Shortening and modifying the 1513 MSP-1 peptide's alpha-helical region induces protection against malaria.
Immunogenic and protective peptide sequences are of prime importance in the search for an anti-malarial vaccine. The MSP-1 conserved and semi-conserved sequences have been shown to contain red blood cell (RBC) membrane high affinity binding peptides (HABP). HABP 1513 sequence ((42)GYSLFQKEKMVLNEGTSGTA(61)), from this protein's N-terminal, has been shown to possess a T-epitope; however, it did not induce a humoral immune response or complete protection when evaluated in Aotus monkeys. Analogue peptides with critical binding residues replaced by amino acids with similar mass but different charge were synthesised and tested for immunogenicity and protectivity in monkey. NMR studies correlated structural behaviour with biological function. Non-immunogenic and non-protective 1513 native peptide presented a helical fragment between residues L(4) and E(14). C-terminal, 5-residue-shorter, non-immunogenic, non-protective peptide 17894 contained an alpha-helix from Q(6) to L(12) residues. Immunogenic and protective peptide 13946 presented a shorter alpha-helix between K(7) to N(13) residues. These data suggest that changing certain residues permits better peptide fit within the MHC class II-peptide-TCR complex, thus activating the immune system and inducing a protective immune response.
Espejo
Fabiola
F
Fundación Instituto de Inmunología de Colombia (FIDIC), Universidad Nacional de Colombia-Bogotá, Cra. 50 No. 26-00, Bogotá, Colombia.
Bermúdez
Adriana
A
Torres
Elizabeth
E
Urquiza
Mauricio
M
Rodríguez
Raúl
R
López
Yolanda
Y
Patarroyo
Manuel Elkin
ME
D000595:Amino Acid Sequence; D000818:Animals; D016645:Aotidae; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002942:Circular Dichroism; D000939:Epitopes / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D009682:Magnetic Resonance Spectroscopy; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000378:metabolism / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010446:Peptide Fragments; D010455:Peptides / Q000737:chemistry; D010963:Plasmodium falciparum / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000939:Epitopes; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D010455:Peptides