Hong-Xing Pan1, Ying Zeng2, Xue-Fang Song2, Yi-Ju Zhang1, Ke Xu1, Zheng-Lun Liang3, Feng-Cai Zhu4. 1. Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, PR China. 2. Shenzhen Kangtai Biological Products Co., Ltd., Shenzhen 518057, Guangdong, PR China. 3. National Institute for Food and Drug Control, Beijing 100050, PR China. Electronic address: lzlun@yahoo.com. 4. Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, PR China. Electronic address: jszfc@vip.sina.com.
Abstract
CONTEXT: 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. DESIGN SETTING, AND PARTICIPANTS: 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. CONCLUSION: 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.
CONTEXT: 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. DESIGN SETTING, AND PARTICIPANTS: 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. CONCLUSION: 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.