학술논문
Importance of HBsAg recognition by HLA molecules as revealed by responsiveness to different hepatitis B vaccines.
Document Type
Article
Author
Nishida, Nao; Sugiyama, Masaya; Ohashi, Jun; Kawai, Yosuke; Khor, Seik-Soon; Nishina, Sohji; Yamasaki, Kazumi; Yazaki, Hirohisa; Okudera, Kaori; Tamori, Akihiro; Eguchi, Yuichiro; Sakai, Aiko; Kakisaka, Keisuke; Sawai, Hiromi; Tsuchiura, Takayo; Ishikawa, Miyuki; Hino, Keisuke; Sumazaki, Ryo; Takikawa, Yasuhiro; Kanda, Tatsuo
Source
Subject
*HEPATITIS B vaccines
*GENOTYPES
*GENOMES
*HAPLOTYPES
*FUNCTIONAL analysis
*
*
*
*
Language
ISSN
2045-2322
Abstract
Hepatitis B (HB) vaccines (Heptavax-II and Bimmugen) designed based on HBV genotypes A and C are mainly used for vaccination against HB in Japan. To determine whether there are differences in the genetic background associated with vaccine responsiveness, genome-wide association studies were performed on 555 Heptavax-II and 1193 Bimmugen recipients. Further HLA imputation and detailed analysis of the association with HLA genes showed that two haplotypes, DRB1*13:02-DQB1*06:04 and DRB1*04:05-DQB1*04:01, were significantly associated in comparison with high-responders (HBsAb > 100 mIU/mL) for the two HB vaccines. In particular, HLA-DRB1*13:02-DQB1*06:04 haplotype is of great interest in the sense that it could only be detected by direct analysis of the high-responders in vaccination with Heptavax-II or Bimmugen. Compared with healthy controls, DRB1*13:02-DQB1*06:04 was significantly less frequent in high-responders when vaccinated with Heptavax-II, indicating that high antibody titers were less likely to be obtained with Heptavax-II. As Bimmugen and Heptavax-II tended to have high and low vaccine responses to DRB1*13:02, 15 residues were found in the Heptavax-II-derived antigenic peptide predicted to have the most unstable HLA-peptide binding. Further functional analysis of selected hepatitis B patients with HLA haplotypes identified in this study is expected to lead to an understanding of the mechanisms underlying liver disease. [ABSTRACT FROM AUTHOR]