Mapping the anatomy of a Plasmodium falciparum MSP-1 epitope using pseudopeptide-induced mono- and polyclonal antibodies and CD and NMR conformation analysis.
Antigen structure modulation represents an approach towards designing subunit malaria vaccines. A specific epitope's alpha carbon stereochemistry, as well as its backbone topochemistry, was assessed for obtaining novel malarial immunogens. A variety of MSP-1(38-61) Plasmodium falciparum epitope pseudopeptides derived were synthesised, based on solid-phase pseudopeptide chemistry strategies; these included all-L, all-D, partially-D substituted, all-Psi-[NH-CO]-Retro, all-Psi-[NH-CO]-Retro-inverso, and Psi-[CH2NH] reduced amide surrogates. We demonstrate that specific recombinant MSP-1(34-469) fragment binding to red blood cells (RBCs) is specifically inhibited by non-modified MSP-1(42-61), as well as by its V52-L53, M51-V52 reduced amide surrogates and partial-D substitutions in K48 and E49. In vivo tests revealed that reduced amide pseudopeptide-immunised Aotus monkeys induced neutralising antibodies specifically recognising the MSP-1 N-terminus region. These findings support the role of molecular conformation in malaria vaccine development.
Lozano
José Manuel
JM
Fundación Instituto de Inmunología de Colombia, Carrera 50 No. 26-00, Bogotá. jm_lozano@fidic.org.co
Espejo
Fabiola
F
Ocampo
Marisol
M
Salazar
Luz Mary
LM
Tovar
Diana
D
Barrera
Nubia
N
Guzmán
Fanny
F
Patarroyo
Manuel Elkin
ME
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000276:immunology; D016645:Aotidae; D002942:Circular Dichroism; D018604:Epitope Mapping; D004912:Erythrocytes / Q000378:metabolism; D007114:Immunization; D009682:Magnetic Resonance Spectroscopy; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1; D010455:Peptides