Recombinant bovine interferon-alpha(I)1 (rBoIFN-alpha) has known antiv
iral and immunomodulatory effects which have been exploited to reduce
clinical disease in a number of clinical situations including bovine r
espiratory 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 prophylact
ic benefits of rBoIFN-alpha. In this report, we describe a formulation
of rBoIFN-alpha in sesame oil containing calcium stearate which can s
uccessfully sustain the release of rBoIFN-alpha over an 8-day period.
Recombinant bovine IFN-alpha could be measured in serum for 8 days fol
lowing treatment with an initial burst of release 6 h after injection.
After a single subcutaneous depot injection of 50 mg and 100 mg of rB
oIFN-alpha, initial serum levels reached 12-15 ng/ml and 25 ng/ml resp
ectively. 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 te
sted (CD4, CD8, CD2, CD6, B cells, monocytes or MHC class II) were obs
erved, nor were there changes in lymphokine activated killer (LAK), na
tural killer (NK) cell activity, or oxygen radical formation (assessed
by reduction of nitroblue tetrazolium). However, despite the rapid an
d 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 e
quivalent dose of interferon induced a significant rise in 2-5 A synth
etase activity for 4 days only. As 2-5 A synthetase is known to be a c
orrelate of antiviral activity, we propose that this formulation of rB
oIFN-alpha may be one approach to increase the window of protection, l
eading to more effective prevention of bovine respiratory disease.