RESEARCH ARTICLE Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques

Malika Aid, Samuel J. Vidal, Cesar Piedra-Mora, Sarah Ducat, Chi N. Chan, Stephen Bondoc, Alessandro Colarusso, Carly E. Starke, Michael Nekorchuk, Kathleen Busman-Sahay, Jacob D. Estes, Amanda J. Martinot, Dan H. Barouch

Research output: Contribution to journalArticlepeer-review

Abstract

Syrian golden hamsters exhibit features of severe disease after SARS-CoV-2 WA1/2020 challenge and are therefore useful models of COVID-19 pathogenesis and prevention with vaccines. Recent studies have shown that SARS-CoV-2 infection stimulates type I interferon, myeloid, and inflammatory signatures similar to human disease and that weight loss can be prevented with vaccines. However, the impact of vaccination on transcriptional programs associated with COVID-19 pathogenesis and protective adaptive immune responses is unknown. Here we show that SARS-CoV-2 WA1/2020 challenge in hamsters stimulates myeloid and inflammatory programs as well as signatures of complement and thrombosis associated with human COVID-19. Notably, immunization with Ad26.COV2.S, an adenovirus serotype 26 vector (Ad26)-based vaccine expressing a stabilized SARS-CoV-2 spike protein, prevents the upregulation of these pathways, such that the mRNA expression profiles of vaccinated hamsters are comparable to uninfected animals. Using proteomics profiling, we validated these findings in rhesus macaques challenged with SARS-CoV-2 WA1/ 2020 or SARS-CoV-2 B.1.351. Finally, we show that Ad26.COV2.S vaccination induces T and B cell signatures that correlate with binding and neutralizing antibody responses weeks following vaccination. These data provide insights into the molecular mechanisms of Ad26. COV2.S protection against severe COVID-19 in animal models.

Original languageEnglish (US)
Article numbere1009990
JournalPLoS pathogens
Volume18
Issue number4
DOIs
StatePublished - Apr 2022

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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