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

• Published in: Scientific reports 2021-03, Vol.11 (1), p.3703-3703, Article 3703
• Main 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, Yokosuka, Osamu, Yatsuhashi, Hiroshi, Tokunaga, Katsushi, Mizokami, Masashi
• Format: Article
• Language: English
• Subjects: 631/208; 692/4020; 692/499; 692/53; 692/699; Drb1 protein; Genome-wide association studies; Genomes; Genotypes; Haplotypes; Hepatitis; Hepatitis B; Hepatitis B surface antigen; Histocompatibility antigen HLA; Humanities and Social Sciences; Immunization; Liver diseases; multidisciplinary; Peptides; Science; Science (multidisciplinary); Vaccines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-82986-8

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.