Improved prevention of perinatal hepatitis B transmission HBV by employing the Bio-Hep-B PreS1/PreS2/S HBV vaccine in new born babies from HBV positive mothers

尽管接种了疫苗，但母婴传播率升高的巴勒斯坦人口中的乙肝病毒感染率很高，我们将进行以下工作：1.通过筛查抗-HBc抗体、乙肝表面抗原和抗-HBs，确定巴勒斯坦孕妇中乙肝病毒感染的流行率。2.了解HBs Ag阳性母亲的乙肝病毒感染状况(HBeAg和HBVDNA载量)。3.在乙肝表面抗原阳性母亲的新生儿中，我们将比较只含S-乙肝表面抗原蛋白的传统英格力斯B疫苗和含PreS1、PreS2、S的替代许可疫苗(包括全部三种乙肝表面抗原蛋白的Bio-Hep-B)的效果。4.通过对接种疫苗的儿童进行至少一年的跟踪调查，确定在这种特定环境下接种疫苗的失败率。他们将接受HBs Ag、HBVDNA、抗-HBc、抗-HBs检测，如果抗-HBc阳性，则进一步检测乙肝病毒标志物。5.调查疫苗接种失败的主要原因：是否与野生型乙肝病毒突破或逃逸突变有关？为此，我们将利用分子生物学工具对所有HBVDNA阳性母亲和婴儿的preS/S基因区域进行扩增和测序。基因分型数据将被分析，并与已知的基因类型进行比较。疫苗诱导的针对乙肝病毒逃逸突变的抗体的中和潜力应在体外进行研究。6.根据这项研究数据提出的最后建议应作为巴勒斯坦卫生机构考虑优化疫苗接种方案和使用的疫苗类型的参考。

As HBV prevalence is high in the Palestinian population with elevated mother to child transmission in spite of vaccination, we will perform the following: 1. Determine the prevalence of HBV infection in pregnant Palestinian women, by screening for anti-HBc antibodies, HBsAg and anti-HBs. 2. Characterise the state of HBV infection in HBsAg positive mothers (HBeAg and HBV DNA load). 3. In the newborn babies of HBsAg positive mothers, we will compare the efficacy of the conventional Engerix B vaccine that contains only the S-HBsAg protein with an alternative licensed PreS1, PreS2, S-containing vaccine (Bio-Hep-B that includes all three HBsAg proteins). 4. Determine the failure rate of vaccination in this particular setting by following the vaccinated children for at least one year. They will be tested for HBsAg, HBV DNA, anti-HBc, anti-HBs and if positive for anti-HBc for further HBV markers. 5. Investigate the major reason for vaccination failures: is it related to a breakthrough of wild type HBV or escape mutants? For this purpose we will employ molecular biology tools to amplify and sequence the preS/S gene region of all HBV DNA positive mothers and infants. The genotyping data will be analysed and compared to known genotypes. The neutralising potential of vaccine-induced antibodies against HBV escape mutants shall be studied in vitro. 6. A final recommendation based on this research data should be a reference for the Palestinian health institution to consider the optimisation of the vaccination program and the type of vaccine to be used.