Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Aid, Malika, Vidal, Samuel J., Piedra-Mora, Cesar, Ducat, Sarah, Chan, Chi N., Bondoc, Stephen, Colarusso, Alessandro, Starke, Carly E., Nekorchuk, Michael, Busman-Sahay, Kathleen, Estes, Jacob D., Martinot, Amanda J., Barouch, Dan H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020736/
https://www.ncbi.nlm.nih.gov/pubmed/35395058
http://dx.doi.org/10.1371/journal.ppat.1009990
_version_ 1784689623887249408
author Aid, Malika
Vidal, Samuel J.
Piedra-Mora, Cesar
Ducat, Sarah
Chan, Chi N.
Bondoc, Stephen
Colarusso, Alessandro
Starke, Carly E.
Nekorchuk, Michael
Busman-Sahay, Kathleen
Estes, Jacob D.
Martinot, Amanda J.
Barouch, Dan H.
author_facet Aid, Malika
Vidal, Samuel J.
Piedra-Mora, Cesar
Ducat, Sarah
Chan, Chi N.
Bondoc, Stephen
Colarusso, Alessandro
Starke, Carly E.
Nekorchuk, Michael
Busman-Sahay, Kathleen
Estes, Jacob D.
Martinot, Amanda J.
Barouch, Dan H.
author_sort Aid, Malika
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9020736
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-90207362022-04-21 Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques Aid, Malika Vidal, Samuel J. Piedra-Mora, Cesar Ducat, Sarah Chan, Chi N. Bondoc, Stephen Colarusso, Alessandro Starke, Carly E. Nekorchuk, Michael Busman-Sahay, Kathleen Estes, Jacob D. Martinot, Amanda J. Barouch, Dan H. PLoS Pathog Research Article 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. Public Library of Science 2022-04-08 /pmc/articles/PMC9020736/ /pubmed/35395058 http://dx.doi.org/10.1371/journal.ppat.1009990 Text en © 2022 Aid et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Aid, Malika
Vidal, Samuel J.
Piedra-Mora, Cesar
Ducat, Sarah
Chan, Chi N.
Bondoc, Stephen
Colarusso, Alessandro
Starke, Carly E.
Nekorchuk, Michael
Busman-Sahay, Kathleen
Estes, Jacob D.
Martinot, Amanda J.
Barouch, Dan H.
Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques
title Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques
title_full Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques
title_fullStr Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques
title_full_unstemmed Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques
title_short Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques
title_sort ad26.cov2.s prevents upregulation of sars-cov-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020736/
https://www.ncbi.nlm.nih.gov/pubmed/35395058
http://dx.doi.org/10.1371/journal.ppat.1009990
work_keys_str_mv AT aidmalika ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT vidalsamuelj ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT piedramoracesar ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT ducatsarah ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT chanchin ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT bondocstephen ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT colarussoalessandro ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT starkecarlye ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT nekorchukmichael ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT busmansahaykathleen ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT estesjacobd ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT martinotamandaj ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques
AT barouchdanh ad26cov2spreventsupregulationofsarscov2inducedpathwaysofinflammationandthrombosisinhamstersandrhesusmacaques