PMID- 37743201
OWN - NLM
STAT- MEDLINE
DCOM- 20231114
LR  - 20231124
IS  - 2095-9281 (Electronic)
IS  - 2095-9273 (Linking)
VI  - 68
IP  - 20
DP  - 2023 Oct 30
TI  - 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.
PG  - 2448-2455
LID - S2095-9273(23)00636-9 [pii]
LID - 10.1016/j.scib.2023.09.020 [doi]
AB  - The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine 
      (Cecolin) has received prequalification by the World Health Organization based on 
      its high efficacy and good safety profile. We aimed to evaluate the 
      immunogenicity and safety of the second-generation nonavalent HPV 
      6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded 
      phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly 
      (1:1) allocated to receive three doses of 1.0 mL (270 microg) of Cecolin 9 or placebo 
      with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and 
      geometric mean titer of neutralizing antibodies (nAbs) one month after the full 
      vaccination course (month 7). The secondary endpoint was the safety profile 
      including solicited adverse reactions occurring within 7 d, adverse events (AEs) 
      occurring within 30 d after each dose, and serious adverse events (SAEs) 
      occurring during the 7-month follow-up period. In total, 627 volunteers were 
      enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group 
      in Jiangsu Province, China. Almost all participants in the per-protocol set for 
      immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at 
      month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert 
      for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups 
      were 80.8% and 72.9%, respectively, with the majority of them being mild and 
      recovering shortly. None of the SAEs were considered related to vaccination. In 
      conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well 
      tolerated and immunogenic, which warrants further efficacy studies in larger 
      populations.
CI  - Copyright (c) 2023 Science China Press. Published by Elsevier B.V. All rights 
      reserved.
FAU - Hu, Yue-Mei
AU  - Hu YM
AD  - Jiangsu Provincial Center for Disease Control and Prevention, Public Health 
      Research Institute of Jiangsu Province, Nanjing 210009, China.
FAU - Bi, Zhao-Feng
AU  - Bi ZF
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Zheng, Ya
AU  - Zheng Y
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Zhang, Li
AU  - Zhang L
AD  - National Institutes for Food and Drug Control, Beijing 102629, China.
FAU - Zheng, Feng-Zhu
AU  - Zheng FZ
AD  - Xiamen Innovax Biotech Company, Xiamen 361027, China.
FAU - Chu, Kai
AU  - Chu K
AD  - Jiangsu Provincial Center for Disease Control and Prevention, Public Health 
      Research Institute of Jiangsu Province, Nanjing 210009, China.
FAU - Li, Ya-Fei
AU  - Li YF
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Chen, Qi
AU  - Chen Q
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Quan, Jia-Li
AU  - Quan JL
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Hu, Xiao-Wen
AU  - Hu XW
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Huang, Xing-Cheng
AU  - Huang XC
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Zhu, Kong-Xin
AU  - Zhu KX
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Wang-Jiang, Ya-Hui
AU  - Wang-Jiang YH
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Jiang, Han-Min
AU  - Jiang HM
AD  - Dongtai Center for Disease Control and Prevention, Yancheng 224200, China.
FAU - Zang, Xia
AU  - Zang X
AD  - Dongtai Center for Disease Control and Prevention, Yancheng 224200, China.
FAU - Liu, Dong-Lin
AU  - Liu DL
AD  - Dongtai Center for Disease Control and Prevention, Yancheng 224200, China.
FAU - Yang, Chang-Lin
AU  - Yang CL
AD  - Dongtai Center for Disease Control and Prevention, Yancheng 224200, China.
FAU - Pan, Hong-Xing
AU  - Pan HX
AD  - Jiangsu Provincial Center for Disease Control and Prevention, Public Health 
      Research Institute of Jiangsu Province, Nanjing 210009, China.
FAU - Zhang, Qiu-Fen
AU  - Zhang QF
AD  - Xiamen Innovax Biotech Company, Xiamen 361027, China.
FAU - Su, Ying-Ying
AU  - Su YY
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Huang, Shou-Jie
AU  - Huang SJ
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Sun, Guang
AU  - Sun G
AD  - Xiamen Innovax Biotech Company, Xiamen 361027, China. Electronic address: 
      guang_sun@innovax.cn.
FAU - Huang, Wei-Jin
AU  - Huang WJ
AD  - National Institutes for Food and Drug Control, Beijing 102629, China. Electronic 
      address: huangweijin@nifdc.org.cn.
FAU - Huang, Yue
AU  - Huang Y
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China. Electronic address: 
      huangyuesph@xmu.edu.cn.
FAU - Wu, Ting
AU  - Wu T
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China. Electronic address: 
      wuting@xmu.edu.cn.
FAU - Zhang, Jun
AU  - Zhang J
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
FAU - Xia, Ning-Shao
AU  - Xia NS
AD  - State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine 
      Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; 
      National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA 
      Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic 
      Technology, Xiamen University, Xiamen 361102, China.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20230919
PL  - Netherlands
TA  - Sci Bull (Beijing)
JT  - Science bulletin
JID - 101655530
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Papillomavirus Vaccines)
RN  - 0 (Vaccines, Combined)
RN  - 0 (Vaccines, Virus-Like Particle)
RN  - human papillomavirus 52
SB  - IM
MH  - Female
MH  - Humans
MH  - Antibodies, Neutralizing
MH  - Escherichia coli
MH  - Human Papillomavirus Viruses
MH  - Papillomaviridae
MH  - *Papillomavirus Infections/prevention & control
MH  - *Papillomavirus Vaccines/adverse effects
MH  - Vaccines, Combined
MH  - *Vaccines, Virus-Like Particle/adverse effects
MH  - Double-Blind Method
OTO - NOTNLM
OT  - 9-valent human papillomavirus vaccine
OT  - Escherichia coli
OT  - Human papillomavirus
OT  - Immunogenicity
OT  - Safety
COIS- Conflict of interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Feng-Zhu Zheng and Qiu-Fen Zhang report being either current employees 
      of Xiamen Innovax; Guang Sun report being current employees of and have stock 
      options in Xiamen Innovax. All other authors declare that they have no conflict 
      of interest.
EDAT- 2023/09/25 00:42
MHDA- 2023/11/06 06:41
CRDT- 2023/09/24 21:57
PHST- 2023/07/15 00:00 [received]
PHST- 2023/08/23 00:00 [revised]
PHST- 2023/09/14 00:00 [accepted]
PHST- 2023/11/06 06:41 [medline]
PHST- 2023/09/25 00:42 [pubmed]
PHST- 2023/09/24 21:57 [entrez]
AID - S2095-9273(23)00636-9 [pii]
AID - 10.1016/j.scib.2023.09.020 [doi]
PST - ppublish
SO  - Sci Bull (Beijing). 2023 Oct 30;68(20):2448-2455. doi: 
      10.1016/j.scib.2023.09.020. Epub 2023 Sep 19.