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

• Published in: The Journal of immunology (1950) Vol. 171; no. 12; pp. 6961 - 6967
• Main Authors: Sun, Peifang, Schwenk, Robert, White, Katherine, Stoute, Jose A., Cohen, Joe, Ballou, W. Ripley, Voss, Gerald, Kester, Kent E., Heppner, D. Gray, Krzych, Urszula
• Format: Journal Article
• Language: English
• Published: United States 15.12.2003
• Subjects: Amino Acid Sequence; Animals; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cells, Cultured; Epitopes, T-Lymphocyte - immunology; Humans; Immunization, Secondary; Immunologic Memory; Interferon-gamma - biosynthesis; Malaria Vaccines - administration & dosage; Malaria Vaccines - immunology; Malaria, Falciparum - immunology; Malaria, Falciparum - prevention & control; Molecular Sequence Data; Plasmodium falciparum - immunology; Protozoan Proteins - administration & dosage; Protozoan Proteins - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.12.6961

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.