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Journal of Virology, July 2003, p. 7830-7842, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7830-7842.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Application of Chimeric Feline Foamy Virus-Based Retroviral Vectors for the Induction of Antiviral Immunity in Cats {dagger}

Astrid Schwantes,1,{ddagger} Uwe Truyen,2,3 Joachim Weikel,3 Christian Weiss,4 and Martin Löchelt1*

Abteilung Retrovirale Genexpression, Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg,1 Institut für Tierhygiene und Öffentliches Veterinärwesen, Veterinärmedizinische Fakultät, Universität Leipzig, Leipzig,2 Zentralinstitut, Tiergesundheitsdienst Bayern e.V., Poing,3 Bayer AG, Monheim, Germany4

Received 29 January 2003/ Accepted 30 April 2003

In order to define the potential and applicability of replication-competent foamy virus-based vaccine vectors, recombinant feline foamy virus (FFV) vectors encoding defined segments of the feline calicivirus (FCV) capsid protein E domain were constructed. In cell cultures, these FFV-FCV vectors efficiently transduced and expressed a hybrid fusion protein consisting of the essential FFV Bet protein and the attached FCV E domains. The stability of the vectors in vitro was inversely correlated to the size of the heterologous insert. The deletion of a part of the FFV U3 sequence in these FFV-FCV vectors did not interfere with replication and titer in cell cultures but increased the genetic stability of the hybrid vectors. Selected chimeric vectors were injected into immunocompetent cats and persisted in the transduced host concomitant with a strong and specific humoral immune response against vector components. In a substantial number of cats, antibodies directed against the FCV E domain were induced by the FFV-FCV vectors, but no FCV-neutralizing activities were detectable in vitro. When the vaccinated cats were challenged with a high-titer FCV dose, sterile immunity was not induced by any of the hybrid FFV-FCV vectors. However, the FFV-FCV vector with a truncated U3 region of the long terminal repeat promoter significantly reduced the duration of FCV shedding after challenge and suppressed the appearance of FCV-specific ulcers. Possible mechanisms contributing to the partial protection will be discussed.


* Corresponding author. Mailing address: Abteilung Retrovirale Genexpression, Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69009 Heidelberg, Germany. Phone: 49-6221-424853. Fax: 49-6221-424865. E-mail: m.loechelt{at}dkfz-heidelberg.de.

{dagger} We dedicate this paper to Harald zur Hausen for his continuous support on the occasion of his retirement as the Chair of the Deutsches Krebsforschungszentrum.

{ddagger} Present address: Paul-Ehrlich-Institut, Abteilung Medizinische Biotechnologie, Langen, Germany.


Journal of Virology, July 2003, p. 7830-7842, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7830-7842.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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