Inhalation efficacy of RFI-641 in an African green monkey model of RSV infection.
Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73-1.34 PFU/ml (P-value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection.
Weiss
W J
WJ
Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. weissw@wyeth.com
Murphy
T
T
Lynch
M E
ME
Frye
J
J
Buklan
A
A
Gray
B
B
Lenoy
E
E
Mitelman
S
S
O'Connell
J
J
Quartuccio
S
S
Huntley
C
C
D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D002522:Chlorocebus aethiops / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D015394:Molecular Structure; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014227:Triazines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D000336:Aerosols; C434804:RFI 641; D013449:Sulfonamides; D014227:Triazines