article
Mapping the anatomy of a Plasmodium falciparum MSP-1 epitope using pseudopeptide-induced mono- and polyclonal antibodies and CD and NMR conformation analysis
Registro en:
ISSN: 1047-8477
EISSN: 1095-8657
Autor
Lozano, José Manuel
Espejo, Fabiola
Ocampo, Marisol
Salazar, Luz Mary
Tovar, Diana
Barrera, Nubia
Guzmán, Fanny
Patarroyo, Manuel Elkin
Institución
Resumen
Antigen structure modulation represents an approach towards designing subunit malaria vaccines. A specific epitope's ? carbon stereochemistry, as well as its backbone topochemistry, was assessed for obtaining novel malarial immunogens. A variety of MSP-138–61 Plasmodium falciparum epitope pseudopeptides derived were synthesised, based on solid-phase pseudopeptide chemistry strategies; these included all-l, all-d, partially-d substituted, all-?-[NH-CO]-Retro, all-?-[NH-CO]-Retro-inverso, and ?-[CH2NH] reduced amide surrogates. We demonstrate that specific recombinant MSP-134–469 fragment binding to red blood cells (RBCs) is specifically inhibited by non-modified MSP-142–61, 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.