PMID- 36283897 OWN - NLM STAT- MEDLINE DCOM- 20221115 LR - 20230126 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 40 IP - 48 DP - 2022 Nov 15 TI - Immunogenicity and safety of two novel human papillomavirus 4- and 9-valent vaccines in Chinese women aged 20-45 years: A randomized, blinded, controlled with Gardasil (type 6/11/16/18), phase III non-inferiority clinical trial. PG - 6947-6955 LID - S0264-410X(22)01281-6 [pii] LID - 10.1016/j.vaccine.2022.10.022 [doi] AB - BACKGROUND: Human papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent). METHODS: 1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20-26, 27-35, or 36-45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference > -10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio > 0.5. RESULTS: Among the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded -10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios > 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths. CONCLUSIONS: This study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Shu, Yajun AU - Shu Y AD - Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou 510440, China. FAU - Yu, Yebin AU - Yu Y AD - Yangchun Center for Disease Control and Prevention, Guangdong 52960, China. FAU - Ji, Ying AU - Ji Y AD - Bovax Biotechnology Co., Ltd., Shanghai 201321, China. FAU - Zhang, Li AU - Zhang L AD - Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing 100081, China. FAU - Li, Yuan AU - Li Y AD - Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou 510440, China. FAU - Qin, Haiyang AU - Qin H AD - Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing 100081, China. FAU - Huang, Zhuhang AU - Huang Z AD - Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou 510440, China. FAU - Ou, Zhiqiang AU - Ou Z AD - Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou 510440, China. FAU - Huang, Meilian AU - Huang M AD - Yangchun Center for Disease Control and Prevention, Guangdong 52960, China. FAU - Shen, Qiong AU - Shen Q AD - Bovax Biotechnology Co., Ltd., Shanghai 201321, China. FAU - Li, Zehong AU - Li Z AD - Bovax Biotechnology Co., Ltd., Shanghai 201321, China. FAU - Hu, Meng AU - Hu M AD - Bovax Biotechnology Co., Ltd., Shanghai 201321, China. FAU - Li, Chunyun AU - Li C AD - Bovax Biotechnology Co., Ltd., Shanghai 201321, China. FAU - Zhang, Gaoxia AU - Zhang G AD - Chongqing Bovax Biopharmaceutical Co., Ltd., Chongqing 401338, China. Electronic address: zhanggaoxia@bovax.com.cn. FAU - Zhang, Jikai AU - Zhang J AD - Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou 510440, China. Electronic address: gdswyw_sps@cdcp.org.cn. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20221022 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18) RN - 0 (Antibodies, Viral) RN - 0 (Papillomavirus Vaccines) SB - IM MH - Female MH - Humans MH - Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/adverse effects MH - *Papillomavirus Infections/prevention & control MH - Gammapapillomavirus MH - Antibodies, Viral MH - *Papillomavirus Vaccines MH - *Uterine Cervical Neoplasms/prevention & control MH - Papillomaviridae MH - China MH - Immunogenicity, Vaccine OTO - NOTNLM OT - Human papillomavirus OT - Immunogenicity OT - Non-inferiority trial OT - Recombination vaccine OT - Safety COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/10/26 06:00 MHDA- 2022/11/16 06:00 CRDT- 2022/10/25 22:04 PHST- 2022/08/14 00:00 [received] PHST- 2022/09/27 00:00 [revised] PHST- 2022/10/07 00:00 [accepted] PHST- 2022/10/26 06:00 [pubmed] PHST- 2022/11/16 06:00 [medline] PHST- 2022/10/25 22:04 [entrez] AID - S0264-410X(22)01281-6 [pii] AID - 10.1016/j.vaccine.2022.10.022 [doi] PST - ppublish SO - Vaccine. 2022 Nov 15;40(48):6947-6955. doi: 10.1016/j.vaccine.2022.10.022. Epub 2022 Oct 22.