Combined administration with DNA encoding vesicular stomatitis virus G protein enhances DNA vaccine potency.
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.
Mao
Chih-Ping
CP
Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA.
Hung
Chien-Fu
CF
Kang
Tae Heung
TH
He
Liangmei
L
Tsai
Ya-Chea
YC
Wu
Chao-Yi
CY
Wu
T-C
TC
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016923:Cell Death; D002459:Cell Fusion; D002478:Cells, Cultured; D004279:DNA, Viral / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology
D000956:Antigens, Viral; D004279:DNA, Viral; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma