Poster Presentation First Malaria World Congress 2018

Development of Plasmodium-specific liver resident-memory CD8+ T cells after Heat-Killed Immunization (#289)

Sonia Ghilas 1 , Fernandez-Ruiz Daniel 1 , Holz Lauren 1 , Cozijnsen Anton 2 , Mollard Vanessa 2 , Geoff Mcfadden 2 , William Heath 1
  1. Peter Doherty Institute, Melbourne, VICTORIA, Australia
  2. School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia

It is of major interest to develop an efficient vaccine to prevent emergence of Malaria disease. Most of the vaccination strategies that have been develop focus on the asymptomatic pre-erythrocytic stages of the infection and aim to control the infection before Plasmodium parasites spread into the blood and trigger malaria symptoms. One way to control infection is to induce the development of memory T cells. The use of living sporozoites attenuated by radiation (RAS) has been shown to confer a sterile immunity by enhancing the development of specific memory CD8+T cells. We have previously described a T cell receptor (TCR) transgenic mouse, named PbT-I, in which all TCR expressed by CD8+T cells specifically recognize a Plasmodium antigen. Using these TCR transgenic mice and RAS vaccination, we have shown that resident-memory T cells (Trm cells) develop in the liver and are essential for protection against pre-erytrocytic stages of Plasmodium development. Here we examined whether non-living sporozoites could trigger the development of Plasmodium-specific memory CD8+T cells and, specifically, liver-Trm.We used heat-killed sporozoites to immunize mice transferred with PbT-I cells and then assessed the differentiation of PbT-I cells into memory cells. We found that after vaccination with heat-killed sporozoites, memory PbT-I cells developed in the spleen, liver and lymph nodes, but the number of these cells was significantly reduced relative to RAS immunised mice. Importantly, we were able to detect liver-Trm generation by heat-killed immunization, but again, the number of Plasmodium-specific liver-Trm recovered after heat-killed sporozoite immunization was less than one tenth that induced by RAS. Our goal now is to investigate whether we can improve the development of Plasmodium-specific liver-Trm after heat-killed immunization by combining this form of antigen with different adjuvants. This could lead to development of a vaccination strategy that does not require live sporozoites,providing greater utility.