Multiple genetic control of anti-COVID-19 vaccine response by HLA locus (preprint)

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. We performed a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1,351 subjects. We confirmed the involvement of the HLA locus and observed significant associations with variants in HLA-A gene. In particular, the HLA-A*03:01 was the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. These results support the hypothesis that HLA genes modulate the response to anti-COVID-19 vaccines and highlight the need for genetic studies in diverse populations.

Spike-specific immune response induced by BNT162b2 mRNA vaccine in former COVID-19 patients and high responsive subjects (preprint)

Background: The worldwide escalation of Coronavirus Disease 2019 (COVID-19) has urgently required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of disease. The BNT162b2 (Pfizer–BioNTech) RNA-based vaccine confers 95% protection against COVID-19 by encoding a mutated isoform of SARS-CoV-2 full-length spike (S) protein. Objective: Here, we report the antigen-specific immune profile against SARS-CoV-2 S protein after vaccination with a single dose of BNT162b2 in order to define the immunological landscape required for an efficient response to the SARS-CoV-2 vaccine. Methods: We determined the levels of antibodies and antigen-specific B, T and NK-T cells against a recombinant GFP tagged SARS-CoV-2 S protein in subjects up to 20 days after injection of a single dose of BNT162b2 vaccine using a combined approach involving serological assays and flow cytometry analyses. Former COVID-19 patients have been also included in this study to evaluate the effect of vaccine after exposition to SARS-CoV-2. Results: The level of antigen-specific helper T-cells against SARS-CoV-2 S protein was reduced in subjects, low responsive or unresponsive to vaccination with respect to the highly responsive individuals, while the numbers of antigen-specific regulatory and cytotoxic T-cells were comparable. Of interest, in former COVID-19 patients, a single dose of BNT162b2 vaccine induced a significant increase of antibody production simultaneous with an antigen-specific B and NK-T cell response. Conclusion: Taken together, these results suggest that favorable immune profiles support the progression and an effective reaction to BNT162b2 vaccination.