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

M. E. Patarroyo, G. Cifuentes, A. Bermúdez, M. A. Patarroyo

Resultado de la investigación: Contribución a una revistaArtículo

28 Citas (Scopus)

Resumen

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.
Idioma originalInglés estadounidense
Páginas (desde-hasta)1915-1935
Número de páginas21
PublicaciónJournal of Cellular and Molecular Medicine
Volumen12
N.º5B
DOI
EstadoPublicada - oct 1 2008

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