Cytotoxic T lymphocyte (CTL) low-responsiveness to the Plasmodium falciparum circumsporozoite protein in naturally-exposed endemic populations: analysis of human CTL response to most known variants

Cytotoxic T lymphocytes (CTL) specific for epitope(s) withinthe circumsporozoite (CS) protein of malaria sporozoites havebeen shown to play an important role in protective immunityagainst malaria, at least in murine models. Their role in sporozoiteimmunity in the human host has, however, not yet been elucidated.Immunological non-responsiveness and antigenlc diversity withinT cell epitopes of the CS protein have been identified as potentialproblems in producing a sporozoite vaccine. These factors maycontribute to the widespread lack of sporozoite immunity inendemic populations. In this study, 137 individuals with a historyof natural endemic exposure to falciparum sporozoites (119 residentin north west Thailand and 18 resident in coastal Papua NewGuinea) were tested for a CTL response to the Plasmodium falciparumCS protein Fifty-four overlapping peptides, spanning the entiresequence of the CS protein of P. falciparum including most knownvariants, were studied. While most individuals had antibodiesto the immunodominant B cell repeat, (NANP)_n, and while CTLspecific for an influenza virus matrix synthetic peptide couldbe generated from five of 23 Karen Thai individuals tested,no CS protein-specific CTL could be detected in these populations.Our data have important implications for vaccine programs.