Invited Speaker CD1-MR1 Workshop 2025

Optimisation of NKT cell-mediated adjuvant activity for mRNA vaccines (#12)

Gavin Painter 1
  1. Victoria University of Wellington, Lower Hutt, New Zealand

In C57BL/6 mice, we reported1 that the co-encapsulation of NKT cell agonist compounds substituted at the galactosyl 6 hydroxyl position together with enzymatically capped and tailed mRNA in liposomal formulations can function as a highly effective vaccine for malaria through the production of pathogen-specific liver tissue resident memory T cells (Trm). In this paper we will present our NKT cell ligand SAR data in transgenic mice expressing human CD1d and NKT TCR molecules2 in an updated vaccine format utilizing industry standard mRNA lipid nanoparticles.

  1. Ganley, M.; Holz, L. E.; Minnell, J. J.; de Menezes, M. N.; Burn, O. K.; Poa, K. C. Y.; Draper, S. L.; English, K.; Chan, S. T. S.; Anderson, R. J.; Compton, B. J.; Marshall, A. J.; Cozijnsen, A.; Chua, Y. C.; Ge, Z.; Farrand, K. J.; Mamum, J. C.; Xu, C.; Cockburn, I. A.; Yui, K.; Bertolino, P.; Gras, S.; Le Nours, J.; Rossjohn, J.; Fernandez-Ruiz, D.; McFadden, G. I.; Ackerley, D. F.; Painter, G. F.; Hermans, I. F.; Heath, W. R., mRNA vaccine against malaria tailored for liver-resident memory T cells. Nat. Immunol. 2023, 24 (9), 1487-1498.
  2. Saavedra-Avila, N. A.; Dellabona, P.; Casorati, G.; Veerapen, N.; Besra, G. S.; Howell, A. R.; Porcelli, S. A., A humanized mouse model for in vivo evaluation of invariant Natural Killer T cell responses. Front Immunol 2022, 13, 1011209.