Poster Presentation The Melbourne Immunotherapy Network Winter Symposium 2019

Towards a universal Mucosal-Associated Invariant T (MAIT) CELL-based vaccination for better protection against microbial infections (#115)

Huimeng Wang 1 , Lars Kjer-Nielsen 1 , James McCluskey 1 , Richard Strugnell 1 , Alexandra Corbett 1 , Zhenjun Chen 1
  1. Peter Doherty Institute,University of Melbourne, Melbourne, VIC, Australia

Mucosal-associated Invariant T (MAIT) cells recognise a unique set antigens including 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), bound to MHC Class I-related protein-1 (MR1). These antigens are derived from the riboflavin synthesis pathway present in most microbes, and absent from mammals, rendering them as a signature of microbial infection. Features of tissue resident memory and preferential localisation at the host—pathogen interface enable MAIT cells quick response at the front line against microbial infections.

The highly conserved MR1-MAIT axis, monomorphic nature of MR1 and the conserved essential microbial riboflavin biosynthetic pathway, makes MAIT cells an ideal therapeutic target. Potential MAIT cell-based interventions or vaccination strategies targeting MAIT cells will be applicable to all human individuals (NOT restricted by MHC polymorphism) and may also to other mammalian species (pigs, cattle and sheep).

We have shown that MAIT cells are capable of forming long-term memory, which provides the foundation for vaccination. Substantial studies elucidated the requirements for MAIT cell activation in vivo, which now allow us to efficiently manipulate MAIT immunity, and optimise the vaccination components for better protection against microbial infections, in particular those pathogens with multiple drug resistance.

  1. Wang H, .....Kjer-Nielsen L, Strugnell RA, McCluskey J, Corbett AJ, Hinks TSC*, Chen Z*. MAIT cells protect against pulmonary Legionella longbeachae infection. Nat Commun. 2018 Aug 22;9(1):3350.
  2. Z Chen* , H Wang*, ...J McCluskey and A J Corbett . Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals. Mucosal Immunology, 2017; 10, 58-68