Dataset Information

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 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-?⁺TNF⁺IL-2⁺). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (Advax^CpG), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/Advax^CpG 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/Advax^CpG is a strong candidate for further preclinical evaluation for progression to human trials.

SUBMITTER: Counoupas C

PROVIDER: S-EPMC5561132 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Counoupas Claudio C Pinto Rachel R Nagalingam Gayathri G Britton Warwick J WJ Petrovsky Nikolai N Triccas James A JA

Scientific reports 20170817 1

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 infectio ...[more]

PMID: 28819247

Similar Datasets

Project description:BackgroundRapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue.MethodsParticipants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4+ T cells defined by IFN-γ, TNF-α, and IL-2 expression upon MTB antigen stimulation.ResultsA total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-γ, TNF-α, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-α+ or IL-2+ cells had superiority over that on IFN-γ+ cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-α+IL-2+ cells produced an AUC of 0.901 (95% CI, 0.833-0.969), with a sensitivity of 93.75% (95% CI, 79.85-98.27%) and specificity of 72.97% (95% CI, 57.02-84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-α+IL-2+ cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19-97.47%) sensitivity and 68.97% (95% CI, 50.77-82.73%) specificity.ConclusionsWe demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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