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.

doi:10.1101/2021.10.23.465542

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bioRxiv · 10.1101/2021.10.23.465542

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

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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. 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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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.. 2021-10-24. 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. https://doi.org/10.1101/2021.10.23.465542

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