title: Immune response to hepatitis B vaccine with high antigen content in non-responders after standard primary vaccination in Chinese adults.
abstract: BACKGROUND
  Alternative schedules are needed to provide greater immunogenicity in adults who fail to respond to the standard hepatitis B (HB) vaccine regimen.
  
  
  OBJECTIVE
  To evaluate the immunogenicity and safety of high antigen content HB vaccine formulations administered to non-responders after routine primary vaccination.
  
  
  METHODS
  This was a phase III, double-blind, controlled clinical trial in China. We enrolled healthy participants (16-60 years old) seronegative for HB surface (HBs) antigen after primary vaccination, who had HBs antibody (anti-HBs) titres <10 mIU/ml at 28 days following routine vaccination with licensed HB vaccine containing 10 μg of antigen. Participants were randomised (2:2:1) to receive three booster doses of HB vaccine formulations containing 60 μg, 30 μg or 10 μg of antigen per dose 28 days apart. Blood samples were obtained pre-vaccination and 28 days after each dose to assess immunogenicity. Reactogenicity and safety were evaluated up to 28 days after each vaccine dose.
  
  
  RESULTS
  Seroconversion rates were ≥ 92.1% and ≥ 87.1% as from the second dose of the 60 μg and 30 μg HB vaccine formulations, respectively, with geometric mean concentrations (GMCs) of ≥ 286.0 mIU/ml and ≥ 164.0 mIU/ml. In the 10 μg HB vaccine group the seroconversion rates were ≥ 83.0% and the GMCs ≥ 110.1 mIU/ml as from the second vaccine dose. All HB vaccine formulations were well tolerated: 352/1091 (32.3%) participants reported at least one injection-site or systemic adverse reaction (145/434 [33.4%] from the 60μg group; 138/435 [31.7%] from the 30 μg group and 69/222 [31.1%] from the 10 μg group). Most reactions were mild or moderate and resolved within 24h. No serious adverse events were reported.
  
  
  CONCLUSIONS
  Booster vaccination with a three-dose schedule of a high antigen content HB vaccine formulation was immunogenic and well tolerated in healthy adults. Clinicaltrialsgov Identifier: NCT01203319.
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, PR China.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Pan
authors.affiliation: Shenzhen Kangtai Biological Products Co., Ltd., Shenzhen 518057, Guangdong, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Shenzhen Kangtai Biological Products Co., Ltd., Shenzhen 518057, Guangdong, PR China.
authors.forename: Xue-Fang
authors.initials: XF
authors.lastname: Song
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, PR China.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: National Institute for Food and Drug Control, Beijing 100050, PR China. Electronic address: lzlun@yahoo.com.
authors.forename: Zheng-Lun
authors.initials: ZL
authors.lastname: Liang
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, PR China. Electronic address: jszfc@vip.sina.com.
authors.forename: Feng-Cai
authors.initials: FC
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D004311:Double-Blind Method; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic
keywords: Hepatitis B vaccine with high antigen content; Hepatitis B virus; Immunogenicity; Non-responder