Enhanced therapeutic efficacy of poly(ICLC) and ribavirin combinations against Rift Valley fever virus infection in mice

Abstract

The therapeutic efficacy of polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine and carboxymethyl cellulose [poly(ICLC)] given alone or in combination with ribavirin was evaluated in Swiss Webster mice infected with Rift Valley fever virus. Four or more 20-micrograms doses of poly(ICLC) given at various intervals beginning 24 h after infection protected all mice against death. On the other hand, a treatment regimen consisting of only three doses of poly(ICLC) given 24 h postinfection resulted in a 50% survival rate. When initiated 48 h postinfection, an extended treatment regimen with the same dose was required to yield 40% survivors. Lower doses (5 micrograms) of poly(ICLC) per mouse were only marginally effective even when six injections were given between days 1 and 9 postinfection. The combined administration of ribavirin and poly(ICLC) initiated as late as 48 h postinfection was effective even when treatment consisted of doses that were ineffective when either drug was used alone.