Long-term effects of HLA A*03:01 genotype on anti-SARS-CoV-2 Spike antibody levels following BNT162b2 vaccine

Introduction. We and others have recently reported that the remarkable variability of response to vaccines against SARS-CoV-2 is partially determined by the host genetic background. In particular, we found a significant association between the HLA A*03:01 allele and the increased anti-SARS-CoV-2 Spike antibody levels at two months following the first administration of the BNT162b2 vaccine. The present work aims to study the impact of the HLA A*03:01 genotype on antibody titers over time: before and after the booster dose administration. Material and Methods. From the database of 873 subjects analyzed in our previous study, we selected those with antibody titers measured at 8 and 12-14 months following the first dose of vaccine and with no serological evidence of SARS-CoV-2 infection at the time of antibody measurements. A bootstrapped multivariable piecewise linear mixed-effect regression model was applied to estimate the anti-S decay over time (modelled through a restricted cubic spline) before and after the booster was administered. To test differences among groups, an interaction term between time and the considered groups was introduced. Results. The analysis of longitudinal data revealed a decrease in antibody titers over time for both individuals carrying the HLA A*03:01 allele and non-carriers. It is noteworthy that subjects with the A*03:01 allele consistently maintained higher antibody titers than non-carriers. The difference between the two groups, however, narrowed as time progressed and it became non-significant about five months after the first dose. The booster dose administration drastically increased antibody levels in both groups, temporarily erasing any differences. However, starting from the 16th week after the booster administration, the differences became evident again. Finally, we confirmed that the effect of smoke on antibody levels remains constant over time and is erased only by booster dose administration. Conclusion. The booster dose significantly increased antibody levels and reduced the previously observed variability in vaccine response following the primary administration. While the effect of the HLA genotype on antibody titers tends to diminish over time, it remains present even after the booster dose. Regular booster dose administration may be particularly advantageous for particularly categories of individuals.