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

Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J. Britton, Nikolai Petrovsky, James A. Triccas

    Research output: Contribution to journalArticlepeer-review

    25 Citations (Scopus)
    17 Downloads (Pure)

    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 (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.

    Original languageEnglish
    Article number8582
    Number of pages11
    JournalScientific Reports
    Volume7
    DOIs
    Publication statusPublished - 2017

    Bibliographical note

    This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made.

    Keywords

    • Mycobacterium tuberculosis
    • vaccine
    • Advax
    • immunity

    Fingerprint

    Dive into the research topics of 'Delta inulin-based adjuvants promote the generation of polyfunctional CD4 <sup>+</sup> T cell responses and protection against Mycobacterium tuberculosis infection'. Together they form a unique fingerprint.

    Cite this