Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung
2022
Gagne, Matthew | 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 | Teng, I-Ting | 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.
mRNA-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. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and 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 Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log₁₀ compared with control animals. In nasal swabs, sgRNA was reduced by 1-log₁₀, and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) 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.
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