ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Differential gene expression profiles of lung-resident memory CD4+ T cells induced by different pulmonary vaccines against Mycobacterium tuberculosis (#266)

Ellis Armitage 1 , Erica Stewart 2 3 , Diana Quan 1 , Claudio Counoupas 1 3 , Manuela Florido 1 , Nikolai Petrovsky 4 5 , James Triccas 2 3 , Warwick Britton 1 6
  1. Centenary Institute, University of Sydney, Tuberculosis Research Program, Sydney, NSW, Australia
  2. University of Sydney, Charles Perkins Centre and Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney, NSW, Australia
  3. Charles Perkins Centre, University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, NSW, Australia
  4. Vaxine Pty Ltd, Adelaide, SA, Australia
  5. Flinders University, College of Medicine and Public Health, Adelaide, SA, Australia
  6. Royal Prince Alfred Hospital, Department of Clinical Immunology, Sydney, NSW, Australia

Mycobacterium tuberculosis is a major human pathogen and the existing tuberculosis (TB) vaccine, BCG, is ineffective at preventing its transmission. Understanding the immunological characteristics of protective immunity is essential for the rational design of improved TB vaccines. We have shown pulmonary immunisation with two novel vaccines, the recombinant influenza A virus (rIAV) PR8.p25 and the M. tuberculosis fusion protein-adjuvant vaccine, CysVac2-Advax, is protective against M. tuberculosis in mice. This protective immunity is associated with the development of M. tuberculosis antigen-specific CD4+ resident memory T cells (TRM­) in the lungs, which protect against TB by rapidly responding to pathogen exposure. Genes involved in the formation and effector functions of CD4+ TRM are poorly understood. To characterise differences in gene expression of pulmonary vaccine-induced TRM, we adoptively transferred into C57BL/6 mice TCR-transgenic CD4+ T cells specific for IAb-restricted p25 peptide, present in both vaccines, and immunised them with either vaccine by the pulmonary route. After six weeks, we isolated p25-specific CD4+ TRM from the lungs by FACS sorting, and measured their gene expression profiles with the Nanostring™ immunology panel supplemented by genes associated with TRM. TRM induced by rIAV showed differential expression of 238 genes compared with naïve T cells, of which 43 were also differentially regulated compared to effector and effector memory T cells. Principal component analysis showed that they differed from these T cell populations in their upregulation of many genes, including chemokine receptors, transcription factors and effector molecules. TRM induced by CysVac2-Advax shared an overlapping gene expression profile to rIAV-induced TRM, with both groups upregulating chemokine receptors and effector genes. CysVac2-Advax TRM uniquely elevated expression of genes related to Th17 differentiation, while rIAV TRM upregulated other transcription factors and effector genes. Therefore, TRM induced by both vaccines protect against M. tuberculosis, but through distinct effector mechanisms.

  1. Flórido M, et al.. Pulmonary immunization with a recombinant Influenza A virus vaccine induces lung-resident CD4+ memory T cells that are associated with protection against tuberculosis. Mucosal Immunology 2018; 11:1743–1752.
  2. Counoupas C, et al. (2020) Mucosal delivery of a multistage subunit vaccine promotes development of lung-resident memory T cells and affords interleukin-17-dependant protection against pulmonary tuberculosis. NPJ Vaccines 2020; 5:105.