Association study of HLA with the kinetics of SARS-CoV-2 spike specific IgG antibody responses to BNT162b2 mRNA vaccine

Abstract

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer-BioNTech), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4+ & CD8+ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (P = 0.017; Odd ratio (OR) 2.80, 95%Confidence interval (CI) 1.05–7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2 while DQB1*06:01:01:01 (P = 0.028, OR 0.27, 95%CI 0.05–0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (P = 0.058; OR 0.42, 95%CI 0.15–1.16), B*52:01:01 (P = 0.031; OR 0.38, 95%CI 0.14–1.03), DQA1*03:02:01 (P = 0.028; OR 0.39, 95%CI 0.15–1.00) and DPB1*02:01:02 (P = 0.024; OR 0.45, 95%CI 0.21–0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination.

Associations of HLA polymorphisms with anti-SARS-CoV-2 spike and neutralizing antibody titers in Japanese rheumatoid arthritis patients vaccinated with BNT162b2

“…However, in silico DRB1*15:01 was predicted to have a higher number of strong binding peptides derived from the entire sequence of the SARS-CoV-2 S protein [19]. HLA associations with anti-SARS-CoV-2 S Abs had also been analyzed in 100 Japanese hospital workers [18] and DQA1:03:03 was reported to be associated with production of greater amounts of anti-SARS-CoV-2 S Abs. In that study, the association of DRB1*12:01 with higher levels of anti-SARS-CoV-2 S Abs was not reported.…”

“…However, few studies on the association of HLA with levels of anti-SARS-CoV-2 S Abs have been reported [18,19]. Hence, we investigated the association of HLA polymorphisms with levels of anti-SARS-CoV-2 S-specific or neutralizing Abs in vaccinated RA patients in Japan.…”