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Journal of Virology, May 2005, p. 5445-5454, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5445-5454.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Potential of Equine Herpesvirus 1 as a Vector for Immunization

Sascha Trapp,1,2 Jens von Einem,1,2 Helga Hofmann,3 Josef Köstler,3 Jens Wild,3 Ralf Wagner,3 Martin Beer,2 and Nikolaus Osterrieder1,2*

Department of Microbiology and Immunology, Veterinary College, Cornell University, Ithaca, New York 14853,1 Friedrich-Loeffler-Institute, D-17493 Greifswald-Insel Riems, Germany,2 Institut für Mikrobiologie und Hygiene, Universität Regensburg, Franz-Josef-Strauß-Allee 11, D-93053 Regensburg, Germany3

Received 9 December 2004/ Accepted 15 December 2004

Key problems using viral vectors for vaccination and gene therapy are antivector immunity, low transduction efficiencies, acute toxicity, and limited capacity to package foreign genetic information. It could be demonstrated that animal and human cells were efficiently transduced with equine herpesvirus 1 (EHV-1) reconstituted from viral DNA maintained and manipulated in Escherichia coli. Between 13 and 23% of primary human CD3+, CD4+, CD8+, CD11b+, and CD19+ cells and more than 70% of CD4+ MT4 cells or various human tumor cell lines (MeWo, Huh7, HeLa, 293T, or H1299) could be transduced with one infectious unit of EHV-1 per cell. After intranasal instillation of EHV-1 into mice, efficient transgene expression in lungs was detectable. Successful immunization using EHV-1 was shown after delivery of the human immunodeficiency virus type 1 Pr55gag precursor by the induction of a Gag-specific CD8+ immune response in mice. Because EHV-1 was not neutralized by human sera containing high titers of antibodies directed against human herpesviruses 1 to 5, it is concluded that this animal herpesvirus has enormous potential as a vaccine vector, because it is able to efficiently transduce a variety of animal and human cells, has high DNA packaging capacity, and can conveniently be maintained and manipulated in prokaryotic cells.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. Phone: (607) 253-4045. Fax: (607) 253-3384. E-mail: no34{at}cornell.edu.

Journal of Virology, May 2005, p. 5445-5454, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5445-5454.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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