Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung.

Publication Type Academic Article
Authors Gagne M, Corbett K, Flynn B, Foulds K, Wagner D, Andrew S, Todd J, Honeycutt C, McCormick L, Nurmukhambetova S, Davis-Gardner M, Pessaint L, Bock K, Nagata B, Minai M, Werner A, Moliva J, Tucker C, Lorang C, Zhao B, McCarthy E, Cook A, Dodson A, Teng I, Mudvari P, Roberts-Torres J, Laboune F, Wang L, Goode A, Kar S, Boyoglu-Barnum S, Yang E, Shi W, Ploquin A, Doria-Rose N, Carfi A, Mascola J, Boritz E, Edwards D, Andersen H, Lewis M, Suthar M, Graham B, Roederer M, Moore I, Nason M, Sullivan N, Douek D, Seder R
Journal Cell
Volume 185
Issue 1
Pagination 113-130.e15
Date Published 12/03/2021
ISSN 1097-4172
Abstract 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.
DOI 10.1016/j.cell.2021.12.002
PubMed ID 34921774
PubMed Central ID PMC8639396
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