Induction in Humans of CD8+ and CD4+ T Cell and Antibody Responses by Sequential Immunization with Malaria DNA and Recombinant Protein

摘要

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.