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Infections

Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus

Bone Marrow Transplantation volume 51, pages 119–126 (2016)Cite this article

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Abstract

Respiratory syncytial virus (RSV) is a significant cause of bronchiolitis and pneumonia in several high health risk populations, including infants, elderly and immunocompromised individuals. Mortality in hematopoietic stem cell transplant recipients with lower respiratory tract RSV infection can exceed 80%. It has been shown that RSV replication in immunosuppressed individuals is significantly prolonged, but the contribution of pulmonary damage, if any, to the pathogenesis of RSV disease in this susceptible population is not known. In this work, we tested RI-002, a novel standardized Ig formulation containing a high level of RSV-neutralizing Ab, for its ability to control RSV infection in immunocompromised cotton rats Sigmodon hispidus. Animals immunosuppressed by repeat cyclophosphamide injections were infected with RSV and treated with RI-002. Prolonged RSV replication, characteristic of immunosuppressed cotton rats, was inhibited by RI-002 administration. Ab treatment reduced detection of systemic dissemination of viral RNA. Importantly, pulmonary interstitial inflammation and epithelial hyperplasia that were significantly elevated in immunosuppressed animals were reduced by RI-002 administration. These results indicate the potential of RI-002 to improve outcome of RSV infection in immunocompromised subjects not only by controlling viral replication, but also by reducing damage to lung parenchyma and epithelial airway lining, but further studies are needed.

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Acknowledgements

We thank Hannah Sanford-Crane, Lauren Hippler, Julio Canas, Charles Smith and Martha Malache for help with the animal studies. We also thank Tom March for help with evaluating pulmonary histopathology and Maryanne Formica for technical assistance with the neutralizing assays.

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Authors and Affiliations

  1. Department of Molecular Biology/Virology, Sigmovir Biosystems, Inc., Rockville, MD, USA

    M Boukhvalova & J C G Blanco

  2. Infectious Diseases Unit, Rochester General Hospital, University of Rochester Medical Center, Rochester, NY, USA

    A R Falsey

  3. ADMA Biologics, Ramsey, NJ, USA

    J Mond

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  1. M Boukhvalova
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  2. J C G Blanco
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Correspondence to M Boukhvalova.

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Competing interests

Sigmovir Biosystems was funded by ADMA to test RI-002 in the cotton rat model.

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Boukhvalova, M., Blanco, J., Falsey, A. et al. Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus. Bone Marrow Transplant 51, 119–126 (2016). https://doi.org/10.1038/bmt.2015.212

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