Journal Article

Human leukocyte antigen variants associate with BNT162b2 mRNA vaccine response

Esposito, Martina, De Vincentis, Gabriella, Brugnoni, Raffaella, Croci, Susanna, Piepoli, Ada, Fratelli, Maddalena, Dragani, Tommaso A., Carella, Massimo, Miscio, Giuseppe, Bruttini, Mirella, Perna, Rita, Minnai, Francesca, Copetti, Massimiliano, Benvenuto, Mario, Fallerini, Chiara, Baggi, Fulvio, Renieri, Alessandra, D’Addetta, Paola, Baldassarri, Margherita, Mantegazza, Renato E., Cavalcante, Paola, Colombo, Francesca, Corsini, Elena Maria Grazia, Ciusani, Emilio, Andreetta, Francesca

2024

Overview

Background 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 . Methods We carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above. Results Our study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A , HLA-DQA1 , and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. Other alleles, from both major histocompatibility complex class I and II are significantly associated with antibody levels. Conclusions These results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies in diverse populations and for functional studies aimed to elucidate the relationship between HLA-A*03:01 and CD8+ cell response upon Pfizer-BioNTech vaccination. Plain language summary It is known that people respond differently to vaccines. It has been proposed that differences in their genes might play a role. We studied the individual genetic makeup of 1351 people from Italy to see if there was a link between their genes and how well they responded to the BNT162b2 mRNA COVID-19 vaccine. We discovered certain genetic differences linked to higher levels of protection in those who got the vaccine. Our findings suggest that individual’s genetic characteristics play a role in vaccine response. A larger population involving diverse ethnic backgrounds will need to be studied to confirm the generalizability of these findings. Better understanding of this could facilitate improved vaccine designs against new SARS-CoV-2 variants. Esposito et al. investigate the genetic basis of response to BNT162b2 mRNA COVID-19 vaccine in 1351 Italian subjects. They find variants in the human leukocyte antigen locus significantly associate with serum anti-SARS-CoV-2 antibody levels, after vaccination.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Portfolio
• Subject: 45/43 / 631/208/205/2138 / 692/699/255/2514 / Age / Antibodies / Antigens / COVID-19 vaccines / Ethics / Genetic diversity / Genomes / Genotype & phenotype / Leukocytes / Medicine / Medicine & Public Health / Population genetics / Principal components analysis / Quality control / Regression analysis / Serology / Severe acute respiratory syndrome coronavirus 2 / Software / Values / Variables