TY - JOUR
T1 - Strategies for developing multi-epitope, subunit-based, chemically synthesized anti-malarial vaccines
AU - Patarroyo, M. A.
AU - Cifuentes, G.
AU - Bermúdez, A.
AU - Patarroyo, M. A.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/10
Y1 - 2008/10
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1582-4934.2008.00174.x
DO - 10.1111/j.1582-4934.2008.00174.x
M3 - Review article
C2 - 19012725
AN - SCOPUS:44649194624
SN - 1582-1838
VL - 12
SP - 1915
EP - 1935
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 5B
ER -