Antibody Responses to SARS-CoV-2 Variants are Significantly Increased Following BNT162b2 Vaccine Boost in SARS-CoV-2 Exposed and Naïve Individuals

Emergence of SARS-Cov-V2 variants during the Covid-19 pandemic has raised concerns; understanding the impact of exposure and vaccination on the effectiveness of immune responses to variants of concern is an urgent priority. From a large cohort of healthcare workers followed serologically since April 2020 we purposively sampled 20 with and 25 without confirmed previous SARS-CoV-2 infection. All 45 had received two doses of the Pfizer BTN162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titres against lineage A, B.1 and B.1.351 variants were measured using enzyme immunoassays and a pseudotype neutralization assay, respectively. We observed significant increases in ID50 against lineage A, B.1.351 and P.1 variants with increasing antigenic exposure (either through vaccination or natural infection) and this superiority was confirmed in neutralization assays using a fixed dilution of each serum. The impact of antigenic exposure was even more evident in enzyme immunoassays measuring spike-specific IgG antibody levels. Our data show that multiple exposures (vaccine or natural infection) when utilizing a delayed booster significantly expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants, suggesting that additional boosts would be highly beneficial in reducing the impact of future waves of SARS-CoV-2 including those related to the variants.