Combined administration with DNA encoding vesicular stomatitis virus G protein enhances DNA vaccine potency

Chih Ping Mao, Chien Fu Hung, Tae Heung Kang, Liangmei He, Ya Chea Tsai, Chao Yi Wu, T. C. Wu

Research output: Contribution to journalArticlepeer-review

Abstract

DNA vaccines have recently emerged at the forefront of approaches to harness the immune system in the prevention and treatment of viral infections, as well as the prevention and treatment of cancers. However, these vaccines suffer from limited efficacy since they often fail to produce significant antigen-specific CD8+ T-cell responses. We report here a novel concept for DNA vaccine design that exploits the unique and powerful ability of viral fusogenic membrane glycoproteins (FMGs) to couple concentrated antigen transfer to dendritic cells (DCs) with local induction of the acute inflammatory response. Intramuscular administration into mice by electroporation technology of a plasmid containing the FMG gene from vesicular stomatitis virus (VSV-G) - together with DNA encoding the E7 protein of human papillomavirus type 16, a model cervical cancer antigen - elicited robust E7-specific CD8+ T-cell responses, as well as therapeutic control of E7-expressing tumors. This effect could potentially be mediated through the immunogenic form of cellular fusion and necrosis induced by VSV-G, which in a concerted fashion provokes leukocyte infiltration into the inoculation site, enhances cross-presentation of antigen to DCs, and stimulates them to mature efficiently. Thus, the incorporation of FMGs into DNA vaccines holds promise for the successful control of viral infections and cancers in the clinic.

Original languageEnglish (US)
Pages (from-to)2331-2339
Number of pages9
JournalJournal of virology
Volume84
Issue number5
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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