Delta breakthrough infections elicit potent, broad and durable neutralizing antibody responses (preprint)

ABSTRACT

The SARS-CoV-2 Delta variant is currently responsible for most infections worldwide, including among vaccinated individuals. Although these latter infections lead to milder COVID-19 disease relative to unvaccinated subjects, the specificity and durability of antibody responses elicited by Delta 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 observed in subjects who were infected only or received only two doses of vaccine. We show that Delta breakthrough cases, subjects who were vaccinated after infection and individuals vaccinated three times (without infection) have serum neutralizing activity of comparable magnitude and breadth, indicating that multiple types of exposure or increased number of exposures to SARS-CoV-2 antigen(s) enhance antibody responses. Neutralization of SARS-CoV, however, was moderate, underscoring the importance of developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.