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J Immunol ; 172(9): 5561-9, 2004 May 01.
Article in English | MEDLINE | ID: mdl-15100299

ABSTRACT

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-gamma 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-gamma responses, whereas, CD8(+) T cells were involved only in the production phase. IFN-gamma 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.


Subject(s)
Antibodies, Protozoan/biosynthesis , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Immunization Schedule , Malaria Vaccines/administration & dosage , Plasmodium falciparum/immunology , Protozoan Proteins/administration & dosage , Vaccines, DNA/administration & dosage , Amino Acid Sequence , Animals , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cytotoxicity Tests, Immunologic , Epitopes, T-Lymphocyte/administration & dosage , Epitopes, T-Lymphocyte/immunology , Hepatitis B Antibodies/biosynthesis , Hepatitis B Surface Antigens/immunology , Humans , Immunization, Secondary/methods , Interferon-gamma/biosynthesis , Malaria Vaccines/genetics , Malaria Vaccines/immunology , Malaria, Falciparum/immunology , Malaria, Falciparum/prevention & control , Molecular Sequence Data , Protozoan Proteins/genetics , Protozoan Proteins/immunology , T-Lymphocyte Subsets , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Vaccines, DNA/genetics , Vaccines, DNA/immunology
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