Enhanced therapeutic efficacy of poly(ICLC) and ribavirin combinations against Rift Valley fever virus infection in mice.
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.
Kende
M
M
Department of Antiviral Studies, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701-5011.
Lupton
H W
HW
Rill
W L
WL
Levy
H B
HB
Canonico
P G
PG
D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000627:therapeutic use* / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D007369:Interferon Inducers / Q000008:administration & dosage / Q000627:therapeutic use*; D008747:Methylcellulose / Q000031:analogs & derivatives*; D051379:Mice; D011070:Poly I-C / Q000008:administration & dosage / Q000627:therapeutic use*; D011107:Polylysine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000031:analogs & derivatives; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D012263:Ribonucleosides / Q000627:therapeutic use*; D012295:Rift Valley Fever / Q000188:drug therapy*
D007369:Interferon Inducers; D012263:Ribonucleosides; D011107:Polylysine; D012254:Ribavirin; C019531:poly ICLC; D008747:Methylcellulose; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C