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

• Published in: Cell Vol. 185; no. 5; pp. 872 - 880.e3
• Main Authors: Walls, Alexandra C., Sprouse, Kaitlin R., Bowen, John E., Joshi, Anshu, Franko, Nicholas, Navarro, Mary Jane, Stewart, Cameron, Cameroni, Elisabetta, McCallum, Matthew, Goecker, Erin A., Degli-Angeli, Emily J., Logue, Jenni, Greninger, Alex, Corti, Davide, Chu, Helen Y., Veesler, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.03.2022
• Subjects: antibodies; antigens; breakthrough infection; COVID-19; COVID-19 infection; Delta variant; durability; neutralization; pandemic; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; vaccine; vaccines; COVID-19; SARS-CoV-2; vaccine; neutralization; breakthrough infection; Delta variant; antibodies
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2022.01.011

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. [Display omitted] •Breakthrough infections induce potent neutralizing antibody responses•Number of exposures (infection or vaccination) correlates with potency and breadth•Three-dose vaccination improves neutralization of the SARS-CoV-2 Omicron variant•SARS-CoV-2 infection or vaccination elicit moderate neutralization of SARS-CoV Individuals with breakthrough COVID-19 infections, previously infected/vaccinated individuals, and those vaccinated thrice have potent serum-binding and -neutralizing antibody responses against variants of concern, including Omicron. Neutralization of SARS-CoV, however, was moderate, thus urging the need for developing broad vaccines for pandemic preparedness.