbs and IgG antibodies for nine HPV types in both 270 ug and 360 ug groups showed an obvious rise at month 7. For HPV 31\/HPV 33\/HPV 45\/HPV 52\/HPV 58, the GMTs of nAbs in both 270 \u03bcg and 360 \u03bcg groups were higher than those in the positive control group, with the 95% CI lower bounds of GMT ratios all greater than 1. Compared to the positive control group, HPV 6 and HPV 18 achieved non-inferiority criteria for GMT in both dose groups. However, the GMT ratio of HPV 16 in the 270 \u03bcg group was 0.46 (0.38\u20130.55), and HPV 16 and HPV 11 in the 360 \u03bcg group were 0.48 (0.40\u20130.58) and 0.53 (0.46\u20130.60), respectively. The SCRs of nAbs for HPV 6\/HPV 11\/HPV 16\/HPV 18 in the three groups were 100%, with the 95% CI lower bound for SCR differences ranging from -2.55% to -1.64%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The candidate 9vHPV vaccine was well tolerated and immunogenic, supporting further evaluation for efficacy and safety in larger populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov<\/jats:ext-link>\n                      , identifier NCT05694728.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1706662","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:27:02Z","timestamp":1763126822000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunogenicity and safety of an Escherichia coli-produced 9-valent human papillomavirus vaccine (types 6\/11\/16\/18\/31\/33\/45\/52\/58) in healthy Chinese women aged 20\u201345 years: a single-center, randomized, observer-blinded, positive controlled phase 2 clinical 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Drug approval certificate delivery information\n          \n          \n          2025"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00275-X","article-title":"Head-to-head immunogenicity comparison of an Escherichia coli-produced 9-valent human papillomavirus vaccine and Gardasil 9 in women aged 18\u201326 years in China: a randomised blinded clinical trial","volume":"23","author":"Zhu","year":"2023","journal-title":"Lancet Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2092363","DOI":"10.1080\/21645515.2022.2092363","article-title":"Safety and immunogenicity of an Escherichia coli-produced bivalent human papillomavirus type 6\/11 vaccine: A dose-escalation, randomized, double-blind, placebo-controlled phase 1 trial","volume":"18","author":"Mo","year":"2022","journal-title":"Hum Vaccin Immunother"},{"key":"B16","doi-asserted-by":"publisher","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":"Moreira","year":"2016","journal-title":"Pediatrics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"100731","DOI":"10.1016\/j.lanwpc.2023.100731","article-title":"Safety and immunogenicity of an Escherichia coli-produced 9-valent human papillomavirus L1 virus-like particle vaccine (types 6\/11\/16\/18\/31\/33\/45\/52\/58) in healthy adults: an open-label, dose-escalation phase 1 clinical trial","volume":"34","author":"Chu","year":"2023","journal-title":"Lancet Reg Health West Pac"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2023.09.020","article-title":"Immunogenicity and safety of an Escherichia coli-produced human papillomavirus (types 6\/11\/16\/18\/31\/33\/45\/52\/58) L1 virus-like-particle vaccine: a phase 2 double-blind, randomized, controlled trial","volume":"68","author":"Hu","year":"2023","journal-title":"Sci Bull (Beijing)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.05.110","article-title":"Chapter 12: Prophylactic HPV vaccines: underlying mechanisms","author":"Stanley","year":"2006","journal-title":"Vaccine"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31821-4","article-title":"Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16\u201326 years: a randomised, double-blind trial","volume":"390","author":"Huh","year":"2017","journal-title":"Lancet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines13050511","article-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","volume":"13","author":"Wei","year":"2025","journal-title":"Vaccines (Basel)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.02.057","article-title":"Trivalent Human Papillomavirus (HPV) VLP vaccine covering HPV type 58 can elicit high level of humoral immunity but also induce immune interference among component types","volume":"28","author":"Zhang","year":"2010","journal-title":"Vaccine"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71179-9","article-title":"Next generation prophylactic human papillomavirus vaccines","volume":"16","author":"Schiller","year":"2015","journal-title":"Lancet Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djaa011","article-title":"Evaluation of durability of a single dose of the bivalent HPV vaccine: the CVT trial","volume":"112","author":"Kreimer","year":"2020","journal-title":"J Natl Cancer Inst"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1706662\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:27:03Z","timestamp":1763126823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1706662\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,14]]},"references-count":24,"alternative-id":["10.3389\/fimmu.2025.1706662"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1706662","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,14]]},"article-number":"1706662"}}