Variant-specific and cross-reactive antibody responses following COVID-19 booster vaccinations and SARS-CoV-2 breakthrough infections
- 1Center for Virology, Medical University of Vienna
Abstract
SARS-CoV-2 has evolved into several genetic variants, all bearing mutations that reduce antibody binding and affect vaccine and treatment effectiveness. Updated COVID-19 vaccines, including bivalent formulations (wild type [WT]/BA.1 or WT/BA.5) and more recent monovalent versions targeting emerging variants such as XBB.1.5, JN.1, KP.2 or LP.8.1, were developed to broaden protection. However, immune imprinting may limit the induction of neutralizing antibodies against strains that differ significantly, even after receiving several variant-specific boosters. A deeper understanding of how booster vaccination reshapes antibody specificity remains essential for rational vaccine design. We examined the antibody response to a bivalent WT/BA.5 booster, focusing on antibody levels and neutralization. Serum samples collected before and after a fourth dose of monovalent WT or bivalent (WT/BA.5) mRNA vaccines were compared with sera from individuals after primary WT infections and Omicron BA.1, BA.2, or BA.5 breakthrough infections. We found that both monovalent and bivalent boosters significantly increased IgG and neutralizing antibodies, but breakthrough infections induced broader cross-reactive responses. Depletion experiments revealed that booster-induced immunity was predominantly mediated by cross-reactive antibodies, with the highest levels after breakthrough infections and the lowest after a primary WT infection. These findings provide functional insights into the antibody specificities associated with imprinting effects following variant-adapted booster vaccination.
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BibTeX
@article{meditsweiss2026variantspecific,
title = {{Variant-specific and cross-reactive antibody responses following COVID-19 booster vaccinations and SARS-CoV-2 breakthrough infections}},
author = {Iris Medits-Weiss and Dominik Moll and David N. Springer and Stephan W. Aberle and Judith H. Aberle and Karin Stiasny},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62635-8},
url = {https://doi.org/10.1038/s41598-026-62635-8},
note = {CC BY},
}
RIS
TY - JOUR
TI - Variant-specific and cross-reactive antibody responses following COVID-19 booster vaccinations and SARS-CoV-2 breakthrough infections
AU - Iris Medits-Weiss
AU - Dominik Moll
AU - David N. Springer
AU - Stephan W. Aberle
AU - Judith H. Aberle
AU - Karin Stiasny
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62635-8
UR - https://doi.org/10.1038/s41598-026-62635-8
AB - SARS-CoV-2 has evolved into several genetic variants, all bearing mutations that reduce antibody binding and affect vaccine and treatment effectiveness. Updated COVID-19 vaccines, including bivalent formulations (wild type [WT]/BA.1 or WT/BA.5) and more recent monovalent versions targeting emerging variants such as XBB.1.5, JN.1, KP.2 or LP.8.1, were developed to broaden protection. However, immune imprinting may limit the induction of neutralizing antibodies against strains that differ significantly, even after receiving several variant-specific boosters. A deeper understanding of how booster vaccination reshapes antibody specificity remains essential for rational vaccine design. We examined the antibody response to a bivalent WT/BA.5 booster, focusing on antibody levels and neutralization. Serum samples collected before and after a fourth dose of monovalent WT or bivalent (WT/BA.5) mRNA vaccines were compared with sera from individuals after primary WT infections and Omicron BA.1, BA.2, or BA.5 breakthrough infections. We found that both monovalent and bivalent boosters significantly increased IgG and neutralizing antibodies, but breakthrough infections induced broader cross-reactive responses. Depletion experiments revealed that booster-induced immunity was predominantly mediated by cross-reactive antibodies, with the highest levels after breakthrough infections and the lowest after a primary WT infection. These findings provide functional insights into the antibody specificities associated with imprinting effects following variant-adapted booster vaccination.
SN - 2045-2322
ER -