Structural characterisation of sporozoite components for a multistage, multi-epitope, anti-malarial vaccine.
A totally effective anti-malarial vaccine must contain epitopes derived from multiple proteins found in different stages of the particular parasite involved in invasion. It must therefore include sporozoite molecules able to induce protective immunity thereby blocking the parasite's access to hepatic cells; thrombospondin-related anonymous protein (TRAP) is one of them. Conserved high activity binding peptides (HABPs) attaching themselves to hepatic cells were used in immunisation studies with the highly malaria-susceptible Aotus monkey. However, they had to be modified to render them immunogenic. The changes induced in lead peptide 3D structure were analysed by correlating such substitutions with the induction of high anti-sporozoite antibody levels in the experimental monkey model. The modification induced structural changes in most modified HABPs, changing them from random-coil or distorted type III beta-turn structures to classical type III or III' beta-turn, thereby allowing a better fit into the MHC-II-peptide-TCR complex since they bound with high affinity to purified HLA-DRbeta1* molecules. These are the first (TRAP) conserved HABPs corresponding to functionally active amino acid sequences in sporozoite invasion and mobility which, when modified, were able to induce very high anti-sporozoite antibody responses, leading to suggesting them as components in the first line of defence of a fully-effective, subunit-based, multi-epitope, multi-stage, synthetic anti-malarial vaccine.
Patarroyo
Manuel E
ME
Fundación Instituto de Inmunología de Colombia, Carrera 50 No. 26-00 Bogotá, Colombia. mepatarr@mail.com
Cifuentes
Gladys
G
Rodríguez
Raúl
R
D000818:Animals; D016645:Aotidae; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D017780:Malaria Vaccines / Q000737:chemistry / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000166:cytology / Q000276:immunology*; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D034101:Sporozoites / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D006684:HLA-DR Antigens; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan