SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses

Alexandra C Walls; Kaitlin R Sprouse; John E Bowen; Anshu Joshi; Nicholas Franko; Mary Jane Navarro; Cameron Stewart; Elisabetta Cameroni; Matthew McCallum; Erin A Goecker; Emily J Degli-Angeli; Jenni Logue; Alex Greninger; Davide Corti; Helen Y Chu; David Veesler

doi:10.1016/j.cell.2022.01.011

SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses

Cell. 2022 Mar 3;185(5):872-880.e3. doi: 10.1016/j.cell.2022.01.011. Epub 2022 Jan 20.

Authors

Alexandra C Walls¹, Kaitlin R Sprouse², John E Bowen², Anshu Joshi², Nicholas Franko³, Mary Jane Navarro², Cameron Stewart², Elisabetta Cameroni⁴, Matthew McCallum², Erin A Goecker⁵, Emily J Degli-Angeli⁵, Jenni Logue³, Alex Greninger⁵, Davide Corti⁴, Helen Y Chu³, David Veesler⁶

Affiliations

¹ Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: acwalls@uw.edu.
² Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
³ Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA.
⁴ Humabs Biomed SA, a Subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
⁵ Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
⁶ Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu.

Abstract

Although infections among vaccinated individuals lead to milder COVID-19 symptoms relative to those in unvaccinated subjects, the specificity and durability of antibody responses elicited by breakthrough cases remain unknown. Here, we demonstrate that breakthrough infections induce serum-binding and -neutralizing antibody responses that are markedly more potent, durable, and resilient to spike mutations observed in variants than those in subjects who received only 2 doses of vaccine. However, we show that breakthrough cases, subjects who were vaccinated after infection, and individuals vaccinated three times have serum-neutralizing activity of comparable magnitude and breadth, indicating that an increased number of exposures to SARS-CoV-2 antigen(s) enhance the quality of antibody responses. Neutralization of SARS-CoV was moderate, however, underscoring the importance of developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.

Keywords: COVID-19; Delta variant; SARS-CoV-2; antibodies; breakthrough infection; neutralization; vaccine.

Abstract

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