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

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.
Competing Interests: Declaration of interests The Veesler laboratory has received an unrelated sponsored research agreement from Vir Biotechnology. A.C.W. and D.V. are named as inventors on patent applications filed by the University of Washington for SARS-CoV-2 and sarbecovirus receptor-binding domain nanoparticle vaccines. E.C. and D.C. are employees of Vir Biotechnology and may hold shares in Vir Biotechnology. H.Y.C. is a consultant for Merck, Pfizer, Ellume, and the Bill and Melinda Gates Foundation and has received support from Cepheid and Sanofi-Pasteur. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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