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
Gagne, M.; Corbett, K. S.; Flynn, B. J.; Foulds, K. E.; Wagner, D. A.; Andrew, S. F.; Todd, J.-P. M.; Honeycutt, C. C.; McCormick, L.; Nurmukhambetova, S. T.; Davis-Gardner, M. E.; Pessaint, L.; Bock, K. W.; Nagata, B. M.; Minai, M.; Werner, A. P.; Moliva, J. I.; Tucker, C.; Lorang, C. G.; Zhao, B.; McCarthy, E.; Cook, A.; Dodson, A.; Mudvari, P.; Roberts-Torres, J.; Laboune, F.; Wang, L.; Goode, A.; Kar, S.; Boyoglu-Barnum, S.; Yang, E. S.; Shi, W.; Ploquin, A.; Doria-Rose, N.; Carfi, A.; Mascola, J. R.; Boritz, E. A.; Edwards, D. K.; Andersen, H.; Lewis, M. G.; Suthar, M. S.; Graham, B. S.;
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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 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.
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