Summary:Respiratory syncytial virus (RSV) has emerged as a leading cause of pneumonia, with high mortality, in bone marrow transplant (BMT) recipients, as well as in other profoundly immunocompromised patients, such as myelosuppressed adults with leukemia. We tested the efficacy of immunoglobulin with high anti-RSV neutralizing antibody levels (RSVIG) for prophylaxis and therapy of RSV infection in cotton rats undergoing prolonged immunosuppression with cyclophosphamide. These animals experience persistent infection, a model which is similar to the disease seen in post-BMT humans. Both prophylaxis and therapy reduced pulmonary viral replication over 500-fold to nearly undetectable levels. In animals receiving continual immunosuppression, the use of multiple therapeutic doses of RSVIG was able to prevent rebound viral replication, though virus was not completely eliminated. Keywords: RSV; BMT; immunotherapy; RSVIG; cyclophosphamide; cotton rat Advances in bone marrow transplantation (BMT) have led to a large increase in the number of procedures done, partially due to increasingly aggressive attempts to cure patients of several types of malignancy as well as a variety of other systemic diseases. However, gains due to improvements in BMT are still offset by high rates of morbidity and mortality due to infectious diseases in the immediate post-transplant period. A variety of methods have been effective in reducing rates of some early opportunistic infections, such as cytomegalovirus and Pneumocystis carinii. 1 In contrast, respiratory syncytial virus (RSV), a ubiquitous respiratory virus considered by many to be a significant pathogen only during infancy, has emerged as a major cause of morbidity and mortality in BMT recipients of all ages. 2 Attempts to treat this infection with the antiviral agent ribavirin have been largely unsuccessful, and BMT patients who develop RSV pneumonia have extremely high rates of mortality. [3][4][5][6] IVIG with high anti-RSV activity (RSVIG) is effective Materials and methods AnimalsWeanling inbred cotton rats (Sigmodon hispidus) were obtained from Virion Systems Inc. Animals were housed in large polycarbonate cages in small groups, and were provided water and rat chow ad libitum. ImmunosuppressionAnimals were treated with intraperitoneal (i.p.) injections of cyclophosphamide (CY) at a dose of 50 mg/kg three times weekly for at least 21 days prior to viral challenge. Immunosuppressive therapy was continued until the end of each experiment. To monitor the level of immunosuppression during these experiments, selected suppressed and control animals were bled for complete blood count (CBC) and white blood cell differential counts at the time of viral challenge. Nasal and pulmonary virus titers were determined at several intervals post viral challenge. VirusThe long strain of RSV (Group A), obtained from the American Type Culture Collection, was used as the challenge virus. A single pool propagated in HEp-2 cells containing 1 × 10 6 plaque forming units (p.f.u.) per ml was used for all ...