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Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys

Gene Therapy volume 24, pages 487–492 (2017)Cite this article

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Abstract

The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated in vivo delivery of these antibodies in rhesus monkeys with previous studies that utilized intramuscular delivery with an adeno-associated virus (AAV) vector. Recombinant RRV-4L6 and RRV-5L7 were both shown to stably produce the antibodies in persistently infected B-cell lines in culture. Two RRV-negative rhesus monkeys were experimentally infected with recombinant RRV-4L6 and two with recombinant RRV-5L7. Following infection, the appearance of the delivered antibody was readily detected in all four animals. However, the levels of the delivered antibody were considerably lower than what has been typically observed following intramuscular AAV delivery. Furthermore, three of the four monkeys had an antibody response to the delivered antibody as had been observed previously with intramuscular AAV delivery of these same antibodies. We conclude that this recombinant herpesvirus has no inherent advantage over AAV for delivery of potentially therapeutic monoclonal antibodies in a rhesus monkey model.

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Acknowledgements

This work was supported by funding from the National Institutes of Health (Grant R37 AI063928 to RCD). We thank Wendy Newton and Dr Nancy Schultz-Darken for their assistance with animal protocols and administrative support, Kimberly Weisgrau for technical support and the veterinary staff of the Wisconsin National Primate Research Center. We would also like to thank Dr Shara N Pantry for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, USA

    G F Bischof, Y C Shin, S P Fuchs, J M Martinez-Navio, W A Lauer & R C Desrosiers

  2. Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

    G F Bischof & S P Fuchs

  3. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA

    E G Rakasz

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  1. G F Bischof
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  2. Y C Shin
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  3. S P Fuchs
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  4. J M Martinez-Navio
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  5. W A Lauer
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  6. E G Rakasz
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  7. R C Desrosiers
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Correspondence to R C Desrosiers.

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Bischof, G., Shin, Y., Fuchs, S. et al. Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys. Gene Ther 24, 487–492 (2017). https://doi.org/10.1038/gt.2017.49

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