Journal
CLINICAL AND VACCINE IMMUNOLOGY
Volume 21, Issue 4, Pages 561-569Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/CVI.00053-14
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI [20590425, 23590490, 23117008]
- Japan Society for the Promotion of Science (JSPS) KAKENHI in Japan [23406007]
- Program for the Promotion of Basic Research Activities for Innovative Biosciences from the Bio-oriented Technology Research Advancement Institution of Japan
- Institute of Tropical Medicine, Nagasaki University, Japan
- Grants-in-Aid for Scientific Research [20590425, 23406007, 26670202, 23590490, 26253026] Funding Source: KAKEN
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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.
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