Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines

Abstract

Vaccines are a key weapon against the COVID-19 pandemic caused by SARS-CoV-2. However, there are inter-individual differences in immune response to SARS-CoV-2 vaccines and genetic contributions to these differences have barely been investigated. Here, we performed genome-wide association study (GWAS) of antibody levels in 168 inactivated SARS-CoV-2 vaccine recipients. A total of 177 SNPs, corresponding to 41 independent loci, were identified to be associated with IgG, total antibodies or neutral antibodies. Specifically, the rs4543780, the intronic variant of FAM89A gene, was associated with total antibodies level and was annotated as a potential regulatory variant affecting gene expression of FAM89A, a biomarker differentiating bacterial from viral infections in febrile children. These findings might advance our knowledge of the molecular mechanisms driving immunity to SARS-CoV-2 vaccine.

Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population

“…Analysis of the impact of host genetic variation on SARS-CoV-2 vaccine-induced immunity has found associations between variant HLA alleles and variation in vaccine-induced antibody responses, vaccine breakthrough and vaccine side effects [ 63 , 64 ]. Small-scale pilot studies have also identified loci associated with variation in antibody responses following vaccination with an inactivated vaccine [ 65 ]. Our results, showing a significantly heritable response to both vaccine efficacy and reduced disease post challenge, suggest that the DO and related mouse populations can be used to complement human studies to understand the role of genetic variation in regulating vaccine responses.…”

Disarming the Sword of Damocles: Biomarkers and Susceptibilities to Spike Protein Diseases

“…These include MBL2 [32], ADAMTS13 [33], F8 [34] and PDGFRL [34], which are involved in clotting and have also been observed to be associated with acute Covid-19 severity. Our search reveals limited GWAS studies of long covid [35,36] or Covid-19 vaccine adverse events [37], though GWAS studies of SARS-CoV-2 vaccine antibody responses have been performed [38,39] and several mechanistic factors behind the differential vaccine response are identified [40]. Genetic correlates of vaccine adverse reactions have been studied in the context of Hepatitis B, measles, rubella, and other vaccines [41].…”