The humoral and cellular response tomRNA SARS‐CoV‐2 vaccine is influenced byHLApolymorphisms

Abstract

Host genetic variability contributes to susceptibility to SARS‐CoV‐2 infection and COVID‐19 evolution and the role of HLA system has not clearly emerged, suggesting the involvement of other factors. Studying response to vaccination with Spyke protein mRNA represents an ideal model to highlight whether the humoral or cellular responses are influenced by HLA. Four hundred and sixteen workers, vaccinated with Comirnaty beginning 2021, were selected within the Azienda Ospedaliera Universitaria “Città della Salute e della Scienza di Torino.” The humoral response was determined with the LIAISON® kit, while the analysis of the cellular response was performed with the Quantiferon SARS‐CoV‐2 assay, for the S1 (receptor‐binding domain; Ag1) and S1 and S2 (Ag2) subunits of the Spyke protein. Six HLA loci were typed by next‐generation sequencing. Associations between HLA and vaccine response were performed with univariate and multivariate analyses. An association was found betweenA*03:01,B*40:02andDPB1*06:01and high antibody concentration and betweenA*24:02,B*08:01andC*07:01and low humoral responses. The haplotypeHLA‐A*01:01 ~ B1*08:01 ~ C*07:01 ~ DRB1*03:01 ~ DQB1*02:01conferred an increased risk of low humoral response. Considering cellular responses, 50% of the vaccinated subjects responded against Ag1 and 59% against Ag2. Carriers ofDRB1*15:01displayed a higher cellular response both to Ag1 and Ag2 compared to the rest of the cohort. Similarly,DRB1*13:02predisposed to a robust cellular response to Ag1 and Ag2, whileDRB1*11:04showed an opposite trend. Cellular and humoral responses to Comirnaty are influenced by HLA. Humoral response is mainly associated to class I alleles, withA*03:01, previously associated to protection against severe COVID‐19, and response to vaccination, standing out. Cellular response predominantly involves class II alleles, withDRB1*15:01andDPB1*13:01prevailing. Affinity analysis for Spyke peptides is generally in line with the association results.