title: Enhancement of sindbis virus self-replicating RNA vaccine potency by linkage of herpes simplex virus type 1 VP22 protein to antigen.
abstract: Recently, self-replicating and self-limiting RNA vaccines (RNA replicons) have emerged as an important form of nucleic acid vaccines. Self-replicating RNA eventually causes lysis of transfected cells and does not raise the concern associated with naked DNA vaccines of integration into the host genome. This is particularly important for development of vaccines targeting proteins that are potentially oncogenic. However, the potency of RNA replicons is significantly limited by their lack of intrinsic ability to spread in vivo. The herpes simplex virus type 1 protein VP22 has demonstrated the remarkable property of intercellular transport and provides the opportunity to enhance RNA replicon vaccine potency. We therefore created a novel fusion of VP22 with a model tumor antigen, human papillomavirus type 16 E7, in a Sindbis virus RNA replicon vector. The linkage of VP22 with E7 resulted in a significant enhancement of E7-specific CD8+ T-cell activities in vaccinated mice and converted a less effective RNA replicon vaccine into one with significant potency against E7-expressing tumors. These results indicate that fusion of VP22 to an antigen gene may greatly enhance the potency of RNA replicon vaccines.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: W F
authors.initials: WF
authors.lastname: Cheng
authors.forename: C H
authors.initials: CH
authors.lastname: Hung
authors.forename: C Y
authors.initials: CY
authors.lastname: Chai
authors.forename: K F
authors.initials: KF
authors.lastname: Hsu
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: M
authors.initials: M
authors.lastname: Ling
authors.forename: T C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D012845:Sindbis Virus / Q000235:genetics*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma; D012324:RNA-Dependent RNA Polymerase