Immune Response of Humans to the Circumsporozoite Protein of Plasmodium falciparum: Limited T Cell Response to the Immunodominant Central Repeat Region

Abstract : Humans naturally exposed to malaria make antibodies to the repeat region of the circumsporozoite (CS) protein. A recombinant DNA and a synthetic peptide subunit vaccine derived from the CS protein of Plasmodium falciparum have shown promise in the protection against experimental, sporozoite induced malaria in humans. Human antibody response to immunization with these vaccines has been inconsistent. A possible explanation for the inconsistent response of humans immunized is that there is some genetic restriction of the human T cell response to (NANP)n. To determine if a T cell epitope on the repeat region stimulated T cell help for this antibody, we used R32tet32, a recombinant construct derived from the repeat region of the circumsporozoite protein of P. falciparum, to stimulate in vitro mononuclear cells from residents of an area hyperendemic for malaria. Three groups differing in the length of time they had resided in a malarious area were studied. The percentage of individuals in each group who had positive antibody responses to R32tet32 increased with increased exposure to malaria. Antibody positivity was not correlated with in vitro lymphocyte proliferation responses to the antigen. Lymphocytes from 79% of the individuals showing serum antibodies to R32tet32 failed to respond in a lymphocyte transformation assay, suggesting that T cell helper activity in these individuals was based upon the recognition of a T cell epitope not located within this peptide. Reprints.