CA1329122C - Prevention of bovine respiratory disease complex in cattle by administration of interferon - Google Patents

Abstract

PREVENTION OF BOVINE RESPIRATORY DISEASE COMPLEX IN CATTLE BY
ADMINISTRATION OF INTERFERON
Abstract of the disclosure This invention is directed to the field of animal health and, more particularly, to reducing the incidence of bovine respiratory disease complex.

For the purposes of the present invention this and other objects surprisingly have been met by providing a method for reducing the incidence and severity of bovine respiratory disease complex comprising administering systemically a prophylactically effective amount of bovine interferon to young cattle before infection by an infectious disease-causing virus or microorganism causes an outbreak of the clinical disease.

Description

- 1 ~329 ~22 5-16215/+/CGC 1241 PREVENTION OF BOVINE RESPIRATORY DISEASE COMPLEX IN CATTLE BY
ADMI~ISTRATION OF INTERFERON

Field of the invention This invention i9 directed to the field of anlmal health and, more particularly, to reducing the incidence of bovine respiratory disease complex.

Back~round of the invention Several form~ of respiratory diseases in cattle, commonly referred to as I'Bovine Respiratory Disease Complex (BRD)" are known.

Bovine respiratory disease complex i9 a principal cause of 109~ in the cattle industry.

One form of BRD, the so-called "Shipping Fever" preferably occurs in newly weaned calve~, generally within the Eirst week after th~y are moved to feedlots, where they are exposed to stress as a resuilt of handling~ transportation or bad weather.

"Shipping Fever" s the most prevaleDt and economically significant diseases affecting the Noreh American cattle industry with losses ranging between a quarter to ono billion dollar~ annually.

~nother form of "BRD" is "Enzootic Calf PneumDnia", an outbreak of pneumonia that particularly-affects calves housed in stables, generally in the first few months of life.

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2 ~L329~22 Some calves in a group develop acute respiratory disease and die.
Other calves usually develop a milder disease 3 which iæ associated with irritation of the mucous membranes of the nose and eyes and with nasal and ocular d~scharge.
These calves may progress to the more acute form, or may recover.
Those that recover, however, risk sufferin~ a relapse within a few weeks.

While "BRD" is most common in beef cattle, it also occurs in dairy cattle. All ages are susceptible, but the disaase most commonly occurs in newly purchased young cattle that have recently been introduced into a herd. As a result, the introduction of new dairy stock into a herd will be follow0d by an outbreak of pneumonia in the herd.

"Bovine Respiratory Disease Complex" is believed to be caused by a combination of factors, such as damage to the respiratory tract and stress. Damage to the respiratory tract may be caused by viruses, such as a bovine herpesvirus, or different mycoplasma and/or chlamydia strains. Stress may be caused by, for example, weaning9 castration, overcrowding, temperature changes and secondary infection by bacteria, such as pasteurella, Viruses challenge and stress may combine to cause immunosuppression of cattle. This im~unosuppression may in turn lead to secondary colonization of the lungs with bacteria principally Pasteurella haemolytica (sse Joseph M. Cummlngs, "Feedlot Diseases and Parasites" in The Feedlot, G.B. Thompson and Clayton C. O'Mary, ed., Lea and Febiger Philadelphis, Third Ed.; 1983~.

Predisposing factors, therefore, are of ma~or importance in susceptibility to "Shipping Fever" or "Enzootic Calf Pneumonia".
Among the most prevalent factors are physical stresses, chemical agents and psychological factors.
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3 ~329~22 Physical stresses include weaning, temperature extremes and rapld changes in tha weathsr, hum~dity, irregular feeding and watering, changes in ration, dust, overcrowding, mixing and confining of the calves.

The stre~s felt by~recently arrived calves due to such factors is considered to be a ma~or factor contributing to pneumonia. In addition calves are often vaccinated, dehorned, castrated, implanted and injected with vitamins and antiblotics within a few days after arrival. These procedures are also performed on cattle that are exhausted after a long truck ride under crowding conditions.

Chemical agents that cause stress include amonia fumes and toxic gases generated during agricultural operations.

Concomltant diseases such as para3ite attack have also been demonstrated to have an adverse effect on the abillty to reslst infection.

All these factors induce pathological changes such as depression of the immune system (for example endogenous steroid release with resulting impairment of neutrophil and lymphocyt function) or paralysis of or inhibition of mucine secretion in the respiratory tract.

Among the maJor vlruses implicated in "BRD" are bovine herpes viru~
type I (BHV-l or infectious rhinotracheitis virus), parainfluenza type 3 (PI-3), bovine viral diarrhea virus (BYD) and bovine respiratory syncltial virus (BRSY).

Viruses may cause immunosuppression by several mechanis~s: they may, for exampleS lyse or functionally impalr lymphocyte functions or lower the activity of the body's own bactericidal mechanism3 especially those involving macrophages and neutrophils, which are important in clearing gram-negative bacteria from the lungs.

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132~1122 In addltion, viruses alter the ability of macrophages to ingest antibody coated bactaria (decreased Fc receptor activity). ~ven if the bacteria are ingested they are not killed aR efficiently by virus infected macrophages. Furthermore it has been shown that viral infection can reduce chemotactic factor production by alveolar macrophages and therefore dramat~cally influence neutrophll recruitment into the lung.

Virus infection may also alter neutrophil mobility and induce neutrophil dysfunction.

Finally, if the alveolar mscrophages sxpress viral antigen on their surface, either due to replication or phagocytosis of the viruses, the cytotoxic T cells could be directed against these cells and further impalr their functions.

As seen earlier, viral infectlon and stress appear to enhance adherence and colonization of the respiratory tract by both gram positive and gram negative bacteria.

Although there are a variety of bacteria that can colonize the lung and cause bacterial pneumonia, the majority of bovine pneumonias are cau6ed by Pasteurella haemolytica A-I.

In addition to P. haemolytica, P. multocida, and ~aemophilus somnus are al80 commonly isolated from the respiratory tract of animals suffering from "BRD", as are various Mycoplasma species (N. b~vi~ QE and M. bovirh1nis).

After rapid growth of P. hae~olytlca in the nasopharynx the bacteria canj for example, enter the lung inside droplets.

Furthermore P. haemolytica produces a soluble cytotoxin (leukotox~n) that can directly impair the function or cause the death of ruminant leukocytes.

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,': , , ~ ~L329122 -- 5 --After phagocytlzing the bacteria, alveolar macrophages and neutrophils may be damaged or die. Dead neutrophils in the lungs contribute to the lesions caused by pneumonia.

"BRD" usually occurs in cattle 3 to 15 days after they have beeD
stressed.

Affected calves usually appear depressed and are without appetite. A
~ucopurulent nasal dlscharge and a quiet cough are common. The respiratory rate is increased from a normal of 30 per minute up to 80 to 100 per minute. Affected calves have also a fever ranging from 40 to 41,5C.

Fxaminatlon o~ the lungs with a ststho~cope will usually reveal evidence of bronchopneumonia or even of pleurisy.

Pasteurella haemolytica produces severe lung leslons. Flbrin deposition and capillary thro~bosis are the two main pathological features of pasteurellosis.

For the cattle industry the losses caused by "BRD" are the results not only of the death of animals, but also of the costs of treat-ment, weight loss, inefficient feed utilisation, extra labor, condemnations and poor performers, all of which result from the disease.

Therefore, while looking for po sibilities for an adequate treatment of "BRD", suggestion~ have been made to reduce ths incidence and severity of respiratory diseases in cattle by admini~tering interferons.

The interferons (IFN) are a family of proteins classified into three type3, alpha, beta and gamma. The classification is based upon antigenic ~peciflcl~y, g~ne organisation, structure, p~ sensitivity9 cellular origin and biological activity of the interferon proteins.

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- 6 - ~ 32 9 ~2 2 The different types of interferons may be derived from animals such as cattle, pigs and humans.

The suggestions to treat cattle with interferons in order to reduce the incidence and severity of respiratory disease have been supported by model studies. In one model study, cattle were infected with herpesvirus ~BHV-l)o The administration of human interferon wa~ shown to reduce the severity of the infection. See Roney et al., Am.J.Vet.Res. 46, 1251-1255 (1985).

Model studies are flawed, however, in that they do not subject the cattle to the combination of stresses and varieties of different viruses and microorganisms that cattle are subjected to under actual field condltions as they move through a salebarn, feedlot and stockyard.

Successful model studies do not, therefore, necessarily mean that the tre~tment of cattle with bovine lnterferon under actual field co~ditions will be effective against infectious respiratory diseases. Nor do such studles provide the optimal conditions ior interferon inoculation in order to reduce the incidence and severity of infectious diseases under actual field conditions.

Questions such as the best time and method of inoculation remain.

It is, accordingly, an ob~ect of the present invention to provide a method for reducing the incidence and severity of bovine respiratory disease complex under actual field conditions by prophylactic administration of interPeron to cattle.

This and other ob~ects as will be apparent from the ~ollowing de~cription of the invention surprisingly have been met by providing a method for reduci~g the incidence and ~everity of bovine respiratory disease complex comprising administering systemically a .

1329~2 propbylactically effective amount of bovine interferon to young cattle before infectlon by an infectious disease-causing virus or microorganlsm causes an outbseak of the clinical dlsease.

Description of the invention The intPrferon useful in the present invention ~ay be alpha, beta or gamma interferon derived from cattle. The interferon may be isolated from the cattle and purified, or it may be produced by recombinant DNA technology.

All three types of IFN can play a direct role in controlling virus replication within susceptible cells and are involved in the regulation of the immune function. A11 IFNs can stimulate or enhance the ~irst line of immune defense-phagocytosi~ and cell killing.

Alpha type interferons are sscreted by lymphocytes and other leukocytes in response to viral infections.

The cloning and expression of DNA encoding bovine interferons has showD that the bovine genome contains two distlnct classes of IFN-genes, namely the BoIFN-~I and BoIFN-aII gene clas~es. These classes consist of 10-12 and 15-20 subtypes, respectively. The gene coding for BoI~N-~I1, one subtype of the BoIFN-aI family, has been cloned and expressed in bacterial cells in nrder to evaluate its activities in vitro and in vivo.

Recombinant bovine lnterferon alphaI (rBoIFN-~ , trademark I Interceptor~, is a basic protein composed of 166 amino acids. Its ~ molecular weight i8 19000 Daltons.
:i Formulated interferon iB usually stored in its lyophilized (freeze-dried) fo~. An alternative form comprises already formulated inJectable solutions.
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- 8 - 132~122 For use in the present invention, the lyophilized interferon may be reconstituted in a diluent, preferably sterile water, for administration.

The functionally recon~tituted interferon is administered systemically to young cattle by any convenient method, such as by means of a hypodermi~ syringe. The systemic administration may be made lntramuscularly, preferably into the muscles of the rump, subcutaneously, or intravenously.

Intramusculsr administration is preferred.

For the purposes of this specification young cattlo mean weaned cattle that are about three days to 18 months old, p~eferably 6 to l8 months old.

The administration of interferon may be intranasal according to the present inYentlon, although sy6temic, snd especially intramuscular administration is preferred since it 19 more convenient and, surprisingly, at least as effective as intranasal administration.

The amount of interferon administered i9 a prophylactically effective amount. The lower limit is about 0.5 mg IFN/animal, preferably about 1 mg IFN/animal, and more preferably about 3 mg IFN/animal.

The upper limit is the largest amount tolerated by the cattle without serious side effects. The upper limit is, for example, about 250 mg IFN/animal, preferably about 50 mg IFN/animal, and most preferably about lO mg IFN/animal.

The optimal amount of interferon is about 3 mg IFN/animal to 10 mg IFN/animal, preferably, about 5 m8 IFN/animal.

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2~122 _ 9 _ The functionally reconstituted lnterferon may be in any convenient concentration. For example, in order to inject 5 mg IFN/animal, lt is convenient to prepare a solution of 2.5 mg IFN/ml diluent (H20), and tG ln~ert 2 ml/animal of the solution.

As could b~ demonstrated by pharmacokinetic studies, more than 90 %
of the total amount of interferon admlnistered initially is eliminated within 15 hours after dosing.

It is, therefore, preferable to inoculate the cattle with interferon before or immediately after infection by an infectlous disease-causing mlcroorganism.

The preferred time for IFN administration ranges from -72 to +24 hours preferably from -60 to ~24 hours relative to the exposure of the animal to a pathogen.

Most preferably the cattle should be inoculated before infection by an infectious, disease-cau3ing microorganism, particularly 50 to 10 hours before infection.

The exact timing of IFN administration is important, since most re~piratory disease occurs shortly after animal mixing in ~ale barns, transportation or entry into feedlot~.

In a preferred embodiment of the present invention, the IFN
inoculation of the young cattle, therefore, occur~ at the fir~t opportunity the young cattle have to congregate prior to fattening, i.e. at the salebarn, stockyard or feedlot.

The efficiency and mode of action of intPrferon was demonstrated in i the course of the present invention by in vitro and in vivo ~ experiments.

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132~122 The cllnical efficiency of IFN administration has been supported not only by a model study using a reproducible di6ease model but also by field trials.

No treatment-related adverse reactions have been noted during cllnical field trials9 including more than 3000 calves treated intrana~ally and of approximately 7000 anlmals treated intra-muscularyO No adverse effects have been recorded in animals receiving simultaneously Interceptor~ and treatment reg1men~
associated with routine feedlot processing and fattening, such as worming, vaccination, treatment with ectopara~iticides, implanting anabollc preparatlons, branding, implanting in feed growth promotion and treatment with antibiotics.
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A controlled study demonstrated that concurrent intranasal or intram~scular treatment with Interceptor~ and vaccination with modified live IBRIPI-3 virus vaccines resulted in no harmful effects itl the animals and no impairment of the protective effects of the vaccines.

The efficiency of IF~ treatment with respect to the reduction of the incidence and severity of bovine respiratory diseasa complex results in a significant reduction in mortality rate and the number of sick days per animal or group 89 well as sn improved weight gain f and feed efficiency of the treated animals compared to the placebo Z controls.

In the case of "Enzootic Calf Pneumonia" it proves advantageous to administer Interferon on days 0, 7 and 14 related to the moment of infection by an infectious disease-causing virus or microorgani~m.
f In the following reference i8 made to specific example~, which are i included herein for purpose of illustration only and are not f intended to be limiting.
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~ 21~89-7337 Examples ~ 3291 22 1. Bovine-Interferon A me~hod ~or producing bovine interferon is disclosed in Japanese Patent Application 58,224,690 and in European Patent Application 88,~22 published September 14, 1983 and entitled "Animal Interferons, Processes Involved in Their Production, Compositions Containing Them, DNA Sequences Coding Therefore and Expression Vehicles Containing Such Sequences and Cells Transformed Thereby". The description of the preparation o~
bovine interferon from Japanese Patent Application 58,224,630 and European Patent Application 88,622 includes pages 21-37 of the European application and the corresponding pages of the Japanese publication and the references, figures and tables cited therein as well as any other description for the preparation of bovine inter~eron in these publications.
2. Pharmacokinetic and toxicity Serum dlsposition and bioavailability of rBoIFN-aI1 was studied after intranasal, intramuscular and intravenous administration of a single dose of 10 mg to grouped calves.
The respectlve half-lives were between 130 and 270 minutes. For all methods of application more than 90% of the total dose was eliminated within 15 hours after dosing Bovlne lnterferon levels fell below ~he level of detection by 24 hours after administration.
Approximately ~0% of the intramuscular dose was found to be avallable to the c1rculatory sy~tom.

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' ~329122 -lla- 21489-7337 No toxic effects ~rom interferon were seen in animals treated for 15 consecutive days with doses up to ~5 mg intranasally ~IN). The serum levels of interferon on the sixteenth day was found to be only slightly above ~he background le~el.

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: ' , , -" ~32~122 ~ 12 -Previous experiments have shown that a single intramuscular (IM~
dose up to 100 mg per head i8 well tolerated.

Translent mild leukopenia and a moderate pyrexic response are observed following an initial IM dose of interferon. Leukocyte counts and temperature return to normal within 24 hours to 4 days.
Repeated dosing does not further affect these depressions, which do not appear to influence the clinical performance of the animals nor the prophylactic value of interferon.

3. In ~itro Studies of Interferon Efficiencv a~ The antiviral activity in vitro.
The antiviral potency of rBOIFN-aI1 is assayed on bovine cell lines challenged with different viruses of bovine origin.
Activity tikres~ commonly expressed in unit U/ml or converted to units U/mg protein (speciflc activity), represent the reciprocal of the dilutions that result in 50 % inhibition of virus-induced cytophathic effects (plaques).

rBoIFN-aIl inhibits replication of the viruse3 most commonly lsolated from cattle that suffer from "BRD". (BVD~, PI-3, BRSV
and IBR/BHV-1).

b) I~munomodulatory effect in vitro To assess the immuncmodulatory effect in vitro bovine phagocytic cells (neutrophils, blood monocytes and alveolar macrophages) are treated with rBoIFN~

The effects seen are manyfold and comprise enhanced bacterial uptake by all 3 cell types and incre~sed Fc receptor activity in alveolar mscrophages, inhibition of both directed and random migration of monocytes and polymorphs, increased enzyme release ., .
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~32~22 or inactivation, increased hydrogen peroxyde generatlon and decrea~ed superoxide amine release by alvenlar macrophages and PMN leukocytes.

These effects are dose and time dependent.

4. Immunomodulatory effact ex vi~o A variety of leukocyte functions were measured throughout the cours~
of an experimental infection with BHV-l/P. haemolytica to determine whether interferon played an immunomodulatory role in vivo and thu3 resulted in rPduced morbidity and mortality.

In the model, peak immunosuppression occurs four days postinfec-tion, which i8 a time when susceptibility to bacterial infection ia maximal.

To deter~ine the effect of bovine recombinant interferon on neutro-phil migration and chemotaxis~ neutrophil3 pre~ent in the peripheral blood of interferon-treated or placebo animals are measured in a migration and chemotaxis assay.

In both cases, neutrophil function is suppressed following lnfec-tion.

In IFN treated groups, however, the neutrophil function returns to normal much more rapidly than doe~ that of the placebo groups.

~odulation of neutrophil function is further demonstrated in a chemiluminescence assay by measuring the production of reactive oxygen apecies. Vsing thi~ a~say, it is demonstrated that IFN
treatment dramatically increases the ability of neutrophil~ to produce reactive oxygen species in animals challenged with P. haamo l~tica.

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132~22 5. Field trials "Shipping ~ever"

In a flrst study, 770 steers are purchased, shipped by truck to a salebarn and then to a feedlot. On arrival animsls are randomly assigned to replicate pens. Each animal receives 5 mg of rBoIFN-~I1 per nostril in 2 ml or an equivalent volume of Placebo.

Clinical signs of depression, loss of appetite or respiratory symptoms are recorded (see annex). Sick animals ars treated wlth antibiotics.

The results are summarized in the following table 1.

Table 1 -aministered disease average utilisation daily ingredient incidencel amount of the increase of days fodder of weight per ani- (kg) mal when symptome could be recognized Placebo 38.2 0.956 6.6 O.91 rBoIFN-alphaI 31.9 0.839 6.0 l.O
No. of sick animals/total No. of animals The number of animals suffering from respiratory disease and the number of sick days per animal are significantly reduced.

Likewise weight gain and feed efficiency are improved.

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- 15 - ~ 32 ~122 In another study, conducted in a research feedlot, the effect of rBoIFN~ 10 mgIPN/animal) given as a single intramuscular injection or by intranasal instillation (5 mgIFN/nostril) with placebo are compared.

300 single sex calves in the 200 kg weight range are purchased, passed through a commercial salebarn to ensure adequate exposure to respiratory infection and trucked to the research site under conditions resembling commercial shipping practices.

The application of interferon occurs at the salebarn, 62 to 64 hours before arrival at the feedlot.

In another study IFN is administered only on arrival at the feedlot.

The percent sick animals, the number of sick days, and the percent mortality for each method of administration are compared to a control group that received no interferon. The results are shown ln the table below.

Table 2 Field Study Results of Administration of Bovine Alpha-Interferon-I
to Young Calves Experi- Time of Method of Number % No. of %
ment of Sick Admlnistr. Administr. Animals Sick Days Mortality 1 At salebarnIM 107 44 2,02 1,9 (62-64 hoursIN 106 53 2,46 0,9 beEore arrival control 106 63 2,79 5,7 at feedlot) 2 On arrival IM 100 29 1,48 0 at feedlot IN 99 28 1,61 0 control 99 53 1,70 0 Withln the ~roup~: Total No. of sick days/Mo. of animal~ over the ob~ervation period oF 21 days.

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' ` : `~ .~. , - 16 - 1 32 ~1 22 In ths course of the above described experiments it could be demonstrated that rBoIF~ I administered either IM or IN clearly reduced both the severity and the incidence of BRD during the 3 first weeks of ths study.

6. Field trials "Enzootic Calf Pneumonia"

The effect of rBoIFN-~Il against "En200tic Calf Pneumonia" is also evaluated under commercial conditions.

~0 to 80 Crossbred Simmental and Holstein dairy calves, 2 to 3 week old, welghing 50 to 65 kg, are bought from various sources, shipped to a salebarn and then brought to Clba-Geigy research station in St.Aubin, Switzerland. Only clinically healthy calves will be admitted. Any animals demonstrating signs of disease prior to the study will be excluded.

After arrlval they are welghed, individually tagged, and assigned by stratified randomization (sex, weight~ to 2 replicate pens per treatment group in a closed stable.

They are fed with unmedicamented milk replacer. Under these conditions a high proportion of the calves (70 to 90 %~ develops spontaneous "BRD" within 3 to 15 days of arrival. DAily clinical examinations are conducted for 3 weeks. The following parameters are assessed: respiratory rate, coughing, nasal discharge, temperature, apetite and behaviour (see annsx 1~.

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~329122 Table 3 Disease Inctdence . . .
Experiment ~o. Treatment2 Dose Disease1 Calves (mg) Incidence %

1 58 Control/H2Q - 16/19 ~85 IFN d 0 (lx) 0,S ll/l8 ~62~
IFN d 0 (lx) S,0 13/21 (62) 2 59 Control/H20 - 16118 ~90) IFN d 0 ~1x) 5,0 16/20 (80) IFN d 0,7,14 ~3x) 5,0 10/21 (48) 3 78 Control - 26/29 ~89) IFN d 0,4 (2x) 5,0 2012,2 (90) IFN d 0 (lx) 5,0 18/27 ~67?
_ . 1 Within the groups: No. of sick animals/total No. of animals 2 Intramuscular inJection (2 ml solution) into the neck musculature d Day(s) of treatment(s) relative to stabling (day 0) ( ;' .

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;' , ~329~22 Table 4 Morbidity/Sick ~ays Experiment No. Treatment Dose No. oE
Calves (mg? Sick Days 1 19 Control/~2O ~ 1,84 18 IFN d 0 (lx) 0,5 1,2~
21 IFN d 0 (lx) 5,0 1,14 2 18 Control/H20 - 1,2 IFN d 0 (1x) 5,0 1,1 21 I~N d 0~7,14 (3x)5,0 0,90 3 29 Control - 1,34 22 IFN d 0~4 (2x) 5,0 1,36 27 IFN d 0 (1x) 590 1 ~00 ~ithin the group3: Total No. of sick days/No. of animals over the observation period of 21 days.

All treatment groups were clinically improved when compared to the placebo controls; the cumulative incidence of disease and the number of sick days per animal were reduced.

The administration of Interceptor~ weekly at days 0, 7 and 14 roduced ~ort~li.y by op to 50 ~.

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132~22 Annex I

Description of clinical scoring system Standardized clinical examination 3 different categories of severity of symptoms are identified with normal receiving a score of 1 and the most severe receiving a score of 3.
Respiratory rate 35 ~6~ 3 Cough no cough infrequent~ painless, mild 2 severe, painful, frequent and 3 respiratory distress Nasal discharge none serous 2 mucopurulent 3 Auscultatlon normal increased bronchial tones, 2 a few dry or moist rales loud rattling noises and 3 a lot of moist rales and signs of pleuritis Body temperature 395 ~405 3 j The body temperature will be taken twice daily and the mean will be recorded.
Appetite normal ' decreased 2 anorexia 3 Behaviour normal moderately depressed 2 severely depressed moribund 3 All other clinical symptoms should also be recorded (diarrhea, , arthritis.. ~.

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132~122 Interpretation of clinical score A coefficient will be attribuated to every parameter to give an Overall Mean Value Respiration rate x 3 Cough x 1 ~asal discharge x 2 Auscultation x 2 Body temperature x 3 Appetite x 3 Behaviour x 2 Total Total/16 = overall mean value Analysis of disease development will be obtained from evolution of the overall mean value (OMV~ 7 and lts area under the curve (AUC~ and the evolution of AUC ant OMV. The comparisons between treatMents will be made by covariance analysis.
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Claims (19)

1. Injectable veterinary composition for treating young cattle prophylactically to reduce the incidence and severity of bovine respiratory disease complex comprising together with a suitable carrier customarily used in veterinary formulations a bovine interferon in an prophylactically effective amount.

2. A composition according to claim 1, wherein the bovine interferon comprises alpha bovine interferon.

3. A composition according to claim 2, wherein the alpha-bovine interferon is alpha-bovine interferon I1.

4. A composition according to claim 3, wherein the alpha-bovine interferon is a recombinant alpha-bovine interferon I1.

5. A composition according to claim 1, wherein the prophylactically effective amount of interferon is between 0.5 mg IFN/animal and 250 mg IFN/animal.

6. A composition according to claim 1, wherein the prophylactically effective amount of interferon is between 1 mg IFN/animal and 50 mg TFN/animal.

7. A composition according to claim 1, wherein the prophylactically effective amount of interferon is between 3 mg IFN/animal and 10 mg IFN/animal.

8. A composition according to claim 1, wherein the prophylactically effective amount of interferon is between 5 mg IFN/animal and 50 mg IFN/animal.

9. Process of preparing a verterinary composition according to claim 1 comprising thoroughly mixing a prophylactically effective amount of a bovine interferon with a suitable carrier customarily used in veterinary formulations.

10. Use of a bovine interferon in a prophylactically effective amount for treating young cattle to reduce the incidence and severity of bovine respiratory disease complex.

11. Use of a bovine interferon according to claim 10, wherein the bovine interferon comprises alpha-bovine interferon.

12. Use of a bovine interferon according to claim 11, wherein the alpha-bovine interferon is alpha-bovine interferon I1.

13. Use of a bovine interferon according to claim 12, wherein the alpha-bovine interferon is a recombinant alpha-bovine interferon I1.

14. Use of a bovine interferon according to claim 10, wherein the prophylactically effective amount of interferon is between 0.5 mg IFN/animal and 250 mg IFN/animal.

15. Use of a bovine interferon according to claim 10, wherein the prophylactically effective amount of interferon is between 1 mg IFN/animal and 50 mg IFN/animal.

16. Use of a bovine interferon according to claim 10, wherein the prophylactically effective amount of interferon is between 3 mg IFN/animal and 10 mg IFN/animal.

17. Use of a bovine interferon according to claim 10, wherein the prophylactically effective amount of interferon is between 5 mg IFN/animal and 50 mg IFN/animal.

18. A commercial package containing a bovine interferon in a prophylactically effective amount together with instructions for the use thereof for reducing the incidence and severity of bovine respiratory disease complex.

19. Use of a bovine interferon in a prophylactically effective amount for preparing a veterinary composition for treating young cattle prophylactically to reduce the incidence and severity of bovine respiratory disease complex.