mRNA-1273 vaccination protects against SARS-CoV-2 elicited lung inflammation in non-human primates

Waickman, A. T.; Victor, K.; Newell, K. L.; Li, T. L.; Friberg, H.; Foulds, K.; Roederer, M.; Bolton, D. L.; Currier, J. R.; Seder, R.

doi:10.1101/2021.12.24.474132

bioRxiv · 10.1101/2021.12.24.474132

mRNA-1273 vaccination protects against SARS-CoV-2 elicited lung inflammation in non-human primates

Waickman, A. T.·Victor, K.·Newell, K. L.·Li, T. L.·Friberg, H.·Foulds, K.·Roederer, M.·Bolton, D. L.·Currier, J. R.·Seder, R.

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Abstract

Vaccine-elicited SARS-CoV-2 antibody responses are an established correlate of protection against viral infection in humans and non-human primates. However, it is less clear that vaccine-induced immunity is able to limit infection-elicited inflammation in the lower respiratory tract. To assess this, we collected bronchoalveolar lavage fluid samples post-SARS-CoV-2 strain USA-WA1/2020 challenge from rhesus macaques vaccinated with mRNA-1273 in a dose-reduction study. Single-cell transcriptomic profiling revealed a broad cellular landscape 48 hours post-challenge with distinct inflammatory signatures that correlated with viral RNA burden in the lower respiratory tract. These inflammatory signatures included phagocyte-restricted expression of chemokines such as CXCL10 (IP10) and CCL3 (MIP-1A) and the broad expression of interferon-induced genes such as MX1, ISG15, and IFIT1. Induction of these inflammatory profiles was suppressed by prior mRNA-1273 vaccination in a dose-dependent manner, and negatively correlated with pre-challenge serum and lung antibody titers against SARS-CoV-2 spike. These observations were replicated and validated in a second independent macaque challenge study using the B.1.351/beta-variant of SARS-CoV-2. These data support a model wherein vaccine-elicited antibody responses restrict viral replication following SARS-CoV-2 exposure, including limiting viral dissemination to the lower respiratory tract and infection-mediated inflammation and pathogenesis. One Sentence SummarySingle cell RNA sequencing analysis demonstrates that mRNA-1273 vaccination limits the development of lower respiratory tract inflammation in SARS-CoV-2 challenged rhesus macaques

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Waickman, A. T., Victor, K., Newell, K. L., Li, T. L., Friberg, H., Foulds, K., Roederer, M., Bolton, D. L., Currier, J. R., Seder, R.. 2021-12-27. mRNA-1273 vaccination protects against SARS-CoV-2 elicited lung inflammation in non-human primates. https://doi.org/10.1101/2021.12.24.474132

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