Cf. Hung et al., Improving vaccine potency through intercellular spreading and enhanced MHCclass I presentation of antigen, J IMMUNOL, 166(9), 2001, pp. 5733-5740
The potency of naked DNA vaccines is limited by their inability to amplify
and spread in vivo. VP22, a HSV-1 protein, has demonstrated the remarkable
property of intercellular transport and may thus provide a unique approach
for enhancing vaccine potency. Therefore, we created a novel fusion of VP22
with a model Ag, human papillomavirus type 16 E7, in a DNA vaccine that ge
nerated enhanced spreading and MHC class I presentation of Ag. These proper
ties led to a dramatic increase in the number of E7-specific CD8(+) T cell
precursors in vaccinated mice (around 50-fold) and converted a less effecti
ve DNA vaccine into one with significant potency against E7-expressing tumo
rs. In comparison, nonspreading VP22(1-267) mutants failed to enhance vacci
ne potency. Our data indicated that the potency of DNA vaccines may be dram
atically improved through intercellular spreading and enhanced MHC class I
presentation of Ag.