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

Peifang Sun, Robert Schwenk, Katherine White, Jose A. Stoute, Joe Cohen, W. Ripley Ballou, Gerald Voss, Kent E. Kester, D. Gray Heppner, Urszula Krzych

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192 Scopus citations

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-γ reactivity of pre- and RTS,S-immune lymphocytes from 20 subjects vaccinated with RTS,S. We observed elevated IFN-γ in subjects protected by RTS,S; moreover, both CD4+ and CD8+ T cells produced IFN-γ in response to CS protein peptides. Significantly, protracted protection, albeit observed only in two of seven subjects, was associated with sustained IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)6961-6967
Number of pages7
JournalJournal of Immunology
Volume171
Issue number12
StatePublished - Dec 15 2003

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Sun, P., Schwenk, R., White, K., Stoute, J. A., Cohen, J., Ballou, W. R., Voss, G., Kester, K. E., Heppner, D. G., & Krzych, U. (2003). Protective Immunity Induced with Malaria Vaccine, RTS,S, Is Linked to Plasmodium falciparum Circumsporozoite Protein-Specific CD4+ and CD8+ T Cells Producing IFN-γ. Journal of Immunology, 171(12), 6961-6967.