Protecting capacity against malaria of chemically defined tetramer forms based on the Plasmodium falciparum apical sushi protein as potential vaccine components

Developing novel generations of subunit-based antimalarial vaccines in the form of chemically-defined macromolecule systems for multiple antigen presentation represents a classical problem in the field of vaccine development. Many efforts involving synthesis strategies leading to macromolecule constructs have been based on dendrimer-like systems, the condensation of large building blocks and conventional asymmetric double dimer constructs, all based on lysine cores. This work describes novel symmetric double dimer and condensed linear constructs for presenting selected peptide multi-copies from the apical sushi protein expressed in Plasmodium falciparum. These molecules have been proved to be safe and innocuous, highly antigenic and have shown strong protective efficacy in rodents challenged with two Plasmodium species. Insights into systematic design, synthesis and characterisation have led to such novel antigen systems being used as potential platforms for developing new anti-malarial vaccine candidates. © 2014 Elsevier Inc. All rights reserved.

• Fecha de publicación: 2014
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23514
• Acceso en línea: https://doi.org/10.1016/j.bbrc.2014.06.143; https://repository.urosario.edu.co/handle/10336/23514
• Palabra clave: Antimalarial agent; Antimalarial vaccine; Dendrimer; Dimer; Iodine 125; Peptide fragment; Plasmodium falciparum apical sushi protein; Protozoal protein; Protozoal vaccine; Tetramer; Unclassified drug; Aminocaproic acid derivative; Epitope; Malaria vaccine; Parasite antigen; Peptide; Subunit vaccine; Amino acid sequence; Animal experiment; Animal model; Antigen presenting cell; Article; Chemical structure; Controlled study; Cytotoxicity; Drug design; Drug synthesis; Gene mutation; Hemolysis; Hypothesis; Immunochemistry; In vitro study; Isotope labeling; Macromolecule; Malaria control; Merozoite; Mouse; Nonhuman; Nucleotide sequence; Parasitemia; Peptide synthesis; Physical chemistry; Plasmodium berghei infection; Plasmodium falciparum; Plasmodium yoelii infection; Priority journal; Protein expression; Protein secondary structure; Sequence analysis; Target cell; Vaccination; Western blotting; Animal; Bagg albino mouse; Chemistry; Human; Immunology; Malaria; Metabolism; Molecular genetics; Pathogenicity; Plasmodium berghei; Plasmodium falciparum; Plasmodium yoelii; Protein conformation; Protein multimerization; Rabbit; Plasmodium falciparum; Rodentia; Amino acid sequence; Aminocaproates; Animals; Epitopes; Humans; Malaria; Malaria vaccines; Mice; Molecular sequence data; Peptides; Plasmodium berghei; Plasmodium falciparum; Plasmodium yoelii; Protein conformation; Protein multimerization; Rabbits; Antimalarial-vaccine; Dendrimer; Macromolecule; Pfasp; Plasmodium; falciparum; falciparum; inbred balb c; molecular; protozoan; subunit; Malaria; Antigens; Malaria; Mice; Models; Vaccines
• License: Abierto (Texto Completo)