Importance of HBsAg recognition by HLA molecules as revealed by responsiveness to different hepatitis B vaccines

Importance of HBsAg recognition by HLA molecules as revealed by responsiveness to different hepatitis B vaccines

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...

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Autores principales: Nao Nishida, Masaya Sugiyama, Jun Ohashi, Yosuke Kawai, Seik-Soon Khor, Sohji Nishina, Kazumi Yamasaki, Hirohisa Yazaki, Kaori Okudera, Akihiro Tamori, Yuichiro Eguchi, Aiko Sakai, Keisuke Kakisaka, Hiromi Sawai, Takayo Tsuchiura, Miyuki Ishikawa, Keisuke Hino, Ryo Sumazaki, Yasuhiro Takikawa, Tatsuo Kanda, Osamu Yokosuka, Hiroshi Yatsuhashi, Katsushi Tokunaga, Masashi Mizokami
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/bc153c9e54d248538490613f659d2d46
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Sumario: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.

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