title: Polymeric linear Peptide chimeric vaccine-induced antimalaria immunity is associated with enhanced in vitro antigen loading.
abstract: Immunization of mice with Plasmodium berghei or Plasmodium yoelii synthetic linear peptide chimeras (LPCs) based on the circumsporozoite protein protects against experimental challenge with viable sporozoites. The immunogenicity of LPCs is significantly enhanced by spontaneous polymerization. To better understand the antigenic properties of polymeric antimalarial peptides, we studied the immune responses elicited in mice immunized with a polymer or a monomer of a linear peptide construct specific for P. yoelii and compared the responses of antigen-presenting cells following incubation with both peptide species. Efficient uptake of the polymeric peptide in vitro resulted in higher expression of the coactivation markers CD80, CD40, and CD70 on dendritic cells and higher proinflammatory cytokine production than with the monomeric peptide. Macropinocytosis seems to be the main route used by polymeric peptides internalized by antigen-presenting cells. Spontaneous polymerization of synthetic antimalarial-peptide constructs to target professional antigen-presenting cells shows promise for simple delivery of subunit malaria vaccines.
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors.forename: Luciana M
authors.initials: LM
authors.lastname: Silva-Flannery
authors.forename: Monica
authors.initials: M
authors.lastname: Cabrera-Mora
authors.forename: Megan
authors.initials: M
authors.lastname: Dickherber
authors.forename: Alberto
authors.initials: A
authors.lastname: Moreno
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis; D053282:CD27 Ligand / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D017780:Malaria Vaccines / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010873:Pinocytosis; D010962:Plasmodium berghei / Q000235:genetics / Q000276:immunology*; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology*; D055503:Protein Multimerization / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D053282:CD27 Ligand; D019013:CD40 Antigens; D016207:Cytokines; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan