Poster Presentation 8th Australasian Vaccines & Immunotherapeutics Development Meeting 2020

Optimising novel adjuvant formulations to promote protective immunity without reactogenicity (#208)

Diana H Quan 1 , Claudio Counoupas 1 , Gayathri Nagalingam 2 , Rachel Pinto 2 , Nikolai Petrovsky 3 , Warwick J Britton 1 , Jamie Triccas 2
  1. Tuberculosis Research Program, Centenary Institute, Camperdown, NSW, Australia
  2. The University of Sydney, Camperdown
  3. Flinders University, Adelaide

Tuberculosis (TB) is the leading cause of disease from a single infectious agent, causing an estimated 1.5 million deaths and infecting an estimated 10 million individuals in 2018 (1). The current vaccine, Mycobacterium bovis Bacillus Calmette–Guérin (BCG), is particularly effective at reducing the incidence of childhood TB, miliary TB and meningitis (2) but overall BCG efficacy in the lungs varies greatly depending on age of administration, localisation of TB infection, geographical area where vaccine is administered, previous exposure to various mycobacteria and current immune status (3). To improve protective efficacy, subunit vaccine strategies are highly attractive avenues of inquiry, and thus the development of safe and effective adjuvants is a critical goal of TB vaccine development programs. In this study, we defined the immunostimulatory profile and protective effect against aerosol Mycobacterium tuberculosis infection of vaccine formulations incorporating the semi-crystalline adjuvant d-inulin (Advax) (4, 5). 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.

  1. WHO. Global Tuberculosis Report 2019. Geneva: World Health Organisation; 2019.
  2. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994;271(9):698-702.
  3. Mangtani P, Abubakar I, Ariti C, Beynon R, Pimpin L, Fine PE, et al. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis. 2014;58(4):470-80.
  4. Counoupas C, Pinto R, Nagalingam G, Hill-Cawthorne GA, Feng CG, Britton WJ, et al. Mycobacterium tuberculosis components expressed during chronic infection of the lung contribute to long-term control of pulmonary tuberculosis in mice. Npj Vaccines. 2016;1.
  5. Counoupas C, Pinto R, Nagalingam G, Britton WJ, Petrovsky N, Triccas JA. Delta inulin-based adjuvants promote the generation of polyfunctional CD4(+) T cell responses and protection against Mycobacterium tuberculosis infection. Sci Rep. 2017;7(1):8582.