Immunoglobulin administration and ribavirin therapy: efficacy in respiratory syncytial virus infection of the cotton rat.

Abstract

We studied the effects of combined administration of human immunoglobulin (IVIG) and ribavirin aerosol on respiratory syncytial virus (RSV) infection in cotton rats (Sigmodon hispidus). Cotton rats assigned to receive combined therapy were administered Gamimune, a preparation of purified IVIG with a high titer of anti-RSV neutralizing activity, intraperitoneally 24 h prior to intranasal RSV challenge and then treated with ribavirin aerosol 3 days after challenge. Lung viral titers from these cotton rats (geometric mean titers [GMT] log10 = 0.15 +/- 0.5) were lower than titers from untreated animals (GMT, log10 = 3.7 +/- 0.6) and animals treated with either IVIG alone (GMT, log10 = 1.8 +/- 0.9) or ribavirin alone (GMT, log10 = 1.9 +/- 1.1). Only one of 12 cotton rats treated with both IVIG and ribavirin had a demonstrable titer of virus after RSV challenge. When IVIG administration was delayed until day 3 after virus challenge, lung viral titers were still lowest in animals receiving both IVIG and ribavirin. In comparison, there was no additive antiviral effect between IVIG and ribavirin against RSV infections of HEp-2 cells in vitro. Pathologic changes on histologic examination of pulmonary tissues from animals challenged with RSV were least prominent in animals treated with both IVIG and ribavirin. Despite the apparent absence of in vitro additive antiviral effect, combined use of IVIG and ribavirin was more efficacious against RSV infection in the cotton rat than use of either agent alone.