title: Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial.
abstract: BACKGROUND
  This study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.
  
  
  METHODS
  This randomized, double-blinded, controlled phase 2 trial enrolled women aged 18-25 years in China. Totally 1600 eligible participants were randomized to receive 90μg, 60μg, or 30μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.
  
  
  RESULTS
  All but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60μg (GMT=10,548) and 90μg (GMT=12,505) HPV vaccine groups and were significantly higher than those in the 30μg (GMT=7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.
  
  
  CONCLUSIONS
  The prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18-25 years. The 60μg dosage formulation was selected for further investigation for efficacy.
  
  
  BACKGROUND
  NCT01356823.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biological Products, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China. Electronic address: huyuemei@hotmail.com.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Hu
authors.affiliation: National Institute for Food and Drug Control, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biological Products, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Shou-Jie
authors.initials: SJ
authors.lastname: Huang
authors.affiliation: National Institute for Food and Drug Control, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Dongtai Center for Disease Control and Prevention, Dongtai, Jiangsu Province, China.
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: Dongtai Center for Disease Control and Prevention, Dongtai, Jiangsu Province, China.
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Yang
authors.affiliation: Dongtai Center for Disease Control and Prevention, Dongtai, Jiangsu Province, China.
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Jiang
authors.affiliation: Dongtai Center for Disease Control and Prevention, Dongtai, Jiangsu Province, China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Xiamen Innovax Biotech Company, Ltd, Xiamen, China.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Lin
authors.affiliation: Xiamen Innovax Biotech Company, Ltd, Xiamen, China.
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biological Products, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biological Products, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Fei-Xue
authors.initials: FX
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biological Products, School of Public Health, Xiamen University, Xiamen, China; School of Life Science, Xiamen University, Xiamen, China.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Li
authors.affiliation: National Center for Biotechnology Development, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors.forename: Feng-Cai
authors.initials: FC
authors.lastname: Zhu
authors.affiliation: National Institute for Food and Drug Control, Beijing, China.
authors.forename: Chang-Gui
authors.initials: CG
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biological Products, School of Public Health, Xiamen University, Xiamen, China. Electronic address: zhangj@xmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biological Products, School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Ning-Shao
authors.initials: NS
authors.lastname: Xia
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002681:China; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D053918:Papillomavirus Vaccines; D014614:Vaccines, Synthetic
keywords: Human papillomavirus; Immunogenicity; Randomized controlled clinical trial; Safety; Vaccine