Abstract：Objective To evaluate the safety of 60 μg recombinant hepatitis B vaccine（Saccharomyces Cerecisiae）in healthy population over 16 years old and immunogenicity in non-responders. Methods A total of 4 345 eligible subjects over 16 years old were selected and vaccinated with 60 μg recombinant hepatitis B vaccine, including 3 415 participants who have never been vaccined before and 930 non-responders. All participants were monitored for any adverse events occurring within 30 min after each injection and instructed to record selected injection-site reactions and systemic reactions on the day of vaccination and the subsequent 28 days. Blood samples were collected from non-responders at pre-vaccination and one month after vaccination,in order to determine anti-HBs levels,positive rates of anti-HBs and the mean geometric titre（GMT）of anti-HBs. Results Among 4 345 vaccinated participants,16.39 % of them reported at least one injection-site or systemic adverse reaction. The most common injection-site and systemic adverse reactions were Grade 1 adverse reactions with the incidence of 15.12 %（657/4 345）and 4.05%（176/4 345）respectively. No serious adverse events were observed. Among 930 non-responders,the positive rate of anti-HBs was 87.03 % with active responder of 76.74 %（551 / 718）and the GMT of anti-HBs was 479.28 mIU / ml. The positive rate of anti-HBs was not associated with gender or age（P>0.05）. The GMT of anti-HBs demonstrated significant differences between female and male （560.66 mIU / mL VS. 404.91 mIU / mL,P<0.05）,but there was no significant differences in different age groups（P>0.05）. Conclusion 60 μg recombinant hepatitis B vaccine was safe for healthy adults above 16 years and had good immunity efficacy among non-responders who had no or low response to standard immunization regimen of hepatitis B vaccine.
WANG Z Z,LI M Q,WANG P,et al. Comparative immunogenicity of hepatitis B vaccine with different dosages and schedules in healthy young adults in China[J]. Vaccine ,2016 ,34 （8）：1034-1039.
SHOUVAL D,ROGGENDORF H,ROGGENDORF M. Enhanced immune response to hepatitis B vaccination through immunization with a Pre-S1/Pre-S2/S vaccine[J]. Medical Microbiology and Immunology ,2015 ,204（1）：57-68.
DUAN Z J,CHEN X,LIANG Z,et al. Genetic polymorphisms of CXCR5 and CXCL13 are associated with non-responsiveness to the hepatitis B vaccine[J]. Vaccine ,2014,32（41）：5316-5322.
LI Z K,NIE J J,LI J,et al. The effect of HLA on immunological response to hepatitis B vaccine in healthy people：A meta-analysis[J]. Vaccine,2013 ,31 （40）：4355-4361.
FILIPPELLI M ,LIONETTI E ,GENNARO A ,et al. Hepatitis B vaccine by intradermal route in non responder patients：an update[J]. World Journal of Gastroenterology,2014,20 （30）：10383-10394.
SAYAD B ,VAZIRIAN A ,VAZIRI S ,et al. Effects of oral levamisole as an adjuvant to hepatitis B vaccine in health-care workers non-responders to previous vaccinations：A randomised controlled trial[J]. Journal of Clinical Virology ,2015 （69）：241-242.
PAN H X ,ZENG Y ,SONG X F ,et al. Immune response to hepatitis B vaccine with high antigen content in non-responders after standard primary vaccination in Chinese adults[J]. Vaccine ,2014 ,32 （29）：3706-3712.