Journal Article

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

Andrew, Shayne F, Shi, Wei, Douek, Daniel C, Yang, Eun Sung, Davis-Gardner, Meredith E, Boyoglu-Barnum, Seyhan, Boritz, Eli A, Mascola, John R, Goode, Adrienne, Dodson, Alan, Carfi, Andrea, Sullivan, Nancy J, Nurmukhambetova, Saule T, Flynn, Barbara J, Corbett, Kizzmekia S, Graham, Barney S, Roederer, Mario, Todd, John-Paul M, Roberts-Torres, Jesmine, Pessaint, Laurent, McCormick, Lauren, Mudvari, Prakriti, Minai, Mahnaz, McCarthy, Elizabeth, Ploquin, Aurélie, Nagata, Bianca M, Lewis, Mark G, Wang, Lingshu, Suthar, Mehul S, Laboune, Farida, Gagne, Matthew, Zhao, Bingchun, Cook, Anthony, Nason, Martha C, Tucker, Courtney, Andersen, Hanne, Moore, Ian N, Werner, Anne P, Moliva, Juan I, Foulds, Kathryn E, Doria-Rose, Nicole, Wagner, Danielle A, Seder, Robert A, Bock, Kevin W, Kar, Swagata, Edwards, Darin K, Lorang, Cynthia G, Honeycutt, Christopher Cole

2021

Overview

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. 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 ID 50 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-log 10 compared to control animals. In nasal swabs, sgRNA declined 1-log 10 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.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. 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 ID 50 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-log 10 compared to control animals. In nasal swabs, sgRNA declined 1-log 10 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
• Subject: Immunology