High immunogenicity in chimpanzees of peptides and lipopeptides derived from four new Plasmodium falciparum pre-erythrocytic molecules

We have investigated the immunogenicity in chimpanzees of twelve synthetic peptides derived from four new Plasmodium falciparum molecules expressed at pre-erythrocytic stages of the human malaria parasite. These parasite mole cules were initially selected through their ability to be recognized by sta ge restricted human antibodies. Twelve 20- to 41-mer peptides representing potential human B- or T-cell epitopes were selected from these proteins, an d synthesized. Six of these were modified by a C-terminal lipidic chain in order to re-inforce their immunogenicity. Strong B- and T-helper cell respo nses were induced in chimpanzees by lipopeptides injected without adjuvant and by peptides in Montanide. All twelve peptides induced CD4(+) T-cell pro liferative responses, as well as the secretion of IFN-gamma (some of them a t very high levels) and eleven peptides induced antibody responses. The imm une responses elicited in this way were reactive with native parasite prote ins, as shown by recall studies with sporozoite stage proteins, and proved to be long-lasting (up to 10 months after immunization). Our results suppor t the strategy employed to select these four new malarial antigens and the corresponding peptides, and suggest that the immunizing formulations are bo th efficient and clinically acceptable. (C) 2000 Elsevier Science Ltd, All rights reserved.