A slow release formulation for recombinant bovine interferon alpha I-1.
Recombinant bovine interferon-alpha I1 (rBoIFN-alpha) has known antiviral and immunomodulatory effects which have been exploited to reduce clinical disease in a number of clinical situations including bovine respiratory diseases. A slow release rBoIFN-alpha formulation may be of value to reduce bovine respiratory disease under field conditions by extending the period of protection, and hence improving the prophylactic benefits of rBoIFN-alpha. In this report, we describe a formulation of rBoIFN-alpha in sesame oil containing calcium stearate which can successfully sustain the release of rBoIFN-alpha over an 8-day period. Recombinant bovine IFN-alpha could be measured in serum for 8 days following treatment with an initial burst of release 6 h after injection. After a single subcutaneous depot injection of 50 mg and 100 mg of rBoIFN-alpha, initial serum levels reached 12-15 ng/ml and 25 ng/ml respectively. Correlating with this burst of release, there was a decrease in the number of circulating CD4-CD8- gamma delta+ T lymphocytes, and a slight neutropenia. No alterations in other cell phenotypes tested (CD4, CD8, CD2, CD6, B cells, monocytes or MHC class II) were observed, nor were there changes in lymphokine activated killer (LAK), natural killer (NK) cell activity, or oxygen radical formation (assessed by reduction of nitroblue tetrazolium). However, despite the rapid and short-lived burst of rBoIFN-alpha, levels of 2-5 oligoadenylate (2-5 A) synthetase remained elevated for 8 days. The sustained increase of 2-5 A synthetase was not due to the high initial dose released during the burst 6-12 h after injection, since injection of a bioavailable equivalent dose of interferon induced a significant rise in 2-5 A synthetase activity for 4 days only. As 2-5 A synthetase is known to be a correlate of antiviral activity, we propose that this formulation of rBoIFN-alpha may be one approach to increase the window of protection, leading to more effective prevention of bovine respiratory disease.
Hughes
H P
HP
Veterinary Infectious Disease Organization, Saskatoon, Canada.
Rossow
S
S
Campos
M
M
Rossi-Campos
A
A
Janssen
S
S
Godson
D L
DL
Daflon
B
B
Voirol
M J
MJ
Gerber
C
C
Babiuk
L A
LA
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood*; D000818:Animals; D002417:Cattle; D003692:Delayed-Action Preparations; D007370:Interferon Type I / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007958:Leukocyte Count; D009503:Neutropenia / Q000139:chemically induced; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors
D003692:Delayed-Action Preparations; D007370:Interferon Type I; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase