Wang, R., Epstein, J., Charoenvit, Y., Baraceros, F. M., Rahardjo, N., Gay, T., Banania, J. G., Chattopadhyay, R., de la Vega, P., Richie, T. L., Tornieporth, N., Doolan, D. L., Kester, K. E., Heppner, D. G., Norman, J., Carucci, D. J., Cohen, J. D., Hoffman, S. L.
Induction In Humans of CD8+ and CD4+ T Cell and Antibody Responses by Sequential Immunization With Malaria DNA and Recombinant Protein
J Immunol. 2004 May 01; 172(9): 5561-9.
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.