Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in nonhuman primates is coincident with an anamnestic antibody response in the lower airway
Author:
Gagne MatthewORCID, Corbett Kizzmekia S., Flynn Barbara J., Foulds Kathryn E., Wagner Danielle A., Andrew Shayne F., Todd John-Paul M., Honeycutt Christopher Cole, McCormick Lauren, Nurmukhambetova Saule T., Davis-Gardner Meredith E., Pessaint Laurent, Bock Kevin W., Nagata Bianca M., Minai Mahnaz, Werner Anne P., Moliva Juan I., Tucker Courtney, Lorang Cynthia G., Zhao Bingchun, McCarthy Elizabeth, Cook Anthony, Dodson Alan, Mudvari Prakriti, Roberts-Torres Jesmine, Laboune Farida, Wang Lingshu, Goode Adrienne, Kar Swagata, Boyoglu-Barnum Seyhan, Yang Eun Sung, Shi Wei, Ploquin Aurélie, Doria-Rose Nicole, Carfi Andrea, Mascola John R., Boritz Eli A., Edwards Darin K., Andersen Hanne, Lewis Mark G., Suthar Mehul S., Graham Barney S., Roederer Mario, Moore Ian N., Nason Martha C., Sullivan Nancy J., Douek Daniel C., Seder Robert A.
Abstract
ABSTRACTmRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year in blood, upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody binding titers also decreased in bronchoalveolar lavage (BAL). Four days after challenge, virus was unculturable in BAL and subgenomic RNA declined ∼3-log10 compared to control animals. In nasal swabs, sgRNA declined 1-log10 and virus remained culturable. Anamnestic antibody responses (590-fold increase) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.
Publisher
Cold Spring Harbor Laboratory
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