# Immunogenicity and Breakthrough Outcomes of mRNA Booster Strategies Among Healthcare Workers During the BA.1/BA.2 Omicron Surge

## TL;DR

This study compares how well different mRNA booster vaccine strategies protect healthcare workers during the Omicron surge, finding that while boosters restore antibody levels, they vary in preventing infections.

## Contribution

The study provides real-world evidence on the effectiveness of various mRNA booster strategies during the BA.1/BA.2 Omicron wave.

## Key findings

- mRNA boosters restored neutralizing antibody levels to over 97% across all regimens.
- The A-P-P regimen had the highest breakthrough infection risk (84.2%) compared to others.
- Antibody titers alone are insufficient for evaluating protection against Omicron.

## Abstract

Throughout the 2019 coronavirus disease pandemic, various vaccine regimens were implemented. Real-world data comparing their effectiveness during the BA.1/BA.2 Omicron wave remain limited. We prospectively enrolled healthcare workers who had completed two doses of mRNA or ChAdOx1 (A) vaccine and received an mRNA vaccine booster (BNT162b2 (P) or mRNA-1273 (M)). Neutralizing antibody levels were measured 6 months after the primary vaccinations and 1 month post-booster vaccination using a surrogate virus neutralization assay. Breakthrough infections were identified through institutional surveillance and the national reporting system. Among 318 participants (P-P-P: 71; A-A-P: 205; A-P-P: 19; M-M-M: 23), pre-booster neutralizing activity was lowest in the ChAdOx1-primed groups. One month post-booster vaccination, the neutralizing activity exceeded 97% across all regimens. The cumulative incidence of breakthrough infection varied significantly from 43.7% (P-P-P) to 84.2% (A-P-P). In adjusted Cox models, A-P-P showed the highest infection risk (HR 2.99, 95% CI 1.65–5.42). In summary, mRNA boosters restored neutralizing activity, but during the early BA.1/BA.2 Omicron wave they were less effective in preventing infections regardless of disease severity. Therefore, antibody titers alone are insufficient for evaluating protection, underscoring the need for continuous monitoring to support timely policy decisions during epidemic surges.