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

Citation
L. Benmohamed et al., High immunogenicity in chimpanzees of peptides and lipopeptides derived from four new Plasmodium falciparum pre-erythrocytic molecules, VACCINE, 18(25), 2000, pp. 2843-2855
Citations number
61
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Veterinary Medicine/Animal Health",Immunology
Journal title
VACCINE
ISSN journal
0264-410X → ACNP
Volume
18
Issue
25
Year of publication
2000
Pages
2843 - 2855
Database
ISI
SICI code
0264-410X(20000615)18:25<2843:HIICOP>2.0.ZU;2-9
Abstract
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.