新生儿5微克重组乙型肝炎疫苗(酿酒酵母)无应答者不同剂次和剂量再免疫血清学效果研究

Study of Response to Revaccination of Hepatitis B Vaccine (HepB) with Different Schedule and Different Doses for Non-response Infants after Primary Immunization with 5μg HepB Made by Recombinant Deoxyribonucleic Acid Techniques in Saccharomyces Cerevisiae

目的评价新生儿接种5微克(μg)重组乙型肝炎(乙肝)疫苗(酿酒酵母)[Hepatitis B Vaccine(HepB)Made by Recombinant Deoxyribonucleic Acid Techniques in Saccharomyces Cerevisiae Yeast,HepB-SCY]后无应答者,使用不同剂次、剂量HepB再免疫后的血清学效果。方法抽取上海、山东、江苏、广西等省(自治区、直辖市)完成5μg HepBSCY全程免疫后的7~12月龄婴儿8945人,将其中的无应答者随机分为2组,分别采用5μg HepB-SCY和10μg HepB(汉逊酵母)(Hansenula Polymorpha Yeast,HPY),按0、1、6个月程序进行再免疫,于再免疫第1、3剂后各1个月采血检测抗乙肝病毒表面抗原抗体(Antibody to Hepatitis B Virus Surface Antigen Anti-HBs)。结果 5μg HepBSCY组再免疫第1、3剂后,Anti-HBs阳转率分别为78.95%(60/76)和91.67%(66/72),差异有统计学意义(χ2=4.73,P=0.03)。10μg HepB-HPY组再免疫第1、3剂后,Anti-HBs阳转率分别为92.65%(63/68)和100.00%(64/64),差异无统计学意义[费希尔(Fisher)精确检验法,P=0.06]。5μg HepB-SCY组再免疫第1、3剂后,Anti-HBs的几何平均浓度(Geometric Mean Concentration,GMC)分别为45.79毫国际单位/毫升(mIU/ml)和193.83mIU/ml,差异有统计学意义(t=3.55,P=0.001)。10μg HepB-HPY组再免疫第1、3剂后,GMC分别上升为107.71 mIU/ml和302.54mIU/ml,差异有统计学意义(t=3.52,P=0.001)。再免疫第1剂后,10μg HepB-HPY组Anti-HBs的GMC高于5μg HepB-SCY组,差异有统计学意义(t=-2.10,P=0.037)。结论对5μg HepB-SCY初次免疫后无应答婴儿使用5μg HepB-SCY再免疫3剂,或10μg HepB-HPY再免疫1剂,能获得较理想的免疫应答;再免疫3剂比1剂可获得更高的抗体水平。

Objective To evaluate the effect of booster immunization of hepatitis B vaccine （HepB） to the nonresponse infants after primary immunization of 5 μ g HepB made by recombinant deoxyribonucleic acid techniques in saccharomyces cerevisiae yeast（HepB-SCY）. Methods A total of 8945 infants of 7- 12 months old who were administered with 3 dosages of 5μg HepB-SCY according to 0-1-6 monthschedule were sampled in Shanghai, Shandong, Jiangshu and Guangxi, from which the non- response infants were randomly divided into 2 groups and given booster immunization according to 0-1-6 month schedule with 5 p^g HepB-SCY and 10p^g HepB hansenula polymorpha yeast （HPY）, respectively. Blood samples were collected 1 month later after 1st and 3rd dose booster respectively, and the titers of antibody to hepatitis B virus surface antigen （Anti-HBs） were detected. Results The Anti-HBs conversion rate of 5 p^g HepB- SCY group were 78.95% （60/76） and 91.67% （66/72） after the is＇ booster and the 3r~ booster, statistically significant difference （x2 = 4.73 ,P = 0. 03）. The Anti-HBs conversion rate of lOp^g HepB- HPY group was 92.65% （63/68） after the 1 s, booster and 100.00% （ 64/64 ） after the 3rd booster which has no statistically significant difference （ Fisher＇s exact test, P = 0.03 ）. Among 5 p^g HepB-SCY group, the geometric mean concentration （GMC） was 45.79 mIU/ml after 1st booster and 193.83mIU/ml after the 3r~ booster respectively, and the difference was statistically significant （t = 3.55, P = 0. 001 ）. For 10lxg HepB-HPY group, the GMC was 107.71mlU/ml after 15＇ booster and 302.54mlU/ml after the 3rd booster respectively, with statistically significant difference （t = 3.52, P = 0. 001 ）. The GMC of lOtxg HepB-HPY group was higher than that of 5 ixg HepB-SCY group after the 1 st booster with statistically significant difference （ t = - 2. 10, P = 0. 037 ）. Conclusions The re-vaccination of 3 doses of 5 Ixg HepB-SCY or 1 dose of 10txg HepB-HPY for infants of non-response to 3 doses of 51xg HepB-SCY primary immunization can achieve satisfactory immunological effect. Compared with 1 dose 10lxg HepB- HPY, with 3 doses 5lxg HepB-SCY can achieve higher GMC.