Journal
JOURNAL OF IMMUNOLOGY
Volume 166, Issue 9, Pages 5733-5740Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.166.9.5733
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Funding
- NCI NIH HHS [R01 CA72631-01, U19 CA 72108-02, R01 CA83706-01] Funding Source: Medline
- PHS HHS [5 POL 34582-01] Funding Source: Medline
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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 generated enhanced spreading and MHC class I presentation of Ag. These properties 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 effective DNA vaccine into one with significant potency against E7-expressing tumors. In comparison, nonspreading VP22(1-267) mutants failed to enhance vaccine potency. Our data indicated that the potency of DNA vaccines may be dramatically improved through intercellular spreading and enhanced MHC class I presentation of Ag.
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