Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection

Abstract There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and ha...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J. Britton, Nikolai Petrovsky, James A. Triccas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/00c5fecbb81548f3b3341ecbfce75e2a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:00c5fecbb81548f3b3341ecbfce75e2a
record_format	dspace
spelling	oai:doaj.org-article:00c5fecbb81548f3b3341ecbfce75e2a2021-12-02T12:30:36ZDelta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection10.1038/s41598-017-09119-y2045-2322https://doaj.org/article/00c5fecbb81548f3b3341ecbfce75e2a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09119-yhttps://doaj.org/toc/2045-2322Abstract There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis-infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4+ T cells (IFN-γ+TNF+IL-2+). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (AdvaxCpG), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/AdvaxCpG resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2-specific CD4+ T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/AdvaxCpG is a strong candidate for further preclinical evaluation for progression to human trials.Claudio CounoupasRachel PintoGayathri NagalingamWarwick J. BrittonNikolai PetrovskyJames A. TriccasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudio Counoupas Rachel Pinto Gayathri Nagalingam Warwick J. Britton Nikolai Petrovsky James A. Triccas Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection
description	Abstract There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis-infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4+ T cells (IFN-γ+TNF+IL-2+). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (AdvaxCpG), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/AdvaxCpG resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2-specific CD4+ T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/AdvaxCpG is a strong candidate for further preclinical evaluation for progression to human trials.
format	article
author	Claudio Counoupas Rachel Pinto Gayathri Nagalingam Warwick J. Britton Nikolai Petrovsky James A. Triccas
author_facet	Claudio Counoupas Rachel Pinto Gayathri Nagalingam Warwick J. Britton Nikolai Petrovsky James A. Triccas
author_sort	Claudio Counoupas
title	Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection
title_short	Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection
title_full	Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection
title_fullStr	Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection
title_full_unstemmed	Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection
title_sort	delta inulin-based adjuvants promote the generation of polyfunctional cd4+ t cell responses and protection against mycobacterium tuberculosis infection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/00c5fecbb81548f3b3341ecbfce75e2a
work_keys_str_mv	AT claudiocounoupas deltainulinbasedadjuvantspromotethegenerationofpolyfunctionalcd4tcellresponsesandprotectionagainstmycobacteriumtuberculosisinfection AT rachelpinto deltainulinbasedadjuvantspromotethegenerationofpolyfunctionalcd4tcellresponsesandprotectionagainstmycobacteriumtuberculosisinfection AT gayathrinagalingam deltainulinbasedadjuvantspromotethegenerationofpolyfunctionalcd4tcellresponsesandprotectionagainstmycobacteriumtuberculosisinfection AT warwickjbritton deltainulinbasedadjuvantspromotethegenerationofpolyfunctionalcd4tcellresponsesandprotectionagainstmycobacteriumtuberculosisinfection AT nikolaipetrovsky deltainulinbasedadjuvantspromotethegenerationofpolyfunctionalcd4tcellresponsesandprotectionagainstmycobacteriumtuberculosisinfection AT jamesatriccas deltainulinbasedadjuvantspromotethegenerationofpolyfunctionalcd4tcellresponsesandprotectionagainstmycobacteriumtuberculosisinfection
_version_	1718394315995086848

Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection

Ejemplares similares