2025-03-05 東京大学 ,慶應義塾大学 ,大阪大学,理化学研究所
<関連情報>
- https://www.k.u-tokyo.ac.jp/information/category/press/11453.html
- https://www.u-tokyo.ac.jp/content/400258463.pdf
- https://www.cell.com/cell-genomics/fulltext/S2666-979X(25)00039-4
生殖細胞系列変異とモザイク染色体変化はCOVID-19ワクチンの免疫原性に影響する Germline variants and mosaic chromosomal alterations affect COVID-19 vaccine immunogenicity
Kyuto Sonehara∙ Yoshifumi Uwamino, Ryunosuke Saiki∙ Seishi Ogawa∙ Yukinori Okada, Ho Namkoong
Cell Genomics Published:March 4, 2025
DOI:https://doi.org/10.1016/j.xgen.2025.100783
Graphical abstract
Highlights
•GWAS of vaccine immunogenicity reveals the contribution of MHC and IGH loci
•Protein QTL analysis identifies circulating immune regulators modulated by these loci
•Hematopoietic somatic alterations affecting MHC/IGH impair vaccine immunogenicity
•These hematopoietic somatic alterations confer infectious/immune disease risk
Summary
Vaccine immunogenicity is influenced by the vaccinee’s genetic background. Here, we perform a genome-wide association study of vaccine-induced SARS-CoV-2-specific immunoglobulin G (IgG) antibody titers and T cell immune responses in 1,559 mRNA-1273 and 537 BNT162b2 vaccinees of Japanese ancestry. SARS-CoV-2-specific antibody titers are associated with the immunoglobulin heavy chain (IGH) and major histocompatibility complex (MHC) locus, and T cell responses are associated with MHC. The lead variants at IGH contain a population-specific missense variant (rs1043109-C; p.Leu192Val) in the immunoglobulin heavy constant gamma 1 gene (IGHG1), with a strong decreasing effect (β = -0.54). Antibody-titer-associated variants modulate circulating immune regulatory proteins (e.g., LILRB4 and FCRL6). Age-related hematopoietic expanded mosaic chromosomal alterations (mCAs) affecting MHC and IGH also impair antibody production. MHC-/IGH-affecting mCAs confer infectious and immune disease risk, including sepsis and Graves’ disease. Impacts of expanded mosaic loss of chromosomes X/Y on these phenotypes were examined. Altogether, both germline and somatic mutations contribute to adaptive immunity functions.
