Multiple genetic control of anti-COVID-19 vaccine response by HLA locus

Since the beginning of the anti-COVID-19 vaccination campaign, it has become evident that vaccinated subjects exhibit considerable inter-individual variability in the response to the vaccine that could be partly explained by host genetic factors. A recent study reported that the immune response elicited by the Oxford-AstraZeneca vaccine in individuals from the United Kingdom was influenced by a specific allele of the human leukocyte antigen gene HLA-DQB1. We performed a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1,351 subjects. We confirmed the involvement of the HLA locus and observed significant associations with variants in HLA-A gene. In particular, the HLA-A*03:01 was the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. These results support the hypothesis that HLA genes modulate the response to anti-COVID-19 vaccines and highlight the need for genetic studies in diverse populations.