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- Title
Importance of HBsAg recognition by HLA molecules as revealed by responsiveness to different hepatitis B vaccines.
- Authors
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
- 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.
- Subjects
HEPATITIS B vaccines; GENOTYPES; GENOMES; HAPLOTYPES; FUNCTIONAL analysis
- Publication
Scientific Reports, 2021, Vol 11, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-021-82986-8