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* Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910;
Henry M. Jackson Foundation, Rockville, MD 20852;
GlaxoSmithKline, Rixensart, Belgium;
Malaria Vaccine Program, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910; and
¶ Vical Incorporated, San Diego, CA 92121
Vaccine-induced protection against diseases like malaria, AIDS, and cancer may require induction of Ag-specific CD8+ and CD4+ T cell and Ab responses in the same individual. In humans, a recombinant Plasmodium falciparum circumsporozoite protein (PfCSP) candidate vaccine, RTS,S/adjuvant system number 2A (AS02A), induces T cells and Abs, but no measurable CD8+ T cells by CTL or short-term (ex vivo) IFN-
ELISPOT assays, and partial short-term protection. P. falciparum DNA vaccines elicit CD8+ T cells by these assays, but no protection. We report that sequential immunization with a PfCSP DNA vaccine and RTS,S/AS02A induced PfCSP-specific Abs and Th1 CD4+ T cells, and CD8+ cytotoxic and Tc1 T cells. Depending upon the immunization regime, CD4+ T cells were involved in both the induction and production phases of PfCSP-specific IFN- responses, whereas, CD8+ T cells were involved only in the production phase. IFN- mRNA up-regulation was detected in both CD45RA– (CD45RO+) and CD45RA+CD4+ and CD8+ T cell populations after stimulation with PfCSP peptides. This finding suggests CD45RA+ cells function as effector T cells. The induction in humans of the three primary Ag-specific adaptive immune responses establishes a strategy for developing immunization regimens against diseases in desperate need of vaccines.
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