RU2264227C1 - Mixed vaccine based on antigens of microorganism moraxella bovis and herpes virus type i for specific prophylaxis of infectious keratoconjunctivitis in cattle - Google Patents

Abstract

FIELD: veterinary microbiology, virology, biotechnology.

SUBSTANCE: invention proposes vaccine that comprises as antigens the following components, vol. %: inactivated suspension of cells of hemolytic strains of microorganism M. bovis with the total concentration 100-120 billion cells in 1 cm³: strain M. bovis "G97-VNIVI", 4.0-5.0; strain M. bovis "SHZ-01", 4.0-5.0; inactivated cultural suspension of the strain Herpesvirus bovis type I "TKA-VIEV-V2" with infectious titer 10^7.0 - 10^7.5 TCD₅₀/ml, 78.0-83.0; 6% solution of aluminum hydroxide gel, the balance. Vaccine enhances accumulation of specific protective antibodies in serum blood of vaccinated animals and provides the development of immunity against infectious keratoconjunctivitis that is retained for one year.

EFFECT: enhanced effectiveness and valuable properties of vaccine.

4 tbl, 6 ex

Description

The invention relates to the field of veterinary microbiology, virology and biotechnology, in particular to the production of a vaccine for the specific prophylaxis of infectious keratoconjunctivitis in cattle. It was established that the main etiological causative agents of the disease are hemolytic forms of bacteria Moraxlla bovis against the background of intense solar UV radiation. Infectious keratoconjunctivitis is widespread in all countries of the world. The frequency of its manifestation in the Russian Federation is highest among young cattle in feedlots with a high population density, and the intensity of the development of the epizootic process depends on the degree of exposure of animals in the summer months to the extreme flux of solar UV rays, and the disease covers from 25 to 90% of the population.

Along with this, it has been proven that the cattle infectious rhinotracheitis virus (herpesvirus type 1) can also cause acute conjunctivitis in this animal species. However, the inflammatory process does not progress to corneal opacity and ulceration, as is the case with infectious keratoconjunctivitis (Jensen R., Mackay D. Cattle diseases in industrial feeding. M .: Kolos, 1977, p. 127-129 ; Abinanti FR, Plumer GJ: The isolation of Infectious Bovine Rhinotracheitis Virus from Cattle Affected with Conjunctivitis-Observations on the Experimental Infection. // Am. J. Vet Res., 1961, 22, p.13-17; Hughes JP et al. Keratoconjunctivitis Associated with Infectious Bovine Rhinotracheitis. // Am. J. Vet. Med. Ass., 1964, 45, p.32-42; George W. et al. Bovine Infectious Keratoconjunctivitis: Interaction of Moraxella bovis and Infectious Rhinotrachitis Virus. // Am. J. Vet. Res., 1970, 31, No. 4 - p. 653-662).

Research conducted in the 80s on the problem of infectious keratoconjunctivitis in cattle showed that the infectious rhinotracheitis virus is one of the pathogens that, together with the bacteria Moraxella bovis, causes this disease (Straub O.H. Cattle infections caused by the virus herpes. - M .: Kolos, 1981, - p. 33-35).

Other literature also suggests that the infectious rhinotracheitis virus may be the primary causative agent of conjunctivitis, but not keratoconjunctivitis (Rebnun W. et al. Anoutbreak of the conjunctivitis form of infectious bovine rhinotraheitis. // Cornell. Veter., 1978, 68, 3 , - p. 277-307). A number of works suggest that the virus of infectious rhinotracheitis in cattle creates a particularly favorable environment for the pathogenic action of the main causative agent of keratoconjunctivitis - bacteria Moraxella bovis.

Later it was proved that chlamydia can also play a less pronounced etiological role in infectious keratoconjunctivitis in cattle (Wehr I. et al. Untersuchungen zur Bedeutung der Chlamidien bei der infektiosen Keratokonjunctivitis des Rindes. // Wissensch. Humbold. Univ. 1980. 29, 1, - p. 61-65), Mycoplasma bovoculi (Langford EV Characterization of mycoplasma isolated from infectionus bovine keratoconjunctivitis: M. bovoculi sp. Nov. // Can. J. Microbiol., 1973, 19, - p. 1435 -1444), rickettsia and opportunistic bacteria, participating mainly in the formation of mixed infections.

The unencrypted etiology of infectious keratoconjunctivitis in our country, the absence of any regulatory documents on its diagnosis and control measures, the importation of breeding stock from Western European countries - hidden carriers of the pathogen, led to the appearance of vast foci that are permanently unfavorable for infectious keratoconjunctivitis and continued the trend of the further spread of the disease, causing significant economic damage due to reduced milk yield and increase in live weight of animals due to partial or complete vision loss (Bobyr V.K.Infectious keratoconjunctivitis of cattle in the farms of the Gomel region. // Diseases of agricultural animals and birds, their prevention and treatment. / Collection of works of LVI, issue 39. - L., 1974, - p.167-179; Andrisyan VB Infectious keratoconjunctivitis of cattle in the North-Western zone of the RSFSR // Collection of scientific works LVI. - L., 1988, - p.6-11; Kakulin T.E. Infectious keratoconjunctivitis of calves in the Irkutsk region. // And the book: Prevention of diseases of young animals of agricultural animals of Siberia and the Far East. Novosibirsk, 1982, p. 73-75; Gaffarov Kh.Z. et al. Epizootological aspects of infectious keratoconjunctivitis in cattle. // Materials of the International scientific conference dedicated to the 125th anniversary of the KSAVM. Kazan, 1998, p.29-31; Gaffarov Kh.Z., Spiridonov G.N., Valebnaya L.V. The bacterial strain Moraxella bovis "G97-VNIVI" used for the manufacture of diagnosticums and vaccines against infectious keratoconjunctivitis in cattle. // Patent for the invention of the Russian Federation No. 2145353, priority dated September 15, 1998; Gaffarov Kh.Z., Valebnaya L.V., Spiridonov G.N. Infectious keratoconjunctivitis in cattle in the Middle Volga and Ural regions. // Actual problems of diseases of young animals in modern conditions. Materials of the international scientific-practical conference September 23-25, 2002, Voronezh, - p.188-191).

Epizootological monitoring carried out in relation to KIC in 48 households in 12 districts of the Republic of Tatarstan and 29 households in 8 districts of the Republic of Bashkortostan and the Udmurt Republic showed that the incidence of calves 1-5 months of age is 50-85%, in older calves - 20-25% and among dairy herds, it ranges from 12-15% (Gaffarov Kh.Z., Valebnaya L.V., Spiridonov G.N. Infectious keratoconjunctivitis in cattle in the Middle Volga and Ural regions. // Actual problems of young animals in modern . Loviyah Proceedings of the international scientific-practical conference on 23-25 September 2002, Voronezh - s.188-191).

Given that infectious keratoconjunctivitis is widespread and affects all age groups of animals, especially young animals, vaccination is considered as a very effective method of combating it. It should be noted that the problem of specific prevention of infectious keratoconjunctivitis in many countries of the world was already solved in the 70-90s of the last century (Hughes D.et. al. Experimenally Induced Bovine Infectious Keratoconjunctivitis: Effectivenes of Intramuscular Vaccination with Viable Moraxella bovis Culture. // Am. J. Vet. Res., 1971, 32, No. 6, p. 879-886; Pugh GW et al. Infectious bovine keratoconjunctivitis in cattle vaccinated and medicated against Moraxella bovis befare parturition. // Am. J. Vet. Res., 1982, 43 No. 2, p. 320-325; Gwin R. Medicament and method for prodicing immunity the infectious bovine keratoconjunctivitis. // US Patent No. 4539201 of September 3, 1985). Therefore, the problem of creating a vaccine against infectious keratoconjunctivitis in cattle in the Russian Federation is very relevant. Domestic analogues of vaccines against infectious keratoconjunctivitis in cattle, made on the basis of hemolytic forms of bacteria Moraxella bovis, do not exist before our studies. The closest analogue to the proposed "Associated vaccine for the specific prevention of infectious keratoconjunctivitis of cattle based on the bacterial antigens Moraxella bovis and herpesvirus type 1" can serve as the US patent "Moraxella bovis infectious bovine keratoconjunctivitis steam-killed bacterin" 340121, 10 018, 1018 which describes the fact of using the immunizing antigen Moraxella bovis, in particular bacterin, which is used as a prophylactic against infectious keratoconjunctivitis in cattle. Bacteria are a steam-inactivated suspension of Moraxella bovis bacteria for one hour. Bacteria are able to create immunity against infectious keratoconjunctivitis for 6 months. The disadvantage of this vaccine is that it does not protect animals from keratoconjunctivitis of herpes virus etiology.

The objective of the invention is to provide an associated vaccine based on the hemolytic forms of bacteria Moraxella bovis and herpesvirus type 1, designed to create specific prophylaxis of infectious keratoconjunctivitis in cattle in the Russian Federation, and increase the duration of immunity up to 12 months.

The technical result of the invention is to obtain an associated vaccine with high immunogenic activity, and the expansion of its immunogenic spectrum.

The essence of the invention is as follows: the associated vaccine against infectious keratoconjunctivitis in cattle contains antigens of hemolytic forms of bacteria Moraxella bovis and herpes virus of cattle, deposited on aluminum hydroxide, in the following ratio, vol.%:

Inactivated cell suspensions bacteria M.bovis concentration 100-120 billion m. in 1 cm ³ : pcs. "G97-VNIVI" - 4.0-5.0 pcs. "Ш3-01"  4.0-5.0 Inactivated culture herpesvirus suspension large cattle pcs TKA-VIEV-V2 with an infectious titer of 10 ^7.0 -10 ^7.5 TCD ₅₀ / ml 78.0-83.0 Gel of aluminum hydroxide, 6% solution rest

For the manufacture of an associated vaccine for specific prophylaxis of cattle infectious keratoconjunctivitis based on the antigens of bacteria Moraxella bovis and herpesvirus type 1, the patented bacterial strain Moraxella bovis "G97-VNIVI" is used (RF Patent for invention No. 2145353 with priority dated September 15, 1998) and a new strain of bacteria Moraxella bovis "Ш3-01" obtained from a patient with an infectious calf keratoconjunctivitis. The bacterial strain Moraxella bovis "Ш3-01" is characterized by the following properties: these are short thick sticks 1.5-2.0 in length and 0.5-1.0 μm in diameter with rounded ends, arranged in pairs or in the form of short chains, no spores form, motionless, stained gram-negative. On blood MPA at a pH of 7.2-7.6 after 24 hours of incubation at 37 ° C, colonies with a diameter of 1 to 3 mm with a β-hemolysis zone 0.5 to 2.0 mm wide are formed. The colonies are smooth, round, shiny, grayish-white. On the BCH, after a 24-48 hour incubation at 37 ° C, turbidity of the broth is observed with the formation of a small precipitate. The optional aerobic strain does not ferment sugars, does not restore nitrates to nitrites, does not form indole, liquefies gelatin, i.e. possesses proteolytic activity, peptonizes litmus milk, gives a positive reaction to oxidase, which are characteristic for microorganisms of the family Neisseriaceae, genus Moraxella. The strain is virulent for white mice, causing their death within 24 hours after intraperitoneal administration of a daily agar culture at a dose of 500 mln.m.

Example 1. Obtaining matrovogo seed of each strain of bacteria Moraxella bovis.

For the manufacture of the vaccine take ampoules with lyophilized cultures of production strains of M. bovis; "G97-VNIVI" and "Ш3-01", which are dissolved in 0.5-2.0 cm ³ MPB and transferred to Petri dishes with 10% blood MPA. Cultivation is carried out for 16-18 hours, then the cultures are checked for compliance with morphological, cultural, enzymatic and virulent properties. If they correspond to the hemolytic forms of M. bovis bacteria, then they are used to obtain the bacterial mass necessary for the manufacture of the associated vaccine.

The strains are stored in lyophilized form. For this, a suspension of daily culture of bacteria Moraxella bovis with a concentration of 50 billion m ³ in 1 cm ^{3 is} mixed with a protective medium (skim milk with sucrose 5%, gelatin 1.5%) in a ratio of 1: 1, packaged in ampoules of 1 cm ³ , dried by sublimation, sealed ampoules under vacuum and stored at a temperature of + 2-8 ° C.

Example 2. Cultivation of the bacterial mass of each strain of bacteria Moraxella bovis separately and its inactivation.

To obtain biomass of M. bovis cultures, MPA containing 10% defibrinated sheep blood is used. For this purpose, the indicated medium is poured into sterile conditions into 1.5 liter mattresses of 250-300 cm, after solidification of the medium, the strains of these strains are seeded by adding 2 cm ^{3 of a} bacterial suspension containing 1 billion mc. To each mattress. 1 cm ³ . Crops are kept in a thermostat at a temperature of 37 ° C. After 36-48 hours, the grown colonies of M. bovis cultures are washed off with a 0.02% sodium chloride solution, and a suspension is prepared with a concentration of 100-120 billion m. in 1 cm ³ according to the bacterial or optical standard turbidity GISK them. Tarasevich. The culture is checked for purity, morphological and serological typicality.

Inactivation of bacterial suspensions is carried out with formalin. For this, formalin with a content of 37-38% active formaldehyde of 0.5 cm ³ per 100 cm ^{3 of} suspension is added to the microbial suspension. Stirred and placed in a thermostat for 72 hours. Then take a sample for completeness of inactivation, which is carried out by plating inactivated microbial suspensions on blood MPA.

Example 3. Preparation of a native suspension of herpes virus in cattle and its inactivation.

Cattle herpesvirus (pcs. TKA-VIEV-B2) is propagated in a transplanted culture of a cow embryo tracheal cell (line TR) grown in three-liter roller bottles on a combined growth medium consisting of 199 - 10% medium, GLA - 40% , medium MEM needle - 40% and cattle serum - 10%. The culture is grown for 3-4 days at a sowing concentration of 140-150 thousand cells in 1 cm ³ environment. The growth medium is poured out, a support medium is introduced (media 199 - 20%, GLA - 40% and MEM Needle - 40%) in an amount of 350-370 cm ³ , into which herpes virus is previously added at the rate of 10 cm ³ per 500 cm ^{3 of} medium, 3 % glutamine solution - 5 cm ³ and antibiotics (streptomycin - 100 μg / cm ³ , penicillin - 100 PIECES / cm ³ ). The bottles are incubated in a roller unit at 37-38 ° C for 3-4 days. The culture fluid is collected by freezing and thawing three times during a period of pronounced cytopathic effect - the maximum accumulation of the virus. The resulting viral suspensions are combined and, in order to inactivate the virus, formalin with an active formaldehyde content of 37-38% is added at the rate of 0.5 cm ³ per 100 cm ^{3 of the} viral suspension, stirred and left for 24-36 hours at room temperature, and then checked for bacterial and fungal contamination. To prepare a vaccine, a viral suspension is taken without contamination. The completeness of inactivation of herpes cattle is monitored by 3 consecutive passages of an inactivated virus suspension sample used for the manufacture of an associated vaccine against cattle keratoconjunctivitis on a transplanted cow embryo tracheal cell culture (TR line) with an interval of 5-6 days. A viral suspension is considered inactivated if the cytopathic effect of the virus is not detected in the third passage.

Example 4. The preparation of an associated vaccine for the specific prevention of infectious keratoconjunctivitis in cattle based on the antigens of bacteria Moraxella bovis and herpesvirus type 1.

The vaccine is prepared from the cattle herpes virus antigen with an infectious titer of 10 ^7.0-7.5 TCD ₅₀ / ml and production strains of the bacteria Moraxella bovis: "G97-VNIVI", "Sh3-01".

A herpes virus suspension is taken, a 100-120 billionth suspension of Moraxella bovis bacteria is added to it based on the calculation of 4-5 cm ^{3 of} each strain per 100 cm ^{3 of the} vaccine preparation, as well as 6% aluminum hydroxide gel at the rate of 10 cm ³ per 100 cm ³ vaccine. The pH of the vaccine is adjusted to 7.2-7.4 and packaged with thorough periodic stirring into bottles, which are then closed with rubber stoppers, wrapped in metal caps and labeled. Table 1 shows the composition of the vaccine.

Table 1
The composition of the associated vaccine for the specific prevention of infectious keratoconjunctivitis in cattle based on the antigens of bacteria Moraxella bovis and herpesvirus type 1 Vaccine components Their content in 1 liter of vaccine (in ml) Antigens of M. bovis, containing in 1 cm ³ 100-120 billion m. PCS. "G97-VNIVI" 40-50 PCS. "Ш3-01" 40-50 Bovine Herpesvirus antigen pcs. TKA-VIEV-B2 with an infectious titer of 10 ^7.0-7.5 TCD ₅₀ / ml 780-830 6% aluminum hydroxide gel solution Rest

Example 5. The control of the vaccine for sterility, safety and antigenic activity.

To test for sterility, from 6 bottles of vaccine of each series, cultures of 0.2 cm ^{3 are made} on MPB, MPA, blood MPA, MPPB under paraffin oil and Saburo agar, 2 tubes per bottle. Crops with all media are kept in a thermostat at 37 ° C, and with Saburo agar - at 20-22 ° C for 15 days. Culture media should remain sterile.

To test for harmlessness, 10 white mice with a live weight of 17-18 g are selected and a vaccine is injected subcutaneously at a dose of 0.5 cm ³ . The vaccine is considered harmless if the mice remain alive and clinically healthy for 10 days after administration of the vaccine.

The antigenic activity of the vaccine is monitored on 3 rabbits with a live weight of 2.0-2.5 kg, to which the drug is administered subcutaneously at a dose of 2 cm ³ twice with an interval of 14 days. 14 days after the last vaccination, blood was collected from the ear vein in rabbits and the serum was examined to determine the level of specific antibodies to herpesvirus type 1 and Moraxella bovis bacterial antigens. Antibody titers of cattle herpes virus should be in the range of 1: 320-1: 640 in ELISA, for strains of bacteria Moraxella bovis - 1: 400-1: 1600 in the ELISA reaction.

The control results of 24 experimental vaccine series showed that all series of the biological product were sterile, harmless and antigenically active. Indicators of antigenic activity of the associated vaccine are presented in table 2.

A production test of the experimental vaccine series was carried out in 8 farms of the Republic of Tatarstan and in one of the Chuvash Republic, which were disadvantaged for infectious keratoconjunctivitis in cattle, where the incidence of calves up to 6 months of age was 24-56%, young animals under 12 months of age were 19-35% and young animals older than a year and an adult livestock of 8-22%. The entire livestock of cattle in these farms was vaccinated with an associated vaccine before driving to the pasture twice with an interval of 21-30 days in doses: calves up to 6 months of age - 3 cm ³ , young animals from 6 to 12 months. - 5 cm ³ , young animals older than a year and adult livestock - 10 cm ³ . The test results of the vaccine in these farms are presented in table 4. From the table it follows that the associated vaccine has a high immunogenic activity. Its prophylactic use in 9 permanently dysfunctional households made it possible to completely eradicate the disease in 6 households, and in the remaining three to reduce the disease to isolated cases.

Example 6. The purpose, general information and procedure for the use of the associated vaccine for the specific prevention of infectious keratoconjunctivitis in cattle based on the antigens of bacteria Moraxella bovis and herpesvirus type 1.

The vaccine is intended for specific prophylaxis of cattle infectious keratoconjunctivitis caused by a mixed infection caused by the bacteria Moraxella bovis and the infectious rhinotracheitis virus (herpes virus type 1) against the background of increased solar ultraviolet radiation in the summer months.

The vaccine is a mixture of concentrated antigens of hemolytic forms of M. bovis bacteria and a culture suspension of herpesvirus type 1 in optimal proportions.

In appearance, the vaccine deposited with aluminum hydroxide is an opaque liquid with a white precipitate, which, when the bottle is shaken, easily breaks up, forming a homogeneous suspension of a pale pink color.

The vaccine is produced in glass bottles of 100, 200 and 500 cm ³ with tightly closed rubber stoppers, rolled in metal caps, and labeled in accordance with TU.

The vaccine is suitable for use within 12 months from the date of manufacture, subject to storage and transportation at a temperature of 2-10 ° C.

The vaccine is used as a preventive measure in threatened and permanently dysfunctional farms for infectious keratoconjunctivitis in cattle. Vaccinate all nascent young growth at the age of 30-35 days, regardless of the time of year, as well as the entire number of cattle before pasture on the pasture. The vaccine is administered subcutaneously in the middle third of the neck twice with an interval of 21-30 days in doses:

- 3 cm ³ - calves aged 1 to 6 months;

- 5 cm ³ - young animals aged 6 months. up to a year;

- 10 cm ³ - young animals older than a year, cows and bulls producers.

The vaccine provides immunity in young and adult livestock of cattle, which persists for a year.

For the period 1999-2003 814.5 liters of the associated vaccine were produced, which was used on the farms of the Republic of Tatarstan, Mari El, Bashkortostan, Udmurtia and Chuvashia, which were unsuccessful for infectious keratoconjunctivitis in cattle (table 3).

table 2
Indicators of antigenic activity of an associated vaccine for specific prophylaxis of infectious keratoconjunctivitis in cattle based on bacterial antigens Moraxella bovis and herpesvirus type 1 in experimental conditions. Animal species Antibody titers (M ± t) in ELISA KM bovis pcs. T97-VNIVI " to M.hovis pcs. "Ш3-01" to herpesvirus pcs. TK-VIEV-V2 Before vaccination After 1 vaccination After 2 vaccinations Before vaccination After 1 vaccination After 2 vaccinations Before vaccination After 1 vaccination After 2 vaccinations Rabbits - 280.00 ± 82.15 2720.00 ± 1117.32 - 1360.00 ± 558.56 5440.00 ± 1073.0 - 160.00 ± 0.00 576.00 ± 208.61 Cattle 5280.00 ± 1252.19 10,240.00 ± 1,752.00 6400 ± 0.00 8320.00 ± 2146.00 160.00 ± 80.00 896.00 ± 175.27 960.00 ± 226.27

Table 3
Disease cattle infectious keratoconjunctivitis points where a widespread production trial of the associated vaccine was conducted. No. p / p Name of households Amount of vaccine used, in liters 1 2 3 Republic of Tatarstan 1 KP "Menger" of the Atninsky district 4.0 2 KP "Vanguard" of Aktanyshsky district 12.0 3 KP them. Lenin Buinsky district 10.0 4 LLC "Jalil" of the Bugulma district 25.0 5 Uchkhoz KGAVM Vysokogorsky district 25.0 6 AKP "Tsilna" of Drozhzhanovsky district 18.0 7 Drozhzhanov State Light Association 26.0 8 GUL "Vetbiopharm" Kazan 320,0 nine KP "Shirdansky" Zelenodolsky district 30,0 10 KP "Vegetable grower" Zelenodolsky district 18.0 eleven SKHPK "Council" of Zelenodolsk district 10.0 12 SKHPK named after Vakhitov, Kukmorsky district 20.5 thirteen PE "Sadykova H.M." Laishevsky district 20,0 14 SHP "Devyatovskoe" Laishevsky district 15.0 fifteen KH "Kaipskoe" Laishevsky district 5,0 16 TNV "Wafin and K" Laishevsky district 15.0 17 Narmanka OJSC, Laishevsky district 20,0 eighteen KH "Spectrum" of Laishevsky district 5,0 19 Idel LLC, Laishevsky district 12.0 twenty LLC "Birch" Laishevsky district 10.0 21 SHK "im.Sindryakova" Nurlatsky district 10.0 22 KP "AK YAR" Novoshishminsky district 6.0 23 KHT "Yutaza" Yutazinsky district 4.0 24 SEC "Tugay" of the Yutazinsky district 10.0 Dyurtyulinsky district of the Republic of Bashkortostan 25 SPK "Kushul" 20,0 26 SPK "Plemzavod named after Lenin" 20,0 27 SPK "them. Enikeevka" 30,0 28 SPK "Plemzavod Pobeda" 30,0 Republic of Udmurtia 29th KP "Bolshevik" of the Alnash region 20,0 thirty KP "Young Guard" of the Alnash region 10.0 31 KDP "May 1" Novo-Toryalovsky district of the Republic of Mari El 14.0 32 SHPK "Star" of the Mariinsko-Posadsky District of the Republic of Chuvashia 20,0 Total 814.5

Table 4
The efficacy indicators of the use of the associated vaccine for the specific prophylaxis of infectious keratoconjunctivitis in cattle based on the antigens of the bacteria Moraxella bovis and herpesvirus type 1 No. Name of the farm Livestock, heads Incidence,% before vaccine after vaccine calves up to 6 months of age young animals up to 12 months. age young animals over 12 months of age and cows calves up to 6 months of age young animals up to 12 months. age young animals over 12 months of age and cows 1 SKHPK "Devyatovskoe" 1319 35-45 28 16 3-4 - - 2 KH "Kaip" 173 38 35 8 - - - 3 TNV "Wafin and K" 1148 32 27 thirteen - - - 4 Narmanka OJSC 2560 56 34 22 - - - 5 KH "Spectrum" 213 24 19 14 - - - 6 Idel LLC 884 38 32 19 - - - 7 SKHPK "named after Vakhitov" 2970 35-50 25-27 10-15 2-3 2 - 8 SHPK "Star" 1237 35 thirty twenty - - - nine "Uchkhoz KGAVM" 1198 40-45 20-25 10-12 2-3 - -

Claims (1)

Associated vaccine for specific prophylaxis of cattle infectious keratoconjunctivitis based on the antigens of bacteria Moraxella bovis and herpesvirus type I, characterized in that it contains inactivated cell suspensions of the hemolytic bacteria strains Moraxella bovis "G97-VNIVI" and Moraxella bovis "Ш3-01 "with a total concentration of 100-120 billion cubic meters in 1 cm ³ inactivated culture suspension of herpes virus type I pc. "TKA-VIEV-B2" with an infectious titer of 10 ^7.0-7.5 TCD ₅₀ / ml, as an adjuvant - 6% solution of aluminum hydroxide gel in the following ratio, vol.%: Inactivated hemolytic cell suspensions bacterial strains of M. bovis with a total concentration 100-120 billion m. K. in 1 cm ³ : PCS. M.bovis "G97-VNIVI" 4.0-5.0 PCS. M.bovis "Ш3-01" 4.0-5.0 Inactivated culture suspension Herpesvirus bovis type I "TKA-VIEV-B2" with infectious titer 10 ^7.0-7.5 TCD ₅₀ / ml 78.0-83.0 Gel of aluminum hydroxide, 6% solution Rest