Associations between Allelic Variants of the Human IgH 3′ Regulatory Region 1 and the Immune Response to BNT162b2 mRNA Vaccine

Colucci, Mattia; De Santis, Elisabetta; Totti, Beatrice; Miroballo, Mattia; Tamiro, Francesco; Rossi, Giovanni; Piepoli, Ada; De Vincentis, Gabriella; Greco, Antonio; Mangia, Alessandra; Cianci, Rossella; Di Mauro, Lazzaro; Miscio, Giuseppe; Giambra, Vincenzo

The escalation of Coronavirus disease 2019 (COVID-19) has required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2-associated (SARS-CoV-2), which is the causative agent of the disease. Here, we determined the levels of antibodies, antigen-specific B cells, against a recombinant GFP-tagged SARS-CoV-2 spike (S) protein and total T and NK cell subsets in subjects up to 20 days after the injection of the BNT162b2 (Pfizer–BioNTech) vaccine using a combined approach of serological and flow cytometry analyses. In former COVID-19 patients and highly responsive individuals, a significant increase of antibody production was detected, simultaneous with an expansion of antigen-specific B cell response and the total number of NK-T cells. Additionally, through a genetic screening of a specific polymorphic region internal to the 3’ regulatory region 1 (3’RR1) of human immunoglobulin constant-gene (IgH) locus, we identified different single-nucleotide polymorphic (SNP) variants associated with either highly or lowly responsive subjects. Taken together, these results suggest that favorable genetic backgrounds and immune profiles support the progression of an effective response to BNT162b2 vaccination.