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

doi:10.1016/j.vaccine.2021.02.041

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

Vaccine. 2021 Apr 1;39(14):1990-1996. doi: 10.1016/j.vaccine.2021.02.041. Epub 2021 Mar 11.

Authors

Diana H Quan¹, Claudio Counoupas¹, Gayathri Nagalingam¹, Rachel Pinto¹, Nikolai Petrovsky², Warwick J Britton³, James A Triccas⁴

Affiliations

¹ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006 NSW, Australia; Tuberculosis Research Program, Centenary Institute, The University of Sydney, 2006 NSW, Australia.
² Department of Endocrinology, Flinders University, Adelaide, Australia; Vaxine Pty Ltd, Adelaide 5042, Australia.
³ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006 NSW, Australia; Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, 2050 NSW, Australia.
⁴ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, 2006 NSW, Australia; Tuberculosis Research Program, Centenary Institute, The University of Sydney, 2006 NSW, Australia; Charles Perkins Centre and Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, 2006 NSW, Australia. Electronic address: jamie.triccas@sydney.edu.au.

PMID: 33714652
DOI: 10.1016/j.vaccine.2021.02.041

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 (Advax^CpQS) was the most effective combination, demonstrated by the capacity of CysVac2/Advax^CpQS to significantly reduce the bacterial burden in the lungs of M. tuberculosis-infected mice. CysVac2/Advax^CpQS 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), Advax^CpQS 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/Advax^CpQS 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.

Keywords: Adjuvant; Advax; Protective vaccine; Reactogenicity; Tuberculosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Aerosols
Animals
Inflammation
Inulin / analogs & derivatives
Mice
Mice, Inbred C57BL
Mycobacterium tuberculosis*
Tuberculosis Vaccines*

Substances

Adjuvants, Immunologic
Aerosols
Tuberculosis Vaccines
delta inulin
Inulin

Grants and funding

U01 AI061142/AI/NIAID NIH HHS/United States