PMID- 37283969
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230608
IS  - 2666-6065 (Electronic)
IS  - 2666-6065 (Linking)
VI  - 34
DP  - 2023 May
TI  - 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.
PG  - 100731
LID - 10.1016/j.lanwpc.2023.100731 [doi]
LID - 100731
AB  - BACKGROUND: A safe and highly efficacious Escherichia coli (E. coli)-produced HPV 
      16/18 bivalent vaccine has been prequalified by the World Health Organization. 
      Here, we conducted a single-center, open-label, dose-escalation phase 1 clinical 
      trial to evaluate the safety and immunogenicity of the second-generation 
      nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine. METHOD: Twenty-four eligible 
      volunteers aged 18-45 years were enrolled in January 2019 in Dongtai, China and 
      received 0.5 mL (135 mug) or 1.0 mL (270 mug) of the candidate vaccine with a 
      0/1/6-month dose-escalation schedule. Local and systemic adverse events (AEs) 
      occurring within 30 days after each vaccination and serious adverse events (SAEs) 
      occurring within 7 months were recorded. Blood samples from each participant were 
      collected before and 2 days after the first and third vaccinations to determine 
      changes in laboratory parameters. Serum IgG and neutralizing antibody (nAb) 
      levels against each HPV type at month 7 were analyzed (ClinicalTrials.gov: 
      NCT03813940). FINDINGS: The incidences of total AEs in the 135 mug and 270 mug 
      groups were 66.7% and 83.3%, respectively. All AEs were mild or moderate, and no 
      SAEs were reported. No clinically significant changes were found in paired blood 
      indices before or after any of the vaccinations. All the participants in the 
      per-protocol set except for two who failed to seroconvert for HPV 11 or 58 in the 
      135 mug group seroconverted at month 7 for both IgG and nAbs. INTERPRETATION: The 
      candidate E. coli-produced 9vHPV vaccine has been preliminarily proven to be well 
      tolerated and immunogenic, which encourages further studies in large cohorts with 
      a wider age range. FUNDING: This study was supported by the National Natural 
      Science Foundation of China, Fujian Provincial Natural Science Foundation, Fujian 
      Province Health and Education Joint Research Program, Xiamen Science and 
      Technology Plan Project, Fundamental Research Funds for the Central Universities, 
      CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax 
      Biotechnology Co., Ltd.
CI  - (c) 2023 The Author(s).
FAU - Chu, Kai
AU  - Chu K
AD  - Jiangsu Provincial Center for Disease Control and Prevention, Public Health 
      Research Institute of Jiangsu Province, Nanjing, Jiangsu, China.
FAU - Bi, Zhao-Feng
AU  - Bi ZF
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Huang, Wei-Jin
AU  - Huang WJ
AD  - National Institutes for Food and Drug Control, Beijing, China.
FAU - Li, Ya-Fei
AU  - Li YF
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Zhang, Li
AU  - Zhang L
AD  - National Institutes for Food and Drug Control, Beijing, China.
FAU - Yang, Chang-Lin
AU  - Yang CL
AD  - Dongtai Center for Disease Control and Prevention, Yancheng, Jiangsu, China.
FAU - Jiang, Han-Min
AU  - Jiang HM
AD  - Dongtai Center for Disease Control and Prevention, Yancheng, Jiangsu, China.
FAU - Zang, Xia
AU  - Zang X
AD  - Dongtai Center for Disease Control and Prevention, Yancheng, Jiangsu, China.
FAU - Chen, Qi
AU  - Chen Q
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Liu, Dong-Lin
AU  - Liu DL
AD  - Dongtai Center for Disease Control and Prevention, Yancheng, Jiangsu, 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, Jiangsu, China.
FAU - Huang, Yue
AU  - Huang Y
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiang An Biomedicine Laboratory, Xiamen, Fujian, China.
FAU - Zheng, Feng-Zhu
AU  - Zheng FZ
AD  - Xiamen Innovax Biotech Company, Xiamen, Fujian, China.
FAU - Zhang, Qiu-Fen
AU  - Zhang QF
AD  - Xiamen Innovax Biotech Company, Xiamen, Fujian, China.
FAU - Sun, Guang
AU  - Sun G
AD  - Xiamen Innovax Biotech Company, Xiamen, Fujian, China.
FAU - Su, Ying-Ying
AU  - Su YY
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiang An Biomedicine Laboratory, Xiamen, Fujian, China.
FAU - Huang, Shou-Jie
AU  - Huang SJ
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiang An Biomedicine Laboratory, Xiamen, Fujian, China.
FAU - Pan, Hui-Rong
AU  - Pan HR
AD  - Xiamen Innovax Biotech Company, Xiamen, Fujian, China.
FAU - Wu, Ting
AU  - Wu T
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiang An Biomedicine Laboratory, Xiamen, Fujian, China.
FAU - Hu, Yue-Mei
AU  - Hu YM
AD  - Jiangsu Provincial Center for Disease Control and Prevention, Public Health 
      Research Institute of Jiangsu Province, Nanjing, Jiangsu, China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiang An Biomedicine Laboratory, Xiamen, Fujian, China.
FAU - Zhu, Feng-Cai
AU  - Zhu FC
AD  - Jiangsu Provincial Center for Disease Control and Prevention, Public Health 
      Research Institute of Jiangsu Province, Nanjing, Jiangsu, China.
FAU - Xia, Ning-Shao
AU  - Xia NS
AD  - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National 
      Institute of Diagnostics and Vaccine Development in Infectious Diseases, 
      Collaborative Innovation Center of Biologic Products, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiang An Biomedicine Laboratory, Xiamen, Fujian, China.
AD  - The Research Unit of Frontier Technology of Structural Vaccinology of Chinese 
      Academy of Medical Sciences, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT03813940
PT  - Journal Article
DEP - 20230313
PL  - England
TA  - Lancet Reg Health West Pac
JT  - The Lancet regional health. Western Pacific
JID - 101774968
PMC - PMC10240382
OTO - NOTNLM
OT  - 9-Valent
OT  - Escherichia coli
OT  - Human papillomavirus vaccine
OT  - Immunogenicity
OT  - Phase 1 clinical trial
OT  - Safety
COIS- F-Z Z (Feng-Zhu Zheng), and Q-FZ (Qiu-Fen Zhang) report being either current 
      employees of Xiamen Innovax; G S (Guang-Sun) and H-R P (Hui-Rong Pan) report 
      being current employees of and have stock options in Xiamen Innovax. No other 
      potential conflicts of interest relevant to this article were reported.
EDAT- 2023/06/07 13:10
MHDA- 2023/06/07 13:11
PMCR- 2023/03/13
CRDT- 2023/06/07 09:40
PHST- 2023/02/06 00:00 [received]
PHST- 2023/02/15 00:00 [accepted]
PHST- 2023/06/07 13:11 [medline]
PHST- 2023/06/07 13:10 [pubmed]
PHST- 2023/06/07 09:40 [entrez]
PHST- 2023/03/13 00:00 [pmc-release]
AID - S2666-6065(23)00049-4 [pii]
AID - 100731 [pii]
AID - 10.1016/j.lanwpc.2023.100731 [doi]
PST - epublish
SO  - Lancet Reg Health West Pac. 2023 Mar 13;34:100731. doi: 
      10.1016/j.lanwpc.2023.100731. eCollection 2023 May.