Tricomponent complex loaded with a mosquito-stage antigen of the malaria parasite induces potent transmission-blocking immunity.
Clin Vaccine Immunol
; 21(4): 561-9, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24521783
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Malária Vivax
/
Vacinas Antimaláricas
/
Transmissão de Doença Infecciosa
/
Antígenos de Protozoários
/
Antígenos de Superfície
Limite:
Animals
Idioma:
En
Revista:
Clin Vaccine Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Japão