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DNA Vaccines, Combining Form of Antigen and Method of Delivery to Raise a Spectrum of IFN- and IL-4-Producing CD4⁺ and CD8⁺ T Cells¹

Alp E. Oran^*, and Harriet L. Robinson^2,*,

^* Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322

DNA-based immunizations have been used to determine the patterns of type 1 and type 2 cytokines that can be induced in vivo for Ag-specific CD4⁺ and CD8⁺ T cells. IL-4 was used as a signature cytokine for a type 2 T cell response and IFN- as the signature cytokine for a type 1 response. Gene gun deliveries of secreted Ags were used to bias responses toward type 2 and saline injections of cell-associated Ags to bias responses toward type 1. The studies revealed that gene gun bombardments of DNAs expressing secreted Ags strongly biased responses toward type 2, inducing IL-4-producing CD8⁺ as well as CD4⁺ T cells. Saline injections of DNAs expressing cell-associated Ags strongly biased responses toward type 1, inducing IFN--producing CD8⁺ and CD4⁺ cells. A mixed type 1/type 2 response of IFN--producing CD8⁺ T cells and IL-4-producing CD4⁺ T cells was found for gene gun deliveries of cell-associated Ags. Saline injections of secreted Ags raised a weakly type 1-biased response characterized by only slightly higher frequencies of IFN-- than IL-4-producing CD4⁺ and CD8⁺ T cells. Studies in B cell knockout and hen egg lysozyme Ig transgenic mice revealed that B cells were required for the generation of IL-4-producing CD8⁺ T cells.

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