title: Opsonization by antigen-specific antibodies as a mechanism of protective immunity induced by Plasmodium falciparum circumsporozoite protein-based vaccine.
abstract: Recently conducted trials involving the Plasmodium falciparum circumsporozoite (CS) protein-based RTS,S malaria vaccine yielded unprecedented protection against a challenge with infectious sporozoites (spzs). The RTS,S vaccine induced high titres of CS protein-specific antibodies (Abs) in many of the protected volunteers, but the contribution of these Abs to protection remains unknown. Because opsonization by Ab promotes the uptake and destruction of spzs by monocytes and macrophages in both rodent and primate malaria, we asked if the RTS,S-induced Abs have antigen-specific opsonizing activity. Screening plasma from a large number of subjects using spzs was impractical, therefore we developed an alternative assay based on cytofluorometry that allowed the detection of fluoresceinated-Ag-Ab complexes endocytosed by the FcR+ THP-1 human monocyte line. The results showed that plasma samples from RTS,S-immunized subjects contained opsonizing CS protein-specific Abs and the endocytic activity of these Abs in protected subjects was significantly higher than in subjects who were susceptible to infection with spzs. We also demonstrated by electron microscopy that live spzs exposed to RTS,S-immune plasma could be internalized by the THP-1 cells. These results suggest that opsonization by CS protein-specific Abs might be one of the mechanisms that contributes to RTS,S-induced protective immunity.
authors.affiliation: Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Schwenk
authors.forename: Ludmila V
authors.initials: LV
authors.lastname: Asher
authors.forename: Isaac
authors.initials: I
authors.lastname: Chalom
authors.forename: David
authors.initials: D
authors.lastname: Lanar
authors.forename: Peifang
authors.initials: P
authors.lastname: Sun
authors.forename: Katherine
authors.initials: K
authors.lastname: White
authors.forename: Deborah
authors.initials: D
authors.lastname: Keil
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: Jose
authors.initials: J
authors.lastname: Stoute
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: Urszula
authors.initials: U
authors.lastname: Krzych
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D002478:Cells, Cultured; D004705:Endocytosis; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control; D051379:Mice; D009000:Monocytes / Q000276:immunology; D009895:Opsonin Proteins / Q000276:immunology*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology / Q000648:ultrastructure; D014614:Vaccines, Synthetic / Q000276:immunology; D014617:Vacuoles / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D009895:Opsonin Proteins; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan