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mRNA-1273 vaccination protects against SARS-CoV-2–elicited lung inflammation in nonhuman primates
Adam T. Waickman, … , Jeffrey R. Currier, Robert Seder
Adam T. Waickman, … , Jeffrey R. Currier, Robert Seder
Published June 2, 2022
Citation Information: JCI Insight. 2022;7(13):e160039. https://doi.org/10.1172/jci.insight.160039.
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Research Article COVID-19 Immunology

mRNA-1273 vaccination protects against SARS-CoV-2–elicited lung inflammation in nonhuman primates

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Abstract

Vaccine-elicited SARS-CoV-2 antibody responses are an established correlate of protection against viral infection in humans and nonhuman 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 after 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 after 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 and CCL3, and the broad expression of IFN-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 prechallenge 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.

Authors

Adam T. Waickman, Kaitlin Victor, Krista Newell, Tao Li, Heather Friberg, Kathryn E. Foulds, Mario Roederer, Diane L. Bolton, Jeffrey R. Currier, Robert Seder

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Figure 1

Identification and quantification of BALF cells by scRNA-Seq.

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Identification and quantification of BALF cells by scRNA-Seq.
(A) UMAP p...
(A) UMAP projection of BALF cells captured by scRNA-Seq analysis. (B) Expression of key linage-specific genes in all annotated cell types. (C) Frequency of epithelial cell populations. (D) Frequency of lymphocyte cell populations. (E) Frequency of dendritic cell populations. (F) Frequency of macrophage populations. *P < 0.05, paired t test.

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