Six-month follow-up of antibody response to bivalent mRNA SARS-CoV-2 vaccine booster in healthcare workers

Healthcare workers (HCW) are at increased risk for SARS-CoV-2 exposure and infection and have been preferentially prioritised in vaccination campaigns. The present study aims to monitor vaccine-induced humoral immune response over a 6-month period in a cohort of 494 HCW who received a booster immunization with bivalent mRNA SARS-CoV-2 vaccines. Overall, the study sample displayed high anti-trimeric Spike IgG levels at baseline (prior vaccine administration), which increased one month after the bivalent booster but declined over the subsequent six months. Sex, type of vaccine, concomitant seasonal flu vaccination, and anti-N IgG seropositivity had no significant impact on antibody levels one-month post-vaccination, while higher antibody increase was seen in individuals with lower baseline immunity and older age groups. Sera from 45 HCWs were tested in neutralization assays against the BA.5 and XBB.1.5 subvariants. Almost all sera neutralized BA.5 before vaccination; 23 (51.1 %) neutralized XBB.1.5 before vaccination, rising to 35 (77.8 %) after six months. MNT against BA.5 was higher than against XBB.1.5 at both time points, and anti-trimeric S IgG levels correlated with MNT for both strains. In conclusion, the present study suggests significant pre-existing immunity, possibly from prior infections, asymptomatic exposure to SARS-CoV-2, and multiple vaccine doses. We found that individuals with lower baseline immunity exhibited a stronger and faster antibody response to vaccination, which was also beneficial in providing a broader antibody repertoire against newly circulating variants. Overall, these findings offer crucial insights for shaping future immunization policies in a population that remains at elevated risk.