Fitting modified HRP-I peptide analogue 3D structure into HLA-DR molecules induces protection against Plasmodium falciparum malaria.
Conserved, high-activity, red blood cell binding malaria peptide 6786, from the HRP-I protein, having a random 3D structure as determined by 1H-NMR, was non-immunogenic and non-protection inducing when used as an immunogen in Aotus monkeys. Modifications made in its amino acid sequence were thus performed to render it immunogenic and protection inducing. Non-immunogenic, non-protection inducing modified peptide 13852 presented A2-H8 and K14-L18 helix fragments. Immunogenic, non-protection inducing modified peptide 23428 presented a short, displaced helix in a different region, whilst immunogenic, protection inducing peptide 24224 had 2 displaced helical regions towards the central region giving more flexibility to its N- and C-terminals. Immunogenic and protection inducing peptides bound with high affinity to HLA-DRB1* 0301 whilst others did not bind to any HLA-DRB1* purified molecule. Structural modifications may thus lead to inducing immunogenicity and protection associated with their capacity to bind specifically to purified HLA-DRB1* molecules, suggesting a new way of developing multi-component, subunit-based malarial vaccines.
Bermúdez
Adriana
A
Fundación Instituto de Inmunología de Colombia (FIDIC), Cra 50 No. 26-00, Bogotá, Colombia.
Alba
Patricia
P
Espejo
Fabiola
F
Vargas
Luis Eduardo
LE
Parra
Carlos
C
Rodríguez
Raúl
R
Reyes
Claudia
C
Patarroyo
Manuel Elkin
ME
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D016645:Aotidae / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*
D000953:Antigens, Protozoan; D006684:HLA-DR Antigens; D017780:Malaria Vaccines; D009842:Oligopeptides; D010455:Peptides; D015800:Protozoan Proteins; C042968:knob protein, Plasmodium falciparum