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

Characterisation of a glycolipid-peptide vaccine for prevention of malaria (#248)

Yu Cheng Chua 1 , Lauren Holz 1 2 , Sarah Draper 3 , Anton Cozijnsen 4 , Geoffrey McFadden 4 , Ian Hermans 5 6 7 , Gavin Painter 3 6 , William Heath 1 2
  1. Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia
  2. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia
  3. Ferrier Research Institute, Victoria University of Wellington, Lower Hutt, New Zealand
  4. School of BioSciences, University of Melbourne, Parkville, Australia
  5. Malaghan Institute of Medical Research, Wellington, New Zealand
  6. Avalia Immunotherapies Limited, Lower Hutt, New Zealand
  7. Maurice Wilkins Centre for Molecular Biodiscovery, Wellington, New Zealand

Malaria is caused by Plasmodium parasites and is a major public health issue in many countries, particularly in Africa. It is well established in mice that tissue-resident memory (Trm) CD8+ cells are crucial for protection against liver stage malaria. However, there is no simple vaccine formulation that can effectively generate these cells. Here, we report the development of a synthetic glycolipid-peptide vaccine that is highly effective at inducing liver Trm cells. This vaccine was dependent on priming by XCR1+ type 1 conventional dendritic cells (cDC1s). After initial T cell activation, we showed that antigen and inflammation provided by the conjugate vaccine can further influence the seeding and longevity of liver Trm cells. Our longitudinal analysis revealed that a single vaccination induced large numbers of endogenous malaria-specific Trm cells that persisted for more than 300 days in the liver and conferred substantial protection against sporozoite challenge. The vaccine response can be improved by homologous prime-boost immunization, ideally with a 60-day delay between injections. Lastly, vaccination against Kb90, an MHC-I restricted epitope identified from the peptide library screening, can induce liver Trm generation and confer high levels of sterile protection against malaria, demonstrating the identification of a novel protective malaria epitope. Overall, our results highlight the effectiveness of conjugate vaccines at generating liver Trm-mediated immunity against malaria.