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The Journal of Immunology, 2003, 171: 6961-6967.
Copyright © 2003 by The American Association of Immunologists

Protective Immunity Induced with Malaria Vaccine, RTS,S, Is Linked to Plasmodium falciparum Circumsporozoite Protein-Specific CD4+ and CD8+ T Cells Producing IFN-{gamma}1

Peifang Sun*, Robert Schwenk*, Katherine White*, Jose A. Stoute*, Joe Cohen{dagger}, W. Ripley Ballou*,{dagger}, Gerald Voss{dagger}, Kent E. Kester*, D. Gray Heppner* and Urszula Krzych2,*

* Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910; and {dagger} GlaxoSmithKline-Biologicals, Rixensart, Belgium

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.




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