Strategies for developing multi-epitope, subunit-based, chemically synthesized anti-malarial vaccines.
An anti-malarial vaccine against the extremely lethal Plasmodium falciparum is desperately needed. Peptides from this parasite's proteins involved in invasion and having high red blood cell-binding ability were identified; these conserved peptides were not immunogenic or protection-inducing when used for immunizing Aotus monkeys. Modifying some critical binding residues in these high-activiy binding peptides' (HABPs') attachment to red blood cells (RBC) allowed them to induce immunogenicity and protection against experimental challenge and acquire the ability to bind to specific HLA-DRp1* alleles. These modified HABPs adopted certain characteristic structural configurations as determined by circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) associated with certain HLA-DRbeta1* haplotype binding activities and characteristics, such as a 2-angstroms-distance difference between amino acids fitting into HLA-DRp1 Pockets 1 to 9, residues participating in binding to HLA-DR pockets and residues making contact with the TCR, suggesting haplotype and allele-conscious TCR. This has been demonstrated in HLA-DR-like genotyped monkeys and provides the basis for designing high effective, subunit-based, multi-antigen, multi-stage, synthetic vaccines, for immediate human use, malaria being one of them.
Patarroyo
M E
ME
Fundación Instituto de Inmunólogia de Colombia (FIDIC), Bogotá, Colombia. mepatarr@fidic.org.co
Cifuentes
G
G
Bermúdez
A
A
Patarroyo
M A
MA
D000818:Animals; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D008288:Malaria / Q000235:genetics / Q000276:immunology; D017780:Malaria Vaccines / Q000138:chemical synthesis* / Q000235:genetics / Q000276:immunology; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D022223:Vaccines, Subunit / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D006684:HLA-DR Antigens; D017780:Malaria Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic