title: Vaccination with synthetic constructs expressing cytomegalovirus immunogens is highly T cell immunogenic in mice.
abstract: There is no licensed vaccine or cure for human cytomegalovirus (CMV), a ubiquitous β-herpesvirus infecting 60-95% of adults worldwide. Infection can cause congenital abnormalities, result in severe disease in immunocompromised patients, and is a major impediment during successful organ transplantation. In addition, it has been associated with numerous inflammatory diseases and cancers, as well as being implicated in the development of essential hypertension, a major risk factor for heart disease. To date, limited data regarding the identification of immunogenic viral targets has frustrated CMV vaccine development. Based upon promising clinical data suggesting an important role for T cells in protecting against disease in the transplantation setting, we designed a novel panel of highly-optimized synthetic vaccines encoding major CMV proteins and evaluated their immune potential in murine studies. Vaccination induced robust CD8+ and CD4+ T cells of great epitopic breadth as extensively analyzed using a novel modified T cell assay described herein. Together with improved levels of CMV-specific T cells as driven by a vaccine, further immune evaluation of each target is warranted. The present model provides an important tool for guiding future immunization strategies against CMV.
authors.affiliation: Department of Pathology and Laboratory Medicine; University of Pennsylvania, PA, USA.
authors.forename: Devon J
authors.initials: DJ
authors.lastname: Shedlock
authors.forename: Kendra T
authors.initials: KT
authors.lastname: Talbott
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Wu
authors.forename: Christine M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Karuppiah
authors.initials: K
authors.lastname: Muthumani
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: Sita
authors.initials: S
authors.lastname: Awasthi
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D018274:Electroporation; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D022482:Cytomegalovirus Vaccines; D014614:Vaccines, Synthetic