Cell reportsSep 30, 2026

Genetic differences in immune system and blood cell genes influence antibody protection from COVID-19 mRNA vaccines

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 1, 2026

Abstract

The HLA locus is associated with differential live-virus neutralizing and anti-SARS-CoV-2 spike antibodies after both the second and third vaccinations.

Genetic factors influencing antibody responses to COVID-19 vaccines vary among individuals.
Associations were observed between the HLA locus and levels of neutralizing antibodies after vaccination.
The HLA locus is linked to a reduced incidence of breakthrough infections following vaccination.
An association with antibody concentrations was replicated at the IGKV locus.
A new association was discovered at the HHEX locus, related to memory B-cell biology.

Simplified

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-naïve 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.

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Genetic differences in immune system and blood cell genes influence antibody protection from COVID-19 mRNA vaccines

Abstract

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