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Improving Vaccine Potency Through Intercellular Spreading and Enhanced MHC Class I Presentation of Antigen¹

Chien-Fu Hung^2,*, Wen-Fang Cheng^2,*,¶, Chee-Yin Chai^*, Keng-Fu Hsu^*, Liangmei He^*, Morris Ling^* and T.-C. Wu^3,*,,,

Departments of ^* Pathology, Obstetrics and Gynecology, Molecular Microbiology and Immunology, and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21205; and ^¶ Department of Obstetrics and Gynecology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan

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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