Improving DNA vaccine potency by linking Marek's disease virus type 1 VP22 to an antigen.
We have previously employed an intercellular spreading strategy using herpes simplex virus type 1 (HSV-1) VP22 protein to enhance DNA vaccine potency because DNA vaccines lack the intrinsic ability to amplify in cells. Recently, studies have demonstrated that the protein encoded by UL49 of Marek's disease virus type 1 (MDV-1) exhibits some degree of homology to the HSV-1 VP22 protein and features the property of intercellular transport. We therefore generated a DNA vaccine encoding MDV-1 VP22 linked to a model antigen, human papillomavirus type 16 E7. We demonstrated that compared with mice vaccinated with DNA encoding wild-type E7, mice vaccinated with MDV-1 VP22/E7 DNA exhibited a significant increase in number of gamma-interferon-secreting, E7-specific CD8(+)-T-cell precursors as well as stronger tumor prevention and treatment effects. Furthermore, our data indicated that the antitumor effect was CD8 dependent. These results suggested that the development of vaccines encoding VP22 fused to a target antigen might be a promising strategy for improving DNA vaccine potency.
Hung
Chien-Fu
CF
Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
He
Liangmei
L
Juang
Jeremy
J
Lin
Tzyy-Jye
TJ
Ling
Morris
M
Wu
T-C
TC
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D005260:Female; D025922:Mardivirus / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014412:Tumor Virus Infections / Q000517:prevention & control; D019444:Vaccines, DNA / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000956:Antigens, Viral; D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C450446:UL49 protein, Marek's disease virus type 1; D019444:Vaccines, DNA; D014764:Viral Proteins; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; C059731:oncogene protein E7, Human papillomavirus type 16