Field studies of cytotoxic T lymphocytes in malaria infections: Implications for malaria vaccine development

The search for a cytotoxic T lymphocyte (CTL)-inducing malaria vaccine has moved forward from epitope identification to planning stages of safety and immunogenicity trials of candidate vaccines. Development of CTL-inducing va ccine candidates has taken center stage based on the observation that CTL-m ediated protection might be the dominant mechanism by which sterile immunit y is achieved in irradiated sporozoite immunization experiments in humans a nd laboratory animals. However; studies in naturally infected individuals l iving in endemic areas, as reviewed here by Michael Aidoo and Venkatachalam Udhayakumar, have revealed that CTL induction might be influenced by facto rs such as parasite variants, host genes, other infections and transmission patterns. The influence of these factors on CTL induction has been demonst rated individually and in various combinations in controlled animal experim ents. However, in naturally infected humans, they are presented in a comple x hos-parasite-environment interaction, in a manner that is not easily achi eved in laboratory-based experiments. Understanding these interactions is c rucial for the development and testing of CTL-inducing vaccines for humans.