title: Impact of ETIF deletion on safety and immunogenicity of equine herpesvirus type 1-vectored vaccines.
abstract: Heterologous gene transfer by viral vector systems is often limited by factors such as preexisting immunity, toxicity, low packaging capacity, or weak immunogenic potential. A novel viral vector system derived from equine herpesvirus type 1 (EHV-1) not only overcomes some of these obstacles but also promotes the robust expression of a delivered transgene and the induction of antigen-specific immune responses. Regarding an enhanced safety profile, we assessed the impact of the gene encoding the sole essential tegument protein, ETIF, on the replication and immunogenicity of recombinant EHVs. The deletion of ETIF severely attenuates replication in permissive RK13 cells and a human lung epithelial cell line but without influencing transgene expression. Whereas the intranasal administration of a recombinant luciferase EHV in BALB/c mice resulted in transgene expression in nasal cavities and lungs for 5 to 6 days, the ETIF deletion limited expression to 2 days and resulted in 30-fold-less luminescence. Attenuated replication was accompanied by a decreased capacity to induce CD8(+) T cells against a delivered HIV Gag transgene in BALB/c mice following repeated intranasal application. However, a single subcutaneous immunization with a gag DNA vaccine primed specific T cells for substantial expansion by two subsequent intranasal booster immunizations with either the gag recombinant ETIF mutant or the parental virus. In addition to inducing Gag-specific serum antibodies, this prime-boost strategy clearly outperformed three sequential immunizations with the parental or EHV-ΔETIF virus or repeated DNA vaccination by inducing substantial specific secretory IgA (sIgA) titers.
authors.affiliation: Institute of Medical Microbiology, University of Regensburg, Regensburg, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Hofmann-Sieber
authors.forename: Jens
authors.initials: J
authors.lastname: Wild
authors.forename: Nicole
authors.initials: N
authors.lastname: Fiedler
authors.forename: Karsten
authors.initials: K
authors.lastname: Tischer
authors.forename: Jens
authors.initials: J
authors.lastname: von Einem
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Osterrieder
authors.forename: Heike
authors.initials: H
authors.lastname: Hofmann
authors.forename: Josef
authors.initials: J
authors.lastname: Köstler
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
mesh_terms: D000818:Animals; D002460:Cell Line; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D017353:Gene Deletion; D005822:Genetic Vectors / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D004861:Herpesvirus 1, Equid / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D014612:Vaccines / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics* / Q000276:immunology; D014779:Virus Replication
chemical_list: D014612:Vaccines; D015678:Viral Structural Proteins
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