Stevens Cladd E, Toy Pearl, Kamili Saleem, Taylor Patricia E, Tong Myron J, Xia Guo-Liang, Vyas Girish N
New York Blood Center, 310 East 67th Street, New York, NY, 10021, United States.
University of California School of Medicine, San Francisco, CA, 94143-0134, United States.
Biologicals. 2017 Nov;50:3-19. doi: 10.1016/j.biologicals.2017.08.008. Epub 2017 Sep 2.
Prevention of hepatitis B virus (HBV) transmission from infected mothers to their newborns is critical to HBV control and eventual eradication. Mother-to-child perinatal transmission causes the highest chronic carrier rate (>85%) with a high rate of subsequent chronic liver disease and hepatocellular carcinoma. This risk is reduced by 90% with HBV vaccine given along with hepatitis B immune globulin (HBIG) starting at birth. New analyses of our data from US trials of HBIG and HBV vaccine in high-risk infants revealed better efficacy with yeast-recombinant vaccine than plasma-derived vaccine, especially in preventing late onset infections, with evidence that vaccine prevented transmission of maternal HBV infection with the glycine to arginine mutation in surface antigen codon 145 (sG145R). Most late infections with sG145R were in vaccine non-responders, suggesting escape from HBIG rather than from vaccine-induced antibody. Our findings also help explain survey results from Taiwan following universal childhood immunization implemented in the mid-1980s. We conclude that current vaccines will remain effective against surface antigen mutants. Anti-viral drugs in high-risk pregnant women, in combination with newborn HBIG and vaccine, show promise for eliminating residual breakthrough neonatal infections, critical to meeting WHO 2030 goals and for eradicating HBV.
预防乙型肝炎病毒(HBV)从感染母亲传播给新生儿对于控制HBV并最终根除该病毒至关重要。母婴围产期传播导致最高的慢性携带者率(>85%),随后发生慢性肝病和肝细胞癌的几率也很高。从出生开始同时给予乙肝疫苗和乙肝免疫球蛋白(HBIG)可将这种风险降低90%。我们对美国针对高危婴儿进行的HBIG和乙肝疫苗试验数据的新分析显示,酵母重组疫苗比血浆源性疫苗疗效更好,尤其是在预防迟发性感染方面,有证据表明该疫苗可预防表面抗原密码子145(sG145R)发生甘氨酸到精氨酸突变的母体HBV感染的传播。大多数携带sG145R的迟发性感染发生在疫苗无应答者中,这表明是逃避了HBIG而非疫苗诱导的抗体。我们的研究结果也有助于解释台湾在20世纪80年代中期实施儿童普遍免疫接种后的调查结果。我们得出结论,当前的疫苗对表面抗原突变体仍将有效。高危孕妇使用抗病毒药物,再结合新生儿HBIG和疫苗,有望消除残留的突破性新生儿感染,这对于实现世界卫生组织2030年目标以及根除HBV至关重要。