Identification of host genetic factors associated with response to a HB vaccination

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08986
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: SAWAI Hiromi 東京大学, 大学院医学系研究科(医学部), 助教 (60377124)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: B型肝炎 / 疾患関連遺伝子

Outline of Final Research Achievements

The GWAS and HLA association tests were carried out using a total of 1,193 Japanese individuals including low responders, intermediate responders, and high responders. Classical HLA class II alleles were statistically imputed using the genome-wide SNP typing data. The GWAS identified independent associations of HLA-DRB1-DQB1, HLA-DPB1 and BTNL2 genes. Five HLA DRB1-DQB1 haplotypes and two DPB1 alleles showed significant associations with response to the HB vaccine in a comparison of three groups of 1,193 HB vaccinated individuals. When frequencies of DRB1-DQB1 haplotypes and DPB1 alleles were compared between low immune responders and HBV patients, significant associations were identified for three DRB1-DQB1 haplotypes, and no association was identified for any of the DPB1 alleles. In contrast, no association was identified for DRB1-DQB1 haplotypes and DPB1 alleles in a comparison between high immune responders and healthy individuals.

Free Research Field

ゲノム医科学

Academic Significance and Societal Importance of the Research Achievements

世界180カ国以上でHBワクチン接種は行われており、日本ではGenotype Cに対応するHBワクチン（ビームゲン）が使用されてきた。しかし、ビームゲン接種者のうち約10％はHBs抗体を獲得できず、その原因は不明であった。本研究により、特定のHLA-DR-DQ分子によるHBs抗原の認識（ワクチン低反応）、およびBTNL2分子によるT細胞やB細胞の活性制御（ワクチン高反応）がHBワクチンの効果に重要な役割を果たすことが明らかとなり、今後国際共同等を進めることで、ユニバーサルワクチネーションが行われている日本やその他の国において、HBワクチンの適正かつ効率的な使用方法の確立が期待できる。