Protection against experimental malaria associated with AMA-1 peptide analogue structures.
One Plasmodium falciparum malaria antigen is an integral membrane protein called apical membrane antigen-1. High activity binding peptides to human red blood cells have been identified in this protein. 4337 is a conserved, non-immunogenic peptide with high activity red blood cell binding and its critical residues have already been identified. Peptide analogues (with amino acids having the same mass but different charge) were generated to change their immunogenic and protective characteristics. Three analogues having positive or negative immunological results were studied by nuclear magnetic resonance. The studied peptides all had an alpha-helix fragment, but in different peptide regions and extensions, except for randomly structured 4337. We show that altering a few amino acids induced immunogenicity and protectivity against experimental malaria and changed their three-dimensional structure, suggesting a better fit with immune system molecules and that modified peptides having better immunological properties can be included in the design of new malaria multi-component subunit-based vaccine.
Salazar
Luz M
LM
Fundación Instituto de Inmunologi;a de Colombia (FIDIC), Universidad Nacional de Colombia, Carrera 50 No. 26-00, Bogotá, Colombia. mepatarr@mail.com
Alba
Martha P
MP
Torres
Maria H
MH
Pinto
Martha
M
Cortes
Ximena
X
Torres
Libardo
L
Patarroyo
Manuel E
ME
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan; D000882:Haplorhini; D009682:Magnetic Resonance Spectroscopy; D017780:Malaria Vaccines / Q000737:chemistry / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D010455:Peptides; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium