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Title: Tricomponent complex loaded with a mosquito-stage antigen of the malaria parasite induces potent transmission-blocking immunity
Authors: Takeshi Arakawa
Takafumi Tsuboi
Jetsumon Sattabongkot
Kozue Sakao
Motomi Torii
Takeshi Miyata
University of the Ryukyus
Ehime University
Mahidol University
Kagoshima University
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology;Medicine
Issue Date: 1-Jan-2014
Citation: Clinical and Vaccine Immunology. Vol.21, No.4 (2014), 561-569
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. Copyright © 2014 American Society for Microbiology. All Rights Reserved.
ISSN: 1556679X
Appears in Collections:Scopus 2011-2015

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