Cytotoxic T cell responses against liver-stage malaria: Implications for T cell-based vaccine development

Abstract

The Plasmodium parasite annually causes 200 million human malaria infections and 655.000 deaths. Prophylactic drugs are available, but resistance against these is developing in the field. A vaccine against this disease is therefore highly desired. The only vaccine candidate tested in phase III clinical trials is RTS,S, but the efficacy rates of this vaccine are disappointing. RTS,S elicits mainly humoral immunity, yet human and murine studies suggest that T cell immunity plays an important role in protective immunity against malaria. Because the Plasmodium parasite only resides in MHC-expressing cells during the liver stage, this stage is being investigated as a target for new vaccines. Only a limited number of antigens is known to date, and also the mechanism of action through which human T cells respond remains unclear. If these cells, not only CD8+ but also CD4+ T lymphocytes, exert cytotoxic functions, a variety of assays is available to test and quantify antigen-specific killing of target cells. New insights in liver-stage antigens, the mechanism through which infected cells are cleared and whether T cells confer protective immune responses in man, are required for the development of a T cell-based vaccine against malaria.