Redefining an epitope of a malaria vaccine candidate, with antibodies against the N-terminal MSA-2 antigen of Plasmodium harboring non-natural peptide bonds

The aim of obtaining novel vaccine candidates against malaria and other transmissible diseases can be partly based on selecting non-polymorphic peptides from relevant antigens of pathogens, which have to be then precisely modified for inducing a protective immunity against the disease. Bearing in mi...

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Autores:
Tipo de recurso:
Fecha de publicación:
2013
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/24274
Acceso en línea:
https://doi.org/10.1007/s00726-013-1541-x
https://repository.urosario.edu.co/handle/10336/24274
Palabra clave:
Epitope
Immunoglobulin antibody
Immunoglobulin class
Malaria vaccine
Merozoite surface protein 2
Monoclonal antibody
Peptidomimetic agent
Polyclonal antibody
Animal cell
Animal experiment
Animal model
Aotus
Article
Bagg albino mouse
Bioinformatics
Chemical structure
Controlled study
Epitope mapping
Erythrocyte
Female
Infrared spectroscopy
Mouse
Nonhuman
Parasitemia
Passive immunization
Peptide synthesis
Plasmodium
Plasmodium berghei
Plasmodium berghei infection
Plasmodium falciparum
Plasmodium yoelii
Plasmodium yoelii infection
Priority journal
Proton nuclear magnetic resonance
Solid phase synthesis
Mus
Plasmodium falciparum
Rodentia
Antigen-antibody reactions
Computational biology
Epitopes
Malaria vaccines
Plasmodium falciparum
Protozoan proteins
Antibody
Malaria vaccine candidate
Passive immunization
Peptide mimetic
Peptide-bond isostere
Site-directed design
monoclonal
protozoan
Antibodies
Antigens
Rights
License
Abierto (Texto Completo)
Description
Summary:The aim of obtaining novel vaccine candidates against malaria and other transmissible diseases can be partly based on selecting non-polymorphic peptides from relevant antigens of pathogens, which have to be then precisely modified for inducing a protective immunity against the disease. Bearing in mind the high degree of the MSA-221-40 peptide primary structure's genetic conservation among malaria species, and its crucial role in the high RBC binding ability of Plasmodium falciparum (the main agent causing malaria), structurally defined probes based on non-natural peptide-bond isosteres were thus designed. Thus, two peptide mimetics were obtained (so-called reduced amide pseudopeptides), in which naturally made amide bonds of the 30FIN32-binding motif of MSA-2 were replaced with ?-[CH2-NH] methylene amide isostere bonds, one between the F-I and the second between I-N amino acid pairs, respectively, coded as ?-128 ?-130. These peptide mimetics were used to produce poly- and monoclonal antibodies in Aotus monkeys and BALB/c mice. Parent reactive mice-derived IgM isotype cell clones were induced to Ig isotype switching to IgG sub-classes by controlled in vitro immunization experiments. These mature isotype immunoglobulins revealed a novel epitope in the MSA-225-32 antigen and two polypeptides of rodent malaria species. Also, these antibodies' functional activity against malaria was tested by in vitro assays, demonstrating high efficacy in controlling infection and evidencing neutralizing capacity for the rodent in vivo malaria infection. The neutralizing effect of antibodies induced by site-directed designed peptide mimetics on Plasmodium's biological development make these pseudopeptides a valuable tool for future development of immunoprophylactic strategies for controlling malarial infection. © 2013 The Author(s).