Human Leukocyte Antigen Polymorphisms Associated with the Efficacy of Hepatitis B Virus Vaccination

Background: Genome Wide Association Studies (GWAS) and Human Leukocyte antigen (HLA) DRB1 and DPB1 typing have recently been applied to explore a host of genetic determinants of long-term immunological memory against HBV (hepatitis B virus) vaccination. However, the application of next generation sequencing (NGS) and the further exploration of HLA class II (HLA-DPA1, DQA1/B1, DRA1) typing in assessing the long-term immunological memory against HB vaccination have not yet been well established. In addition, there is a lack of data to explain the associations between HLA typing and single-nucleotide polymorphisms (SNP) along with the long-term immunological protectivity, null protectivity and residual protectivity of HBV vaccination. Hence, the purpose of this research project is to evaluate the host genetic determinants of long-term immunological memory against HB vaccination using the application of HLA typing and NGS. Material and methods: Participants will be recruited from the Family Medicine Clinics of Taipei Medical University who ask for HBsAg (hepatitis B virus surface antigen), HBcAb (hepatitis B virus core antibody) and HBsAb (hepatitis B virus surface antibody) tests. The inclusion criteria for these participants include that they are aged between 20 and 30 years, have completed the neonatal HBV vaccination scheme, and have not received an HBV vaccine booster since childhood. Subjects will be grouped according to their serous HBsAg and HBsAb titers. The control group will consist of those subjects with HBsAb>100mIU at the time of their heath examination. The case group will consist of subjects who present with HBsAb<10mIU and received an HBV vaccine booster. The case group will be sub-divided into: (a) subjects with HBsAb>100mIU after receiving one dose of HBV vaccine booster, (b) subjects with HBsAb≥10mIU after receiving three doses of HBV vaccine booster, and (c) subjects with HBsAb<10mIU after receiving three doses of HBV vaccine booster. HLA typing will be carried out with the use of the LIFECODES PCR reverse SSO (Sequence Specific Oligonucleotide) system. The NGS technique will be used with Illumina Genome Analyzer II. Expecting results: We expect to echo the association between HLA-DRB1 polymorphisms and the efficacy of HBV vaccine boosters as reported by previous studies. We will also identify the association between the immunological status of individuals who received HBV vaccine boosters and HLA-DPA1/B1 and even HLA-A, -B, -C. We will identify particular SNPs on HLA with the efficacy of the HBV vaccine booster by applying NGS analysis. As a consequence, our results will help to better inform regulatory bodies debating the administration of HBV vaccine boosters.