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Journal of Virology, September 2003, p. 9312-9323, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9312-9323.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Novel Recombinant Parapoxvirus Vectors Induce Protective Humoral and Cellular Immunity against Lethal Herpesvirus Challenge Infection in Mice

Timo Fischer, Oliver Planz, Lothar Stitz, and Hanns-Joachim Rziha*

Federal Research Centre for Virus Diseases of Animals, Institute of Immunology, D-72076 Tuebingen, Germany

Received 4 April 2003/ Accepted 10 June 2003

Orf virus (ORFV; Parapoxvirus ovis) was used to develop a novel vector system for the generation of effective and safe live vaccines. Based on the attenuated ORFV strain D1701-V, recombinants were produced that express the glycoproteins gC (D1701-VrVgC) or gD (D1701-VrVgD) of the alphaherpesvirus of swine, pseudorabies virus (PRV). Expression of gC and gD was also demonstrated on the surface of recombinant virus-infected murine cells that do not produce infectious ORFV. Single or combined immunization with the ORFV recombinants protected different mouse strains of a host species nonpermissive for ORFV against a fulminant, lethal PRV challenge infection equal to immunization with PRV live vaccine. Most notably, even a single immunization with D1701-VrVgC was protective, whereas two applications of D1701-VrVgD were required for immune protection. The higher protective capacity of D1701-VrVgC correlated with the induction of a strong specific humoral immune response. This suggestion was supported by transfer experiments using sera from recombinant-immunized mice, which resulted in partial gC but not gD antibody-mediated protection of the naïve recipients. Remarkably, immunization of different immune-deficient mice demonstrated that the application of the PRV gC-expressing recombinant controlled the challenge infection in the absence of either CD4+ or CD8+ T cells, B cells, or an intact perforin pathway. In contrast, D1701-VrVgD-immunized mice lacking CD4+ T cells exhibited reduced protection, whereas animals lacking CD8+ T cells, B cells, or perforin resisted the challenge infection. The present study demonstrates the potential of these new vector vaccines to efficiently prime both protective humoral and cell-mediated immune mechanisms in a host species nonpermissive for the vector virus.

* Corresponding author. Mailing address: Federal Research Centre for Virus Diseases of Animals, Institute of Immunology, Paul-Ehrlich-Str. 28, D-72076 Tuebingen, Germany. Phone: (49) 7071-967 253. Fax: (49) 7071-967 253. E-mail: achim.rziha{at}tue.bfav.de.

Journal of Virology, September 2003, p. 9312-9323, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9312-9323.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hausmann, J., Baur, K., Engelhardt, K. R., Fischer, T., Rziha, H.-J., Staeheli, P. (2005). Vaccine-induced protection against Borna disease in wild-type and perforin-deficient mice. J. Gen. Virol. 86: 399-403 [Abstract] [Full Text]  
  • Henkel, M., Planz, O., Fischer, T., Stitz, L., Rziha, H.-J. (2005). Prevention of Virus Persistence and Protection against Immunopathology after Borna Disease Virus Infection of the Brain by a Novel Orf Virus Recombinant. J. Virol. 79: 314-325 [Abstract] [Full Text]  
  • Spehner, D., De Carlo, S., Drillien, R., Weiland, F., Mildner, K., Hanau, D., Rziha, H.-J. (2004). Appearance of the Bona Fide Spiral Tubule of Orf Virus Is Dependent on an Intact 10-Kilodalton Viral Protein. J. Virol. 78: 8085-8093 [Abstract] [Full Text]  


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