Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Advax adjuvant formulations promote protective immunity against aerosol Mycobacterium tuberculosis in the absence of deleterious inflammation and reactogenicity

View ORCID ProfileDiana H. Quan, Claudio Counoupas, Gayathri Nagalingam, Rachel Pinto, Nikolai Petrovsky, Warwick J. Britton, James A. Triccas
doi: https://doi.org/10.1101/2020.10.01.323105
Diana H. Quan
1Discipline of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006, NSW, Australia
2Tuberculosis Research Program, Centenary Institute, The University of Sydney, 2006, NSW, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Diana H. Quan
Claudio Counoupas
1Discipline of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006, NSW, Australia
2Tuberculosis Research Program, Centenary Institute, The University of Sydney, 2006, NSW, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gayathri Nagalingam
1Discipline of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006, NSW, Australia
2Tuberculosis Research Program, Centenary Institute, The University of Sydney, 2006, NSW, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rachel Pinto
1Discipline of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006, NSW, Australia
2Tuberculosis Research Program, Centenary Institute, The University of Sydney, 2006, NSW, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nikolai Petrovsky
3Department of Endocrinology, Flinders University, Adelaide, Australia and Vaxine Pty Ltd, Adelaide 5042, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Warwick J. Britton
1Discipline of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006, NSW, Australia
2Tuberculosis Research Program, Centenary Institute, The University of Sydney, 2006, NSW, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James A. Triccas
1Discipline of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006, NSW, Australia
2Tuberculosis Research Program, Centenary Institute, The University of Sydney, 2006, NSW, Australia
4Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, 2050, NSW, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jamie.triccas@sydney.edu.au
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The development of safe and effective adjuvants is a critical goal of vaccine development programs. In this report, we defined the immunostimulatory profile and protective effect against aerosol Mycobacterium tuberculosis infection of vaccine formulations incorporating the semi-crystalline adjuvant δ-inulin (Advax). Advax formulated with CpG oligonucleotide and the QS-21 saponin (AdvaxCpQS) was the most effective combination, demonstrated by the capacity of CysVac2/AdvaxCpQS to significantly reduce the bacterial burden in the lungs of M. tuberculosis-infected mice. CysVac2/AdvaxCpQS protection was associated with rapid influx of neutrophils, macrophages and monocytes to the site of vaccination and the induction of antigen-specific IFN-γ+/IL-2+/TNF+ polyfunctional CD4+ T cells in the lung. When compared to the highly potent adjuvant combination of monophosphoryl lipid A and dimethyldioctadecylammonium bromide (MPL/DDA), AdvaxCpQS imparted a similar level of protective efficacy yet without the profound stimulation of inflammatory cytokines and vaccination site ulceration observed with MPL/DDA. Addition of DDA to CysVac2/ AdvaxCpQS further improved the protective effect of the vaccine, which correlated with increased polyfunctional CD4+ T cells in the lung but with no increase in vaccine reactogenicity. The data demonstrate that Advax formulations can decouple protective tuberculosis immunity from reactogenicity, making them ideal candidates for human application.

Highlights

  • Advax adjuvant formulations improve pulmonary protection against aerosol Mycobacterium tuberculosis infection

  • Different combinations of adjuvant components markedly influence the level of protection observed

  • Protection is associated with the rapid influx of myeloid cells to the site of vaccination and the induction of antigen-specific polyfunctional CD4+ T cells in the lung.

  • Advax formulations abrogate vaccine-site ulceration and inflammatory cytokine production

Competing Interest Statement

N.P. is an inventor on patents over Advax and has interests in Vaxine Pty Ltd, which owns interests in the Advax patents. W.B. and J.T. are inventors on patents over CysVac2. The authors declare that they have no known competing financial interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted October 01, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Advax adjuvant formulations promote protective immunity against aerosol Mycobacterium tuberculosis in the absence of deleterious inflammation and reactogenicity
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Advax adjuvant formulations promote protective immunity against aerosol Mycobacterium tuberculosis in the absence of deleterious inflammation and reactogenicity
Diana H. Quan, Claudio Counoupas, Gayathri Nagalingam, Rachel Pinto, Nikolai Petrovsky, Warwick J. Britton, James A. Triccas
bioRxiv 2020.10.01.323105; doi: https://doi.org/10.1101/2020.10.01.323105
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Advax adjuvant formulations promote protective immunity against aerosol Mycobacterium tuberculosis in the absence of deleterious inflammation and reactogenicity
Diana H. Quan, Claudio Counoupas, Gayathri Nagalingam, Rachel Pinto, Nikolai Petrovsky, Warwick J. Britton, James A. Triccas
bioRxiv 2020.10.01.323105; doi: https://doi.org/10.1101/2020.10.01.323105

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (2646)
  • Biochemistry (5270)
  • Bioengineering (3682)
  • Bioinformatics (15798)
  • Biophysics (7259)
  • Cancer Biology (5629)
  • Cell Biology (8102)
  • Clinical Trials (138)
  • Developmental Biology (4769)
  • Ecology (7522)
  • Epidemiology (2059)
  • Evolutionary Biology (10585)
  • Genetics (7733)
  • Genomics (10137)
  • Immunology (5197)
  • Microbiology (13918)
  • Molecular Biology (5390)
  • Neuroscience (30799)
  • Paleontology (215)
  • Pathology (879)
  • Pharmacology and Toxicology (1525)
  • Physiology (2255)
  • Plant Biology (5025)
  • Scientific Communication and Education (1042)
  • Synthetic Biology (1388)
  • Systems Biology (4149)
  • Zoology (812)