Evolution of antibody immunity following Omicron BA.1 breakthrough infection

Chengzi I. Kaku, Tyler N. Starr, Panpan Zhou, Haley L. Dugan, Paul Khalifé, Ge Song, Elizabeth R. Champney, Daniel W. Mielcarz, James C. Geoghegan, Dennis R. Burton, Raiees Andrabi, Jesse D. Bloom and Laura M. Walker ()
Additional contact information
Chengzi I. Kaku: Adimab, LLC
Tyler N. Starr: Fred Hutchinson Cancer Center
Panpan Zhou: The Scripps Research Institute
Haley L. Dugan: Adimab, LLC
Paul Khalifé: Adimab, LLC
Ge Song: The Scripps Research Institute
Elizabeth R. Champney: Adimab, LLC
Daniel W. Mielcarz: Geisel School of Medicine
James C. Geoghegan: Adimab, LLC
Dennis R. Burton: The Scripps Research Institute
Raiees Andrabi: The Scripps Research Institute
Jesse D. Bloom: Fred Hutchinson Cancer Center
Laura M. Walker: Invivyd Inc.

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Understanding the longitudinal dynamics of antibody immunity following heterologous SAR-CoV-2 breakthrough infection will inform the development of next-generation vaccines. Here, we track SARS-CoV-2 receptor binding domain (RBD)-specific antibody responses up to six months following Omicron BA.1 breakthrough infection in six mRNA-vaccinated individuals. Cross-reactive serum neutralizing antibody and memory B cell (MBC) responses decline by two- to four-fold through the study period. Breakthrough infection elicits minimal de novo Omicron BA.1-specific B cell responses but drives affinity maturation of pre-existing cross-reactive MBCs toward BA.1, which translates into enhanced breadth of activity across other variants. Public clones dominate the neutralizing antibody response at both early and late time points following breakthough infection, and their escape mutation profiles predict newly emergent Omicron sublineages, suggesting that convergent antibody responses continue to shape SARS-CoV-2 evolution. While the study is limited by our relatively small cohort size, these results suggest that heterologous SARS-CoV-2 variant exposure drives the evolution of B cell memory, supporting the continued development of next-generation variant-based vaccines.

Date: 2023
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DOI: 10.1038/s41467-023-38345-4

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