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 molecules were initially selected through their ability to be recognized by stage restricted human antibodies. Twelve 20- to 41-mer peptides representing potential human B- or T-cell epitopes were selected from these proteins, and 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 responses were induced in chimpanzees by lipopeptides injected without adjuvant and by peptides in Montanide. All twelve peptides induced CD4(+) T-cell proliferative responses, as well as the secretion of IFN-gamma (some of them at very high levels) and eleven peptides induced antibody responses. The immune responses elicited in this way were reactive with native parasite proteins, as shown by recall studies with sporozoite stage proteins, and proved to be long-lasting (up to 10 months after immunization). Our results support the strategy employed to select these four new malarial antigens and the corresponding peptides, and suggest that the immunizing formulations are both efficient and clinically acceptable.
Benmohamed
L
L
Unité de Parasitologie Bio-Médicale, Institut Pasteur, Paris, France.
Thomas
A
A
Bossus
M
M
Brahimi
K
K
Wubben
J
J
Gras-Masse
H
H
Druilhe
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001666:Binding Sites, Antibody; D003429:Cross Reactions; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008074:Lipoproteins / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008213:Lymphocyte Activation / Q000276:immunology; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology*; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D010963:Plasmodium falciparum / Q000737:chemistry / Q000254:growth & development* / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D011897:Random Allocation; D013601:T-Lymphocytes / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D008074:Lipoproteins; D010455:Peptides; D015800:Protozoan Proteins; C067302:liver stage-specific antigen, Plasmodium; D007371:Interferon-gamma