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| Status |
Public on Dec 01, 2021 |
| Title |
mRNA vaccine efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after the challenge |
| Organism |
Mesocricetus auratus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
mRNA-1273, an mRNA-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is efficacious in mouse and non-human primate models of mild COVID-19. Hamsters exhibit more severe clinical disease from SARS-CoV-2, making it an important model to evaluate vaccine efficacy. Here we show that mock-vaccine treated hamsters infected with SARS-CoV-2 show weight loss and pulmonary infection with pathological changes and increased activated interstitial macrophages and other immune cell types. Prime-boost administration of mRNA-1273 elicited dose-independent robust binding and neutralizing antibodies, ameliorated weight loss and suppressed virus replication in the upper and lower airways. Vaccination largely prevented pulmonary pathological changes, antiviral immune cell activation and changes in cell type composition although increases in some immune cell types and activation of regulatory pathways were found and coincided with an anamnestic antibody response. The results characterize unexpected pulmonary cellular responses to SARS-CoV-2 in vaccinated animals that were shared but greatly attenuated, when compared to mock-vaccinated animals. The efficacy of mRNA-1273 is demonstrated as a two-dose vaccination schedule in a model of severe COVID-19.
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| Overall design |
Single cell RNA sequencing was conducted on fourteen samples of the Syrian golden hamster lung tissue. Samples were from naïve, mock-vaccinated + SARS-CoV-2 infected, and mRNA-1273 vaccinated + SARS-CoV-2 infected hamsters.
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| Contributor(s) |
Meyer M, Wang Y, Edwards D, Smith GR, Rubenstein AB, Ramanathan P, Mire CE, Pietzsch C, Chen X, Ge Y, Cheng WS, Henry C, Woods A, Ma LZ, Stewart-Jones G, Bock KW, Minai M, Nagata BM, Periasamy S, Shi PY, Graham BS, Moore IN, Ramos I, Troyanskaya OG, Zaslavsky E, Carfi A, Sealfon SC, Bukreyev A |
| Citation(s) |
34449440 |
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| Submission date |
Dec 24, 2020 |
| Last update date |
Dec 03, 2021 |
| Contact name |
Aliza Rubenstein |
| E-mail(s) |
aliza.rubenstein@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Street address |
1 Gustave L. Levy Pl
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| City |
Manhattan |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL28997 |
Illumina NovaSeq 6000 (Mesocricetus auratus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA687740 |
| SRA |
SRP299282 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE163838_RAW.tar |
621.3 Mb |
(http)(custom) |
TAR (of H5, TAR) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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