Strategies for developing multi-epitope, subunit-based, chemically synthesized anti-malarial vaccines Academic Article

abstract

  • 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 immun genic or protection-inducing when used for immunizing Aotus monkeys. Modifying some critical binding residues in these high-activi binding peptides' (HABPs') attachment to red blood cells (RBC) allowed them to induce immunogenicity and protection against expermental challenge and acquire the ability to bind to specific HLA-DRp1* alleles. These modified HABPs adopted certain characterist structural configurations as determined by circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) associated with certain HLA-DRβ1* haplotype binding activities and characteristics, such as a 2-Å-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 haplotyp 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. © 2007 The Authors.

publication date

  • 2008/10/1

edition

  • 12

keywords

  • Alleles
  • Amino Acids
  • Antigens
  • Antimalarials
  • Circular Dichroism
  • Epitopes
  • Erythrocytes
  • HLA-DR Antigens
  • Haplorhini
  • Haplotypes
  • Magnetic Resonance Spectroscopy
  • Malaria
  • Malaria Vaccines
  • Parasites
  • Peptides
  • Plasmodium falciparum
  • Proteins
  • Synthetic Vaccines

International Standard Serial Number (ISSN)

  • 1582-1838

number of pages

  • 21

start page

  • 1915

end page

  • 1935