title: Tricomponent complex loaded with a mosquito-stage antigen of the malaria parasite induces potent transmission-blocking immunity.
abstract: The development of malaria vaccines is challenging, partly because the immunogenicity of recombinant malaria parasite antigens is low. We previously demonstrated that parasite antigens integrated into a tricomponent immunopotentiating complex increase antiparasitic immunity. In this study, the B domains of a group G Streptococcus (SpG) strain and Peptostreptococcus magnus (PpL) were used to evaluate whether vaccine efficacy is influenced by the type of immunoglobulin-binding domain (IBD) in the tricomponent complex. IBDs were fused to a pentameric cartilage oligomeric matrix protein (COMP) to increase the binding avidity of the complexes for their targets. The COMP-IBD fusion proteins generated (COMP-SpG and COMP-PpL and the previously constructed COMP-Z) bound a large fraction of splenic B lymphocytes but not T lymphocytes. These carrier molecules were then loaded with an ookinete surface protein of Plasmodium vivax, Pvs25, by chemical conjugation. The administration of the tricomponent complexes to mice induced more Pvs25-specific serum IgG than did the unloaded antigen. The PpL complex, which exhibited a broad Ig-binding spectrum, conferred higher vaccine efficacy than did the Z or SpG complexes when evaluated with a membrane feed assay. This study demonstrates that this tricomponent immunopotentiating system, incorporating IBDs as the B-lymphocyte-targeting ligands, is a promising technology for the delivery of malaria vaccines, particularly when combined with an aluminum salt adjuvant.
authors: Molecular Microbiology Group, Department of Infectious Diseases, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors: Takeshi
authors: T
authors: Arakawa
authors: Takafumi
authors: T
authors: Tsuboi
authors: Jetsumon
authors: J
authors: Sattabongkot
authors: Kozue
authors: K
authors: Sakao
authors: Motomi
authors: M
authors: Torii
authors: Takeshi
authors: T
authors: Miyata
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D000954:Antigens, Surface / Q000008:administration & dosage / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D064236:Cartilage Oligomeric Matrix Protein / Q000008:administration & dosage / Q000276:immunology; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016780:Malaria, Vivax / Q000517:prevention & control* / Q000635:transmission*; D008807:Mice, Inbred BALB C
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D001426:Bacterial Proteins; D064236:Cartilage Oligomeric Matrix Protein; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C121473:Pvs25 protein, P vivax