Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates

Corbett, K. S.; Nason, M.; Flach, B.; Gagne, M.; O'Connell, S.; Johnston, T.; Shah, S. N.; Edara, V. V.; Floyd, K.; Lai, L.; McDanal, C.; Francica, J.; Flynn, B.; Wu, K.; Choi, A.; Koch, M.; Abiona, O. M.; Werner, A. P.; Alvarado, G. S.; Andrew, S. F.; Donaldson, M. M.; Fintzi, J.; Flebbe, D.; Lamb, E.; Noe, A.; Nurmukhambetova, S.; Provost, S.; Cook, A.; Dodson, A.; Faudree, A.; Greenhouse, J.; Kar, S.; Pessaint, L.; Porto, M.; Steingrebe, K.; Valentin, D.; Zouantcha, S.; Bock, K.; Mahnaz, M.; Nagata, B.; Moliva, J. I.; van de Wetering, R.; Boyoglu-Barnum, S.; Leung, K.; Shi, W.; Yang, E. S.

doi:10.1101/2021.04.20.440647

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bioRxiv · 10.1101/2021.04.20.440647

Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates

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Abstract

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 g of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naive hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP. One-Sentence SummarymRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

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Corbett, K. S., Nason, M., Flach, B., Gagne, M., O'Connell, S., Johnston, T., Shah, S. N., Edara, V. V., Floyd, K., Lai, L., McDanal, C., Francica, J., Flynn, B., Wu, K., Choi, A., Koch, M., Abiona, O. M., Werner, A. P., Alvarado, G. S., Andrew, S. F., Donaldson, M. M., Fintzi, J., Flebbe, D., Lamb, E., Noe, A., Nurmukhambetova, S., Provost, S., Cook, A., Dodson, A., Faudree, A., Greenhouse, J., Kar, S., Pessaint, L., Porto, M., Steingrebe, K., Valentin, D., Zouantcha, S., Bock, K., Mahnaz, M., Nagata, B., Moliva, J. I., van de Wetering, R., Boyoglu-Barnum, S., Leung, K., Shi, W., Yang, E. S.. 2021-04-21. Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates. https://doi.org/10.1101/2021.04.20.440647

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