Vaccination with a DNA Vaccine Encoding Herpes Simplex Virus Type 1 VP22 Linked to Antigen Generates Long-Term Antigen-Specific CD8-Positive Memory T Cells and Protective Immunity

Abstract

Intradermal vaccination with DNA encoding herpes simplex virus type 1 (HSV-1) VP22 linked to antigen leads to spread of antigen within the epithelium and results in enhanced antigen-specific CD8⁺ T cell immune responses in vaccinated mice. In this study, we characterized the number of antigen-expressing dendritic cells (DCs) in the draining lymph nodes of vaccinated mice and determined whether the linkage of VP22 to antigen would influence the ability of antigen-expressing DCs to activate antigen-specific CD8⁺ T cells in vivo. Vaccination with DNA encoding HSV-1 VP22 linked to human papillomavirus type 16 E7 antigen generated more antigen-expressing DCs in the draining lymph nodes of vaccinated mice than E7 alone. In addition, the linkage of VP22 to E7 improved the MHC class I presentation of E7 in transfected DCs and led to enhanced activation of E7-specific CD8⁺ T cells. We also observed that vaccination with DNA encoding VP22 linked to E7 generated more E7-specific CD8⁺ memory T cells, and enhanced long-term protective antitumor immunity against an E7-expressing tumor in vaccinated mice compared with vaccination with DNA encoding E7 alone. Thus, administration of DNA encoding VP22 linked to antigen represents a plausible approach for the development of protective DNA vaccines.