Evidence supporting the hypothesis that specifically modifying a malaria peptide to fit into HLA-DRbeta1*03 molecules induces antibody production and protection.
EBA-175 protein is used as ligand in Plasmodium falciparum binding to erythrocytes. Evidence shows that conserved peptide 1815 from this protein having high red blood cell binding ability plays an important role in the invasion process. This peptide is neither immunogenic nor protective. Residues were substituted by amino acids having similar volume or mass but different polarity in 1815 analogues had to make them fit into HLA-DRbeta1*03 molecules; these were synthesised and inoculated into Aotus monkeys, generating different immunogenic and/or protective immune responses. A shortening in alpha-helix structure was found in the immunogenic and protective ones when their secondary structure was analyzed by NMR to correlate their structure with their immunological properties. This data, together with results from previous studies, suggests that this shortening in high-activity binding peptide (HABP) helical configuration may lead to better fitting into immune system molecules as shown by binding to purified HLA-DRbeta1* molecules rendering them immunogenic and protective and therefore, excellent candidates for consideration as components of a subunit based multi-component synthetic vaccine against malaria.
Cifuentes
Gladys
G
Fundación Instituto de Inmunología de Colombia (FIDIC), Cra. 50, No. 26-00, Bogotá, Colombia.
Salazar
Luz Mary
LM
Vargas
Luis Eduardo
LE
Parra
Carlos Alberto
CA
Vanegas
Magnolia
M
Cortes
Jimena
J
Patarroyo
Manuel Elkin
ME
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D001029:Aotus trivirgatus; D001666:Binding Sites, Antibody; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D008288:Malaria / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000276:immunology
D000913:Antibodies, Protozoan; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments