Efficacy of aerosolized recombinant interferons against vesicular stomatitis virus-induced lung infection in cotton rats.

Cotton rats (Sigmodon hispidus) were inoculated intranasally with vesicular stomatitis virus (VSV) and exposed to different regimens of small particle aerosols of either recombinant human alpha interferon A (rIFN-alpha A) or hybrid recombinant human alpha interferon A/D (rIFN-alpha A/D). Preliminary in vitro tests indicated that both recombinant IFNs were effective in protecting primary cotton rat pulmonary cells against VSV replication. However, rIFN-alpha A/D was 20-fold more active than rIFN-alpha A in these tests. In the in vivo tests, in contrast to control animals inoculated with VSV, but not treated, or treated only with aerosols of saline, animals exposed to either rIFN-alpha A or -alpha A/D for 8 h per day before and/or following VSV inoculation had no detectable virus titers in their lungs. In experiments in which groups of animals were treated for shorter periods, rIFN-alpha A was less effective than rIFN-alpha A/D in suppressing replication of VSV in lungs of these animals.