title: Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium falciparum circumsporozoite protein-specific CD4+ and CD8+ T cells producing IFN-gamma.
abstract: The Plasmodium falciparum circumsporozoite (CS) protein-based pre-erythrocytic stage vaccine, RTS,S, induces a high level of protection against experimental sporozoite challenge. The immune mechanisms that constitute protection are only partially understood, but are presumed to rely on Abs and T cell responses. In the present study we compared CS protein peptide-recalled IFN-gamma reactivity of pre- and RTS,S-immune lymphocytes from 20 subjects vaccinated with RTS,S. We observed elevated IFN-gamma in subjects protected by RTS,S; moreover, both CD4(+) and CD8(+) T cells produced IFN-gamma in response to CS protein peptides. Significantly, protracted protection, albeit observed only in two of seven subjects, was associated with sustained IFN-gamma response. This is the first study demonstrating correlation in a controlled Plasmodia sporozoite challenge study between protection induced by a recombinant malaria vaccine and Ag-specific T cell responses. Field-based malaria vaccine studies are in progress to validate the establishment of this cellular response as a possible in vitro correlate of protective immunity to exo-erythrocytic stage malaria vaccines.
authors.affiliation: Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Peifang
authors.initials: P
authors.lastname: Sun
authors.forename: Robert
authors.initials: R
authors.lastname: Schwenk
authors.forename: Katherine
authors.initials: K
authors.lastname: White
authors.forename: Jose A
authors.initials: JA
authors.lastname: Stoute
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: Urszula
authors.initials: U
authors.lastname: Krzych
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma