RÉSUMÉ
A mixture of DNA plasmids expressing five Plasmodium falciparum pre-erythrocyte-stage antigens was administered with or without a DNA plasmid encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF) as an immune enhancer. After DNA immunization, antigen-specific gamma interferon (IFN-gamma) responses were detected by ELISPOT in 15/31 volunteers to multiple class I- and/or class II-restricted T-cell epitopes derived from all five antigens. Responses to multiple epitopes (
Sujet(s)
Antigènes de protozoaire/immunologie , Interféron gamma/sang , Vaccins contre le paludisme/immunologie , Paludisme à Plasmodium falciparum/immunologie , Plasmodium falciparum/immunologie , Vaccins à ADN/immunologie , Animaux , Antigènes de protozoaire/administration et posologie , Antigènes de protozoaire/génétique , Morsures et piqûres , Culicidae , Facteur de stimulation des colonies de granulocytes et de macrophages/administration et posologie , Facteur de stimulation des colonies de granulocytes et de macrophages/génétique , Facteur de stimulation des colonies de granulocytes et de macrophages/immunologie , Humains , Immunisation , Vaccins contre le paludisme/administration et posologie , Plasmides , Lymphocytes T/immunologie , Résultat thérapeutique , Vaccins à ADN/administration et posologieRÉSUMÉ
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.