title: Improved NYVAC-based vaccine vectors.
abstract: While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.
authors.affiliation: The Biodesign Institute at Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Karen V
authors.initials: KV
authors.lastname: Kibler
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Gomez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Perdiguero
authors.forename: Shukmei
authors.initials: S
authors.lastname: Wong
authors.forename: Trung
authors.initials: T
authors.lastname: Huynh
authors.forename: Susan
authors.initials: S
authors.lastname: Holechek
authors.forename: William
authors.initials: W
authors.lastname: Arndt
authors.forename: Victoria
authors.initials: V
authors.lastname: Jimenez
authors.forename: Ruben
authors.initials: R
authors.lastname: Gonzalez-Sanz
authors.forename: Karen
authors.initials: K
authors.lastname: Denzler
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Rafick P
authors.initials: RP
authors.lastname: Sékaly
authors.forename: James
authors.initials: J
authors.lastname: Tartaglia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Jacobs
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005822:Genetic Vectors / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015398:Signal Transduction / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D015699:HIV Envelope Protein gp120; C078787:NYVAC vaccine; D014764:Viral Proteins; D014765:Viral Vaccines; C514793:gp120 protein, Human immunodeficiency virus 1
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