title: Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus.
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.
authors.affiliation: Department of Molecular Biology/Virology, Sigmovir Biosystems, Inc., Rockville, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Boukhvalova
authors.affiliation: Department of Molecular Biology/Virology, Sigmovir Biosystems, Inc., Rockville, MD, USA.
authors.forename: J C G
authors.initials: JC
authors.lastname: Blanco
authors.affiliation: Infectious Diseases Unit, Rochester General Hospital, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Falsey
authors.affiliation: ADMA Biologics, Ramsey, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mond
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology*; D001988:Bronchiolitis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D016867:Immunocompromised Host; D011024:Pneumonia, Viral / Q000188:drug therapy* / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000502:physiology; D016205:Sigmodontinae; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000914:Antibodies, Viral