title: Induction and maintenance of protective CD8+ T cells against malaria liver stages: implications for vaccine development.
abstract: CD8+ T cells against malaria liver stages represent a major protective immune mechanism against infection. Following induction in the peripheral lymph nodes by dendritic cells (DCs), these CD8+ T cells migrate to the liver and eliminate parasite infected hepatocytes. The processing and presentation of sporozoite antigen requires TAP mediated transport of major histocompatibility complex class I epitopes to the endoplasmic reticulum. Importantly, in DCs this process is also dependent on endosome-mediated cross presentation while this mechanism is not required for epitope presentation on hepatocytes. Protective CD8+ T cell responses are strongly dependent on the presence of CD4+ T cells and the capacity of sporozoite antigen to persist for a prolonged period of time. While human trials with subunit vaccines capable of inducing antibodies and CD4+ T cell responses have yielded encouraging results, an effective anti-malaria vaccine will likely require vaccine constructs designed to induce protective CD8+ T cells against malaria liver stages.
authors: W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins Malaria Research Institute, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Sze-Wah
authors: SW
authors: Tse
authors: Andrea J
authors: AJ
authors: Radtke
authors: Fidel
authors: F
authors: Zavala
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D000939:Epitopes / Q000276:immunology; D022781:Hepatocytes / Q000469:parasitology*; D006801:Humans; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines