Publikationsdatenbank

Impact of ETIF deletion on safety and immunogenicity of equine herpesvirus type 1-vectored vaccines (2010)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Hofmann-Sieber, Helga

Wild, Jens

Fiedler, Nicole

Tischer, Karsten

von Einem, Jens

Osterrieder, Nikolaus

Hofmann, Heike

Köstler, Josef

Wagner, Ralf

Quelle

Journal of virology : publ. by the American Society for Microbiology

Bandzählung: 84

Heftzählung: 22

Seiten: 11602 – 11613

ISSN: 1098-5514

Sprache

Englisch

Verweise

DOI: 10.1128/JVI.00677-10

Pubmed: 20826695

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.