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

Gagne, Matthew; Corbett, Kizzmekia S; Flynn, Barbara J; Foulds, Kathryn E; Wagner, Danielle A; Andrew, Shayne F; Todd, John-Paul M; Honeycutt, Christopher Cole et al. · Cell · 2022

basic_science · Level V

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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 ID<sub>50</sub> 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-log<sub>10</sub> compared with control animals. In nasal swabs, sgRNA was reduced by 1-log<sub>10</sub>, 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.