PuSH - Publication Server of Helmholtz Zentrum München

Puzek, B. ; Wratil, P.R.* ; Janke, C.* ; Thi, T.G.L.* ; Rubio-Acero, R.* ; Lupoli, G.* ; Schoof, I.C.* ; Stern, M.* ; Zhelyazkova, A.* ; Rech, J.* ; Chouke, A.* ; Koletzko, B.* ; Wieser, A.* ; Torok, H.P.* ; Castelletti, N. ; Keppler, O.T.* ; Geldmacher, C.* ; Hornung, V.* ; Zeggini, E. ; Adorjan, K.* ; Hoelscher, M. ; Koletzko, S.* ; Kim-Hellmuth, S.

Genetic variation in HLA, IGKV, and HHEX loci influences mRNA vaccine-induced humoral protection against COVID-19.

Cell Rep. 45:117981 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Humoral immune responses to COVID-19 vaccination vary widely across individuals, yet the genetic determinants of functional antibody protection beyond binding antibodies after two immunizations remain poorly understood. We performed genome-wide association studies on antigen-specific antibody concentrations and live-virus neutralization activities after two and three vaccine doses in two German cohorts of SARS-CoV-2 infection-na & imath;& uml;ve individuals (RisCoin study n = 2,877; KoCo19 study n = 1,654). We found the HLA locus to be associated with differential live-virus neutralizing and anti-SARS-CoV-2 spike antibodies after both the second and third vaccinations. Consistent with its effect on third-dose neutralization, the HLA was additionally associated with a reduced incidence of breakthrough infection. We further replicated an association with antibody concentrations at the IGKV locus and discovered an association at the HHEX locus, implicating pathways linked to memory B-cell biology. Together, these findings reveal host genetic factors shaping neutralizing immunity and vaccine-induced protection against infection, with implications for personalized vaccination strategies.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Association
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 45, Issue: 10, Pages: , Article Number: 117981 Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genetics (ITG)
Research Unit Global Health (UGH)
Institute of Radiation Medicine (IRM)
Grants T1DGC study
Juvenile Diabetes Research Foundation International (JDRF)
National Institute of Child Health and Human Development (NICHD)
National Human Genome Research Institute (NHGRI)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)