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Clinical and Vaccine Immunology, November 2006, p. 1246-1254, Vol. 13, No. 11
1071-412X/06/$08.00+0     doi:10.1128/CVI.00200-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Recombinant Bovine Herpesvirus 4 (BoHV-4) Expressing Glycoprotein D of BoHV-1 Is Immunogenic and Elicits Serum-Neutralizing Antibodies against BoHV-1 in a Rabbit Model{triangledown}

Gaetano Donofrio,1* Sandro Cavirani,1 Alain Vanderplasschen,2 Laurent Gillet,2 and Cesidio Filippo Flammini1

Università di Parma, Facoltà di Medicina Veterinaria, Dipartimento di Salute Animale, Sezione di Malattie Infettive degli Animali, via del Taglio 8, 43100 Parma, Italy,1 Immunology-Vaccinology, B43 b Faculty of Veterinary Medicine, Boulevard de Colonster 20, University of Liège, B-4000 Liège, Belgium2

Received 29 May 2006/ Returned for modification 30 July 2006/ Accepted 4 August 2006

Several biological characteristics of bovine herpesvirus 4 (BoHV-4) make it a good candidate as a gene delivery vector for vaccination purposes. These characteristics include little or no pathogenicity, unlikely oncogenicity, the capability to accommodate large amounts of foreign genetic material, the ability to infect several cell types coming from different animal species, and the ability to maintain transgene expression in both undifferentiated and differentiated cells. Starting from BoHV-4 cloned as a bacterial artificial chromosome (BAC), we used MuA transposase-mediated in vitro transposition to generate recombinant BoHV-4 expressing the immunodominant glycoprotein D (gD) of BoHV-1, one of the most important pathogens of cattle. Although a cis-acting element from woodchuck hepatitis virus (the woodchuck hepatitis virus posttranscriptional regulatory element [WPRE]) in the 3' end of the gD expression cassette was required for maximal gD expression from plasmids in transient transfection assays, this element was not necessary for efficient expression of gD from recombinant BoHV-4 genomes. BoHV-4 recombinants containing gD expression cassettes with or without the WPRE expressed gD at similarly high levels. Several cell lines originating from different animal species expressed gD when infected with BoHV-4 recombinants. When rabbits were immunized with one of the recombinants, high levels of serum neutralizing antibodies against BoHV-1 were generated. This work is one of the first demonstrations of the use BoHV-4 as a vector for vaccine purposes and may provide the basis for BoHV-1 vaccination of cattle with recombinant BoHV-4.

* Corresponding author. Mailing address: Dipartimento di Salute Animale, Sezione di Malattie Infettive, Facoltà di Medicina Veterinaria, via del Taglio 8, 43100 Parma, Italy. Phone: 00390521902677. Fax: 00390521902672. E-mail: gaetano.donofrio{at}unipr.it.

{triangledown} Published ahead of print on 23 August 2006.

Clinical and Vaccine Immunology, November 2006, p. 1246-1254, Vol. 13, No. 11
1071-412X/06/$08.00+0     doi:10.1128/CVI.00200-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Donofrio, G., Franceschi, V., Capocefalo, A., Taddei, S., Sartori, C., Bonomini, S., Cavirani, S., Cabassi, C. S., Flammini, C. F. (2009). Cellular Targeting of Engineered Heterologous Antigens Is a Determinant Factor for Bovine Herpesvirus 4-Based Vaccine Vector Development. CVI 16: 1675-1686 [Abstract] [Full Text]  


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