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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

Kim TW, Hung CF, Kim JW, Juang J, Chen PJ, He L et al. Hum Gene Ther 2004;15:167177 

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 antitumour immunity against an E7-expressing tumour 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.


 

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