title: Vaccination with Altered Peptide Ligands of aPlasmodium bergheiCircumsporozoite Protein CD8 T-Cell Epitope: A Model to Generate T Cells Resistant to Immune Interference by Polymorphic Epitopes.
abstract: Many pathogens, including the malaria parasitePlasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell epitope from the circumsporozoite protein (CS) ofPlasmodium berghei(SYIPSAEKI), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive altered peptide ligand (APL) epitopes (SYIPSAEDI or SYIPSAEAI) has radically different effects on immunity. Hence, co-immunization or sequential stimulationin vivoof SYIPSAEKI with its APL antagonist SYIPSAEDI decreases immunity to both epitopes. By contrast, co-immunization with SYIPSAEAI has no apparent initial effect, but it renders the immune response to SYIPSAEKI resistant to being turned off by subsequent immunization with SYIPSAEDI. These results suggest a novel strategy for vaccines that target polymorphic epitopes potentially capable of mutual immune interference in the field, by initiating an immune response by co-immunization with the desired index epitope, together with a carefully selected "potentiator" APL peptide.
authors.affiliation: Vaccine and Infectious Diseases Laboratory, Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia; Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Minigo
authors.affiliation: Vaccine and Infectious Diseases Laboratory, Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia; School of Medicine, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.affiliation: Diabetes Laboratory, Department of Immunology and Pathology, Monash University , Melbourne, VIC , Australia.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Slattery
authors.affiliation: Vaccine and Infectious Diseases Laboratory, Department of Immunology and Pathology, Monash University , Melbourne, VIC , Australia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
keywords: Plasmodium; T cell; altered peptide ligand; antagonism; cross-reactivity; dendritic cell; malaria; vaccine