MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies

Abstract A single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a signif...

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Autores principales:	Andrew D. White, Laura Sibley, Charlotte Sarfas, Alexandra Morrison, Jennie Gullick, Simon Clark, Fergus Gleeson, Anthony McIntyre, Cecilia Lindestam Arlehamn, Alessandro Sette, Francisco J. Salguero, Emma Rayner, Esteban Rodriguez, Eugenia Puentes, Dominick Laddy, Ann Williams, Mike Dennis, Carlos Martin, Sally Sharpe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/75a0f9423daa48f5b1801560e5f933f6
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spelling	oai:doaj.org-article:75a0f9423daa48f5b1801560e5f933f62021-12-02T15:08:21ZMTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies10.1038/s41541-020-00262-82059-0105https://doaj.org/article/75a0f9423daa48f5b1801560e5f933f62021-01-01T00:00:00Zhttps://doi.org/10.1038/s41541-020-00262-8https://doaj.org/toc/2059-0105Abstract A single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-γ+TNF-α+IL2+) and multi-(IFN-γ+TNF-α+) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-γ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns.Andrew D. WhiteLaura SibleyCharlotte SarfasAlexandra MorrisonJennie GullickSimon ClarkFergus GleesonAnthony McIntyreCecilia Lindestam ArlehamnAlessandro SetteFrancisco J. SalgueroEmma RaynerEsteban RodriguezEugenia PuentesDominick LaddyAnn WilliamsMike DennisCarlos MartinSally SharpeNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Andrew D. White Laura Sibley Charlotte Sarfas Alexandra Morrison Jennie Gullick Simon Clark Fergus Gleeson Anthony McIntyre Cecilia Lindestam Arlehamn Alessandro Sette Francisco J. Salguero Emma Rayner Esteban Rodriguez Eugenia Puentes Dominick Laddy Ann Williams Mike Dennis Carlos Martin Sally Sharpe MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies
description	Abstract A single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-γ+TNF-α+IL2+) and multi-(IFN-γ+TNF-α+) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-γ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns.
format	article
author	Andrew D. White Laura Sibley Charlotte Sarfas Alexandra Morrison Jennie Gullick Simon Clark Fergus Gleeson Anthony McIntyre Cecilia Lindestam Arlehamn Alessandro Sette Francisco J. Salguero Emma Rayner Esteban Rodriguez Eugenia Puentes Dominick Laddy Ann Williams Mike Dennis Carlos Martin Sally Sharpe
author_facet	Andrew D. White Laura Sibley Charlotte Sarfas Alexandra Morrison Jennie Gullick Simon Clark Fergus Gleeson Anthony McIntyre Cecilia Lindestam Arlehamn Alessandro Sette Francisco J. Salguero Emma Rayner Esteban Rodriguez Eugenia Puentes Dominick Laddy Ann Williams Mike Dennis Carlos Martin Sally Sharpe
author_sort	Andrew D. White
title	MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies
title_short	MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies
title_full	MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies
title_fullStr	MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies
title_full_unstemmed	MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies
title_sort	mtbvac vaccination protects rhesus macaques against aerosol challenge with m. tuberculosis and induces immune signatures analogous to those observed in clinical studies
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/75a0f9423daa48f5b1801560e5f933f6
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MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies

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