# Longitudinal SARS‐CoV‐2 Antibody Response in Healthcare Workers: Benefit of Prior Infection and Heterologous Boosting on Anti‐Spike IgG Immunity

## TL;DR

This study compares immune responses to mRNA and adenoviral vector vaccines in healthcare workers, showing how prior infection and boosters affect antibody levels.

## Contribution

The study reveals how prior SARS-CoV-2 infection and booster vaccination influence antibody responses based on vaccine type.

## Key findings

- mRNA-vaccinated individuals had higher anti-S IgG titres than Ad-vector recipients after booster.
- Ad-vector recipients showed superior neutralising capacity compared to mRNA recipients.
- Prior SARS-CoV-2 infection impacted antibody levels differently based on vaccine type and timing.

## Abstract

Different COVID‐19 vaccine platforms elicit variable immune responses, influenced by prior infection and booster vaccination. We aimed to compare the humoral immune responses elicited by mRNA and adenoviral vector (Ad‐vector) COVID‐19 vaccines in hospital employees and to assess the possible impact of prior SARS‐CoV‐2 infection on these responses.

We performed a prospective observational cohort study by recruiting employees of the Universitair Ziekenhuis Brussel who were vaccinated with an mRNA or Ad‐vector vaccine. We assessed anti‐spike (S) IgG and neutralising capacity at 1, 6 and 12 months (post‐mRNA booster). Anti‐S and anti‐NCP IgG were measured by chemiluminescent microparticle immunoassay, and neutralising capacity was assessed using Genscript's cPASS. Non‐parametric group comparisons used the Mann–Whitney U test, complemented by multiple linear regression.

Following RVR, mRNA‐vaccinated individuals (n = 380) exhibited higher anti‐S IgG titres and neutralising capacity compared to those who received Ad‐vector vaccines (n = 200). After the booster, anti‐spike IgG remained higher in mRNA‐vaccinated individuals than in Ad‐vector recipients (q < 0.001); Ad‐vector vaccinated individuals showed superior neutralising capacity. Natural SARS‐CoV‐2 infection prior to vaccination had varying impact on anti‐S IgG and neutralising capacity, depending on vaccination type and time points.

Our findings underscore that both vaccine platforms and prior infections shape the magnitude and quality of the humoral immune response, highlighting the importance of considering priming strategy, booster design and hybrid immunity when optimising COVID‐19 vaccination schedules for durable protection.