VaccineJul 31, 2025

Six-month antibody levels after bivalent COVID-19 mRNA booster in healthcare workers

Updated Feb 17, 2026

Abstract

494 healthcare workers were monitored for their immune response after receiving a bivalent mRNA SARS-CoV-2 booster vaccine over a six-month period.

High levels of anti-trimeric Spike IgG were observed at baseline, which increased one month post-vaccination but declined over the following six months.
Sex, type of vaccine, seasonal flu vaccination, and existing anti-N IgG seropositivity did not significantly affect antibody levels one month after vaccination.
Individuals with lower baseline immunity and older age groups showed a greater increase in antibody levels following vaccination.
Neutralization assays indicated that nearly all sera neutralized the BA.5 subvariant before vaccination, with 51.1% neutralizing the XBB.1.5 subvariant prior to vaccination, increasing to 77.8% after six months.
Higher neutralization titers against BA.5 compared to XBB.1.5 were observed at both time points.
The findings suggest significant pre-existing immunity in the cohort, potentially from prior infections or multiple vaccinations.

Simplified

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.

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Competing interests

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giorgio Fedele reports financial support was provided by Progetto R.I.P.r.E.I. 2022. Tiziana Lazzarotto reports financial support was provided by NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging infectious Diseases. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

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Competing interests

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