Parenteral inoculation of cotton rats with RSV neutralizing antibodies prior to infection reduces or prevents viral replication in the lungs. This prophylactic effect is dose-dependent and a high concentration of cotton rat serum neutralizing antibodies, i.e., greater than 1:350, is required for prevention of pulmonary infection. This suggested that parenteral administration of RSV antibodies might protect high-risk human infants from RSV infection. Sandoglobulin, a preparation of purified human IgG suitable for intravenous administration, was also highly effective in passive immunoprophylaxis in the cotton rat. Sandoglobulin was also safe and effective for therapy of RSV infection in cotton rats. When ;used therapeutically at the height of RSV infection, Sandoglobulin significantly decreased titer of virus in the lungs. A significant reduction in pulmonary virus titer was observed within three hours of administration of Sandoglobulin, while maximal reduction occurred after 24-48 hours. None of the infected animals treated with Sandoglobulin developed histopathologic lesion, suggesting that Sandoglobulin therapy is unlikely to potentiate RSV disease. A suppressive effect of Sandoglobulin therapy on serum antibody response to infection was observed. Other compartments of the immune system did not appear to be similarly affected because Sandoglobulin-treated cotton rats were immune to rechallenge with RSV, even though some of these animals lacked detectable serum neutralizing antibody at the time of rechallenge. When RSV infected, Sandoglobulin treated cotton rats were reinfected 33 to 42 days later, a normal secondary serum antibody response was observed. This suggests that the immunosuppressive effect of Sandoglobulin is limited to the infection that is treated and that a normal immune response can be anticipated during subsequent infections. Sandoglobulin has also been shown to be highly effective prophylactically and therapeutically in owl monkeys which constitute a permissive primate model for RSV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000345-04
Application #
4688484
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code