Strain "vniizzh" of cattle coronavirus for preparing diagnostic, vaccine and curative preparations

FIELD: veterinary virology and biotechnology.

SUBSTANCE: invention proposes the strain that possesses high antigenic and immunogenic activity. The strain is deposited in the Collection of microorganism strain FGU VGNKI at the registration name "VNIIZZH-DEP". The coronavirus strain is reproduced in transplanted cell cultures of calf kidney (MDVK, Taurus), calve coronary vessel cells and in heterologous culture of simian cells (Vero). After 3-4 days of incubation at 37°C virus is accumulated in the amount up to 108 particels/cm3 by data of electronic microscopy. The strain shows ability for reproducing in the same accumulation degree in cell culture MDVK at 34°C. The strain possesses high biological, antigenic and immunogenic activity and retains native immunobiological properties after inactivation and can be used in preparing highly sensitive and specific diagnostic, highly immunogenic, harmless and areactogenic vaccine and curative preparations.

EFFECT: valuable properties of strain, improved preparing method.

6 tbl, 4 ex

 

The invention relates to the field of veterinary Virology and biotechnology and can be used in the design and manufacture of diagnostics, prophylaxis and treatment of coronavirus infection in cattle (cattle).

Coronavirus infection of cattle is manifested in the form of coronavirus diarrhea of newborn calves and coronavirus winter dysentery of adult cattle.

Coronavirus diarrhea of newborn calves - OSTROBRAMSKA contagious disease characterized by lesions of the gastrointestinal and respiratory tracts. The disease is widely distributed in many countries of the world.

Winter dysentery of adult cattle - OSTROBRAMSKA contagious disease, characterized by the oppression of the body, diarrhea and a sharp decline in milk production.

Extremely widespread, the ability to long-term persistence in animals-convalescents, the relative resistance of the pathogen to the effects of various factors cause enzootic disease in farms with disadvantaged conditions of animals.

It is known that coronaviruses cattle have close biological and antigenic relationship with coronaviruses other animal species and humans. A study of the antigenic relationship between the coronaviruses of man and animal are established, what, for example, strain OS-43 coronavirus person has antigenic relationship with the coronavirus that causes diarrhea of newborn calves. The presence of common antigenic determinants is set in RN, RAC, rtga and confirmed by detection of seroconversion in people with coronavirus infection.

Although the value of coronaviruses cattle as causes of human disease at the present time is not precisely defined, but the potential danger of these viruses to humans has important epidemiological significance, especially in rural areas.

In this regard, the most important conditions for successful control of this disease are timely and correct diagnosis, measures of specific prophylaxis and treatment, which in turn implies obtaining a sufficient number of active viral antigen.

Great importance is attached to the intake of the calves colostrum with a high content of specific antibodies for at least two weeks, so as soon as antibodies, entered calves oral, protect them from disease. This provision defines the strategy and development of specific prevention. Specific protection of newborn calves during the first days of life is carried out by active immunization of mothers in order to encourage their formation of antibodies and to ensure the transfer of the colostrum. For the vaccination of cows spend in the second half of pregnancy.

For specific prevention coronavirus diarrhea of newborn calves used live and inactivated vaccines, which impart globorotalia cows. These vaccines are usually prepared from actual production strains coronavirus infection, antigenic properties which correspond to the antigenic properties of epizootic strains of the pathogen (1).

A known strain Mebus of coronavirus cattle for the manufacture of vaccines (2).

A known strain BCV-9 (CAPM V-280) coronavirus cattle for production of vaccines(3, 4, 5).

A known strain VGNKI 8 (KP-83) of coronavirus cattle for the manufacture of vaccines (6).

A known strain 50-3 of coronavirus cattle for the manufacture of vaccines (7, 8).

Known strains of types I, II and III of coronavirus cattle for the manufacture of vaccines (9).

A known strain "CM-1" coronavirus cattle for the manufacture of vaccines (10).

A known strain of ATSS VR 874 of coronavirus cattle for production of diagnostic and vaccine preparations (11).

A common disadvantage of the known strains is low epidemic efficiency made on the basis of their vaccines, due to lack of antigenic and immunogenic activity of sleds is of a low level of accumulation of the virus in the system of reproduction.

In this regard, an important issue is finding new coronavirus cattle, suitable for the manufacture of vaccine and therapeutic drugs, and diagnostic tools.

In the task of creating the present invention was to obtain a new production strain of coronavirus cattle with high biological, antigenic and immunogenic activity. These properties largely are provided by the selection of an effective system of reproduction of the virus and optimization of the method of cultivation.

The technical result from use of the present invention is to expand the Arsenal of industrial strains of coronaviruses cattle with high biological, antigenic and immunogenic activity, preserving their native immunobiological properties after inactivation and suitable for the manufacture of highly sensitive and specific diagnostic, highly immunogenic, safe and reactogenic vaccine and therapeutic drugs that can protect cattle from epizootic pathogen coronavirus infection, circulating on the territory of Russia.

This technical result is achieved by obtaining strain "ARRIAH" (author's name) coronavirus cattle. Strain "ARRIAH" coronavirus cattle is new, not previously known.

The source who is oditel to obtain strain "ARRIAH" isolated from the feces of a newborn calf with dysfunction of the gastrointestinal tract.

Production strain "ARRIAH" coronavirus cattle obtained by adapting to the transplantable cell cultures of calf kidney MDVK.

The resulting strain deposited at the Russian state collection of strains of microorganisms used in veterinary medicine and animal production, Federal VGNKI the Ministry of agriculture of the Russian Federation on 12 March 2001 under the registration name "ARRIAH-DEPT".

Strain "ARRIAH-DEPT" of coronavirus cattle has a high biological, antigenic and immunogenic activity and retains its native immunobiological properties after inactivation.

Experimentally confirmed the possibility of its use for the manufacture of diagnostics, prophylaxis and treatment of coronavirus infection of cattle.

Strain "ARRIAH-DEPT" of coronavirus cattle is characterized by the following characteristics and properties.

Morphological properties

Strain "ARRIAH - DEPT" of coronavirus cattle belongs to the family Coronaviridae, genus Coronavirus and has morphological features characteristic of the pathogen coronavirus infection of cattle: spherical or pleomorphic virion diameter of 80-100 nm consists of a helical nucleocapsid symmetry and lipoproteidna shell on the surface of which are club-shaped protrusions with a length 12-24 nm, forming the likeness of the solar corona. Floating density of virions in the sucrose to 1.15-1.18 g/cm .

In the composition of the virions detected three structural proteins palaminy glycoprotein E2 (180-200 KD); nucleocapside the phosphoprotein N (50-60 KD) and matrix glycoprotein E1 (23-30 KD).

Antigenic properties

The antigen of bovine coronavirus strain "ARRIAH-DEPT" induces in the body of Guinea pigs and rabbits education virousspecificakih antibodies detected in the reaction of inhibition of haemagglutination (rtga) in the credits from 5 to 6 log2and from 6 to 7 log2respectively.

In the blood serum of globorotalia cows through 26 days after revaccination antibodies to coronavirus in rtga revealed in the credits from 5 to 8 log2and in colostrum - 10 log2. Timely fed a colostrum provides a high level colostral antibodies (up to 8 log2in the body of newborn calves.

Biotechnological characteristics

Strain "ARRIAH-DEPT" of coronavirus cattle intended for the manufacture of inactivated vaccines against coronavirus infection of cattle, diagnostic antigens and sera and antibody preparations used for the treatment of sick calves.

Strain "ARRIAH-DEPT" of coronavirus cattle shows high biological, antigenic and immunogenic activity as in the native form and after inactivation.

Coronavirus strain "ARRIAH-DEPT" reproducerea in transplantable cell cultures kidney tion is a (MDVK, Taurus), coronary vessels of the calf (CRP) and in heterologous cell culture monkey (Vero). At 37°C for 3-4 days incubation the virus accumulates in the amount of up to 108particles/cm3(data from electron microscopy studies).

Strain "ARRIAH-DEPT" of coronavirus cattle has the ability to culture cells MDVK be reproduced with the same degree of accumulation at 34°C. the Period of reproduction at that temperature increases almost by the day, but allows you to get double the yield of the virus by changing a supportive environment. "Drain" has a high biological, immunogenic and antigenic activity.

Resistance to external factors

Strain "ARRIAH-DEPT" of coronavirus cattle shows maximum stability in the pH range from 6.0 to 7.2. Acid (3,0) and alkaline (11,0) environment have on the virus inactivating effect. The pathogen is resistant to trypsin. The virus is destroyed by lipid solvents: chloroform, methylene chloride, ether, tween and Triton X-100.

Inactivated coronavirus strain "ARRIAH-DEPT" stable during storage at 4°as in the native state, and in the composition of inactivated vaccines.

Additional characteristics and properties

Antigenic activity has antigenicity in the composition of inactivated vaccine and treatment for hyperimmunization the donors diagnostic and therapeutic sera.

Reactogenicity - reactogenic properties is not.

Stability - maintains the original biological (antigenic) properties when passirovannye in cell culture MDVK within 30 passages (observation period).

Pathogenicity is expressed.

Virulence is expressed.

Contagiousness is expressed.

Carcinogenesis is missing.

Free from contamination by bacteria, mycoplasmas and other hemagglutinins viruses.

Based on the obtained data it can be argued that the strain "ARRIAH-DEPT" antigenic and immunological spectra is original, in taxonomic terms, a new previously unknown strain.

The use of diagnostic and vaccine preparations from strain "ARRIAH-DEPT provides high efficiency measures to combat coronavirus infection of cattle.

According to the applicant, the proposed strain meets the conditions of patentability of "novelty" and "inventive step".

The essence of the invention is illustrated by examples of its use.

Example 1

Obtaining strain "ARRIAH-DEPT" in the cell culture MDVK

Strain "ARRIAH" coronavirus isolated from cattle feces samples from a newborn calf with dysfunction of the gastrointestinal tract. When isolation of the pathogen was used complex virological methods outlined in the "Guide is TBE indication of the causative agents of especially dangerous diseases of agricultural animals in veterinary stations", approved the BS HA PC USSR on March 15, 1990

To this end, the suspension of faeces was passed through the filter FPP-15-1,5. Sorbed coronavirus was suirable the Hanks solution. The volume of the eluate was 1/100-1/200 volume of a suspension of faeces. In the purified eluate was added antibiotics, kept at 37°With 2-4 hours. To the suspension was added trypsin to a concentration of 15-20 mg/cm3and thermostatically at 37°C for 30 minutes. Before infecting the cell culture MDVK twice washed from the growth serum with Hanks solution. After infection in cell culture MDVK made supporting nutrient medium containing trypsin at a concentration of 10-15 mg/cm3. The vessels were incubated at 37°until changes in the cells. Received vaccinated suspension was freeze-thawed and used for subsequent passages. After 8 passages in cell culture MDVK strain "ARRIAH-DEPT" of coronavirus cattle possessed the following characteristics: the title reaction of haemagglutination with erythrocytes mouse 7-10 log2the accumulation of the virus in cell culture 107,5-9particles/cm3(the electron microscopy data).

Example 2

Study of the adaptation of the strain properties "ARRIAH-DEPT" of coronavirus cattle

The use of trypsin in the process of cultivation of the strain "ARRIAH-DEPT" of coronavirus cattle allowed us to widen the circle sensitive is it transplantable cell cultures, including heterologous. Contamination of cell cultures was performed vaccinated suspension of strain "ARRIAH-DEPT" of coronavirus cattle 8 passage in cell culture MDVK. The research results are summarized in table 1.

Example 3

Obtaining and testing of diagnostic antigens and sera from strain "ARRIAH-DEPT" of coronavirus cattle

To obtain antigen source vaccinated suspension three freeze-thawed. Vaccinated liquid was osvetleni low-speed centrifugation for 30 minutes. Inactivation of viral suspensions were aminoethylethanolamine (AEEI) to a final concentration of 0.1 to 0.15% at 37°C for 24 hours. The resulting preparation was tested for activity and specificity in the DSA. Titles antigens ranged from 6 to 11 log2. Hyperimmunization donors spent emulsion made by mixing the inactivated antigen and mineral or synthetic oils with an appropriate emulsifier.

Rabbits (weight of 2.0-3.0 kg) emulsion of antigen were taken three times: in the crumbs of the hind limbs, in the popliteal lymph nodes and intramuscularly. Cycle immunization was 30-40 days. Table 2 shows the results obtained sera of rabbits in rtga mouse erythrocytes.

The data in table 2 characterize the high antigenic activity of coronavirus cattle from shtam is a "ARRIAH-DEPT", and the resulting diagnostic antigens and serum allow you to diagnose coronavirus infection of cattle.

Example 4

Manufacturing vaccines

To obtain a vaccine against coronavirus infection of cattle inactivated adsorbed macrovu virus seed is obtained from a strain of "ARRIAH-DEPT", stored at -20°With double-thawed-frozen. Transplantable cell culture MDVK with quality monolayer before infection was twice washed from the growth serum with Hanks solution containing trypsin (15-20 µg/cm3). Multiplicity of infection was 0.1 to 1.0 S/cell. After infection, the culture vessels were incubated at 37°C for 1.5-2 hours, occasionally shaking. After contact was made plum vaccinated material and provided support medium containing trypsin (10-15 µg/cm3). The vessels were incubated at 34°37°until JRS more than 90% of the cells. Then the culture was twice frozen-thawed and chilled suspension was osvetleni low-speed centrifugation. Inactivation of viral suspension was performed AEEI at a concentration of 0.1 to 0.15% at 37°C for 24 hours. An inactivated virus was tested for sterility and avirulence. Table 3 summarizes the optimal component composition adsorbed vaccine from strain "ARRIAH-DEPT". Poluchennykh control for sterility and antigenic activity.

Table 4 shows the results of the study in rtga activity of sera of rabbits after administration of inactivated culture vaccine from strain "ARRIAH-DEPT". The data of table 4 demonstrate the immunogenic activity of the inactivated vaccine made from a double harvest of the virus collected at 34°in cell culture MDVK.

Table 5 shows the results of the study activity adsorbed vaccine from strain "ARRIAH-DEPT" on globorotalia cows. The dose is 3 cm3.

The data of table 5 indicate that the titer of antibodies in cows after revaccination increased by 2 log2. As a result of this newborn calves title colostral antibodies was almost 8 log2that is enough to protect them from infection.

Table 6 shows the results of the study activity of the blood sera of rabbits inoculated associated vaccine against Rota - and coronavirus infection of cattle, one component of which is antigenic material from strain "ARRIAH-DEPT" of coronavirus cattle. The data of table 6 show that in the composition of associated vaccine as emulsion and adsorbed antigen of coronavirus from strain "ARRIAH-DEPT also induces the formation of antibodies in high titers.

Thus, the above information indicates the issue is the implementation using the present invention, the following cumulative conditions:

a strain of "ARRIAH-DEPT" of coronavirus cattle, embodying the invention, intended for use in agriculture, namely in veterinary Virology and biotechnology;

for the present invention, it is characterized in the claims, confirmed the possibility of its implementation using the steps described in the application or known before the priority date tools and methods;

a strain of "ARRIAH-DEPT", received in accordance with the invention, has a high antigenic and immunogenic activity and suitable for the manufacture of a vaccine, diagnostic and therapeutic drugs against coronavirus infection of cattle.

Therefore, the present invention meets the condition of patentability "industrial applicability".

Sources of information

1. Syurin NR. et al. Viral diseases of animals. - M, UNITEMP, 1998, 162 to 165, 206-209.

2. Pat. U.S. No. 3919413, 424-89, 11.11.75,

3. Auth. mon. Czechoslovakia No. 249880; a 61 K 39/295, 39/108; 15.03.88,

4. Auth. mon. Czechoslovakia No. 250849; a 61 K 39/295, 39/108; 15.03.88,

5. Auth. mon. Czechoslovakia No. 250850; a 61 K 39/295, 39/108; 15.03.88,

6. Auth. mon. Czechoslovakia No. 1748327; a 61 K 39/00, 39/215; C 12 N 7/00; 10.05.95,

7. Storz, J. et al. Coronavirus isolation from nasal swap samples in cattle with signs of respiratory-tract disease after shipping. Journal of the American veterinary medical Association, 1966. V.208, N9, 1452-1455.

8. WO 98/40097; A 61 K 39/00, 39/215; C 12 N 7/02, 5/10; 17.09.98,

9. Pat. U.S. No. 5916570, 424-222 .1, 29.06.99,

10. Pat. Of the Russian Federation No. 2145236; A 61 K 39/295, 39/108, 39/215, 39/245, 39/12; C 12 N 7/00; 10.02.2000,

11. Pat. U.S. No. 6514502, 424-221 .1, 04.02.03,

3
Table 1
Sensitivity transplantable cell cultures to bovine coronavirus strain "ARRIAH-DEPT"
Cell cultureAccumulation of virus particles/cm3(am)The titer in RSA (log2)
MDVK107,97-10
CRP107,57
Taurus1099-10
Vero107,56-7
Table 2
The activity of the blood serum of rabbits, hyperimmunizing the bovine coronavirus strain "ARRIAH-DEPT"
Series wheyThe antibody titer in RTG
11:321:256
21:321:64-1:128
1:321:64-1:128
Table 3
Optimal component composition (wt.%) vaccines against coronavirus infection inactivated adsorbed from strain "ARRIAH-DEPT"
IngredientsMinimumAverageMax
Antigen507080
AAAI0,10,120,15
GOA49,629,4819,25
10%solution of saponin0,30,40,6

Table 4
Activity of sera of rabbits after administration of inactivated culture vaccine from strain "ARRIAH-DEPT" of coronavirus cattle in RTG
The vaccine is made

from:
no animalThe antibody titers in RTG
1st vaccination2-I in Cinzia
11:161:128
- extracellular21:161:64
hemagglutinin(34°)31:321:64
11:161:128
- total harvest21:161:64
virus (34°)31:321:64
11:81:128
- total harvest21:81:64
virus (37°)31:161:64
Table 5
The study of the antigenic activity of adsorbed vaccine from strain "ARRIAH-DEPT" against coronavirus cattle on globorotalia cows n=16
Feature sera:The antibody titer in rtga in log2(p<0,05)
Globorotalia cows:
- prior to vaccination6,66±0,62
before booster7,75±0,2
after revaccination8,75±0,2
Calves:7,9±0,29
Table 6
The activity of the blood sera of rabbits inoculated associated vaccine
Number of seriesAntigenic components of the vaccineThe form of the vaccineThe average titer of antibodies to coronavirus in rtga (log2)
3Rota - and coronavirusessorbed5,77±0,2
3emulsion6,33±0,11

The strain of coronavirus bovine family Coronaviridae, genus Coronavirus, collection UHF VGNKI "ARRIAH-DEPT", for the manufacture of diagnostic, vaccine and therapeutic products.



 

Same patents:

FIELD: veterinary virology, biotechnology.

SUBSTANCE: invention relates to the strain "K-58" that is deposited in the Collection FGU VGNKI at the registration number '"K-58" № 122 - DEP". The strain is reproduced in 9-11-old SPF-chicken embryos with titer value of biological activity 5.5-7.0 lg EID50/0.2 cm3. The strain is stable and harmless. Its attenuation stability is found in carrying out 5 passages in sensitive chickens. The strain shows high biological, immunogenic and antigenic activities in native state and after inactivation and useful for preparing highly specific and sensitive diagnostics and harmless live and inactivated vaccine preparations.

EFFECT: valuable veterinary properties of strain.

7 tbl, 8 ex

FIELD: veterinary virology, veterinary science, biotechnology.

SUBSTANCE: vaccine comprises antigenic material from the strain "VNIIZZH-DEP" of the cattle infectious rhinotracheitis virus reproduced in transplanted cells culture taken among transplanted cells BHK-21, MDBK and ZKG with the biological activity value at least 6.0 lg TCD50/cm3 and inactivated with aminoethylethyleneimine and also aluminum hydroxide as an adjuvant and, additionally, saponin taken in the effective ratios. The strain is deposited in the collection VGNKI at the registration code "VNIIZZH-DEP". Virus of the strain "VNIIZZH-DEP" is reproduced in transplanted cultures of cells BHK-21, MDBK and ZKG inducing cytopathic effect and virus is accumulated with the titer value 6.5-8.0 lg TCD50/cm3 for 48-96 h. Aminoethylethyleneimine is used in the concentration 0.1-0.2%, aluminum hydroxide is used as 3-4% gel in the amount 19.6-49.6 wt.-% and saponin is used as 10% aqueous solution in the amount 0.4 wt.-%. Vaccine shows high antigenic and immunogenic activity and harmless.

EFFECT: valuable properties of vaccine.

18 cl, 8 tbl, 8 ex

FIELD: biotechnology.

SUBSTANCE: claimed strain is obtained by hybridization of epidemic virus with cold adapted and temperature sensitive virus, which represents attenuation donor and is harmless for adults, and infants of 3-14 years old. Said virus makes it possible to obtain reassortant vaccine strains from new epidemic viruses. Strain is effectively cultivated in germinative hen embryos at 32°C, and has temperature sensitivity and cold adaptation. Reassortant has two genes derived from epidemic virus encoding surface proteins (hemagglutinin and neuroamidinase) and six genes derived from attenuation donor encoding non-glycosilated proteins. Strain has no reactogenicity in relation to adults and infants of 3-14 years old at intranasal application.

EFFECT: strain for living influenza intranasal vaccine with good biological properties and reactogenicity.

3 tbl, 2 ex

FIELD: veterinary virology and biotechnology.

SUBSTANCE: transmissible gastroenteritis of swine virus strain (TGSV) was isolated by sequential passages on SPEV (swine embryo kidney cell) and other cell cultures. Said virus strain is most effectively cultivated in 3-4-day monolayer of SPEV cells, obtained in roll-tube vessel, wherein after cultivation for 24-30 h infective activity level is 7.5 lg TCD50/cm3. Strain survives starting characteristics for 18-month storage and for 9-10 passages (observation time) on SPEV cell culture.

EFFECT: TGSV strain with high biological, antigenic and immunogenic activity useful in production of high-specific and sensitive diagnosticums and high-immunogenic and harmless inactivated vaccine preparations.

7 tbl, 5 ex

FIELD: veterinary virology and biotechnology.

SUBSTANCE: transmissible gastroenteritis of swine virus strain (TGSV) was isolated by sequential passages on SPEV (swine embryo kidney cell) and other cell cultures. Said virus strain is most effectively cultivated in 3-4-day monolayer of SPEV cells, obtained in roll-tube vessel, wherein after cultivation for 24-30 h infective activity level is 7.5 lg TCD50/cm3. Strain survives starting characteristics for 18-month storage and for 9-10 passages (observation time) on SPEV cell culture.

EFFECT: TGSV strain with high biological, antigenic and immunogenic activity useful in production of high-specific and sensitive diagnosticums and high-immunogenic and harmless inactivated vaccine preparations.

7 tbl, 5 ex

FIELD: veterinary virology and biotechnology.

SUBSTANCE: transmissible gastroenteritis of swine virus strain (TGSV) was isolated by sequential passages on SPEV (swine embryo kidney cell) and other cell cultures. Said virus strain is most effectively cultivated in 3-4-day monolayer of SPEV cells, obtained in roll-tube vessel, wherein after cultivation for 24-30 h infective activity level is 7.0-8.0 lg TCD50/cm3. Strain survives starting characteristics for 18-month storage and for 9-10 passages (observation time) on SPEV cell culture.

EFFECT: TGSV strain with high biological, antigenic and immunogenic activity useful in production of high-specific and sensitive diagnosticums and high-immunogenic and harmless inactivated vaccine preparations.

7 tbl, 5 ex

FIELD: virology, veterinary science.

SUBSTANCE: invention proposes a new strain of the avian reovirus ESASS № 99011475 belonging to a new antigen class of avian reoviruses. Also, invention proposes a method for preparing such reoviruses, a vaccine comprising such reovirus, a method for its preparing and a method for control against pathological states in poultries by using such vaccine. Proposed group of inventions provides enhancing the effectiveness of vaccination of poultries against reoviruses. Invention can be used in veterinary.

EFFECT: improved preparing method, valuable properties of strain and vaccine.

9 cl, 6 dwg, 3 tbl, 2 ex

FIELD: veterinary virology and biotechnology.

SUBSTANCE: invention relates to rotavirus strain having high biological, antigenic, and immune activity, as well as dominated properties in relation to epizootic isolates. Claimed virus strain is reproduced in single-layer passed cell cultures wherein after incubation for 24-48 h it accumulates in titer of 5.5-7.5 lg TCD30/cm3. (TCD - tissue cytopathogenic dose). Strain of present invention holds basic biological properties when passing in cell culture.

EFFECT: strain with increased biological, antigenic, and immune activity, inactivation resistance and dominated properties in relation to epizootic isolates.

12 tbl, 5 ex

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 107.0 - 107.5 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

FIELD: medicine, genetic engineering.

SUBSTANCE: invention proposes a method that involves construction of bacteriophage library of random peptides based on oligonuleotide fragments encoding their, selection of bacteriophages binding with target-cells but not binding with cells of other types that can be involves in pathological process or able to show effect on its diagnosis and therapy, and confirmation of specificity of selected bacteriophages by using combination of different tests. Oligonucleotide fragments encoding random peptides are prepared by reaction of reverse transcription by using random primers and total RNAs isolated from indicated target-cells and cells of other types. Applying this invention provides preparing bacteriophages binding with target-cells with high degree of selectivity. Invention can be used in diagnosis, therapy and pharmaceutical industry.

EFFECT: improved preparing method.

3 cl, 2 dwg, 8 ex

FIELD: veterinary virology, biotechnology.

SUBSTANCE: invention relates to the strain "K-58" that is deposited in the Collection FGU VGNKI at the registration number '"K-58" № 122 - DEP". The strain is reproduced in 9-11-old SPF-chicken embryos with titer value of biological activity 5.5-7.0 lg EID50/0.2 cm3. The strain is stable and harmless. Its attenuation stability is found in carrying out 5 passages in sensitive chickens. The strain shows high biological, immunogenic and antigenic activities in native state and after inactivation and useful for preparing highly specific and sensitive diagnostics and harmless live and inactivated vaccine preparations.

EFFECT: valuable veterinary properties of strain.

7 tbl, 8 ex

FIELD: veterinary virology, veterinary science, biotechnology.

SUBSTANCE: vaccine comprises antigenic material from the strain "VNIIZZH-DEP" of the cattle infectious rhinotracheitis virus reproduced in transplanted cells culture taken among transplanted cells BHK-21, MDBK and ZKG with the biological activity value at least 6.0 lg TCD50/cm3 and inactivated with aminoethylethyleneimine and also aluminum hydroxide as an adjuvant and, additionally, saponin taken in the effective ratios. The strain is deposited in the collection VGNKI at the registration code "VNIIZZH-DEP". Virus of the strain "VNIIZZH-DEP" is reproduced in transplanted cultures of cells BHK-21, MDBK and ZKG inducing cytopathic effect and virus is accumulated with the titer value 6.5-8.0 lg TCD50/cm3 for 48-96 h. Aminoethylethyleneimine is used in the concentration 0.1-0.2%, aluminum hydroxide is used as 3-4% gel in the amount 19.6-49.6 wt.-% and saponin is used as 10% aqueous solution in the amount 0.4 wt.-%. Vaccine shows high antigenic and immunogenic activity and harmless.

EFFECT: valuable properties of vaccine.

18 cl, 8 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with treating vestibular and auditory disorders, trigeminal nerve's neuralgia and peripheral paresis of facial nerve of herpetic etiology. The method deals with introduction of an antiherpetic preparation followed by immunomodelling therapy with the use of polyoxidonium. Moreover, after treating with antiherpetic preparation before introducing polyoxidonium it is necessary to conduct additional successive therapy: with preparations of trophic action as milgamma or neuromultivit at simultaneous introduction of antioxidant, then comes intratissue injection of cerebrolysine being behind the top of mastoid process.

EFFECT: the innovation enables to decrease the quantity of relapses due to stopping the development of herpes simplex virus, restore conductivity along nervous fiber and improve endoneural circulation.

3 cl, 3 ex

Medicinal agent // 2268037

FIELD: medicine, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to using 4-chloro-2-methylphenoxyacetic acid of the formula (I)

and its pharmacologically acceptable sodium, potassium and lithium salts (mixture of these salts, or mixture of salts and 4-chloro-2-methylphenoxyacetic acid) as a medicinal agent possessing immunomodulating, anti-inflammatory and antitumor properties, and antiviral activity also. 4-Chloro-2-methylphenoxyacetic acid and its mixtures with pharmacologically acceptable alkaline metal salts possess high effectiveness and enhanced bioavailability.

EFFECT: valuable medicinal properties of medicinal agent.

9 cl, 13 ex

FIELD: chemistry of peptides, medicine.

SUBSTANCE: invention relates to preparing new peptides possessing immunomodulating, anti-proliferative, anti-tumor and antiviral activity. Invention proposes new peptides comprising up to 30 amino acid residues of the general structural formula: X1-Trp-Gly-Gln-X2 wherein X1 is taken among the following group: -His-Gly-Val-Ser-Gly-, -His-Gly-Gly-Gly-, -His-Val-Gly-Gly-, -His-Gly-Gly-Gly-Gly-, and -Gln-Gly-Gly-Gly-Gly, or absent; X2 is taken among the following group: -His-Gly-Thr-His-Gly, -Gly-Gly-Thr-His-Gly, -Pro-His-Val-Gly-Gly, -Pro-His-Gly-Gly-Gly, -Pro-His-Gly-Gly-Gly-Trp-Gly, -Gly-Gly-Gly-Thr-His-Ser, or absent.

EFFECT: valuable medicinal properties of peptides.

8 cl, 5 tbl, 5 dwg, 6 ex

FIELD: organic chemistry, medicine, virology.

SUBSTANCE: invention relates to new derivatives of piperidine of the general formula (II): or their pharmaceutically acceptable salts wherein Xa means -C(R13)2-, -C(R13)(R19)-, -C(O)-, and others; Ra means R6a-phenyl or phenyl substituted with methylsulfonyl; R1 means hydrogen atom or (C1-C6)-alkyl; R2 means R7-, R8-, R9-phenyl wherein R7-, R8 and R9 mean substituted 6-membered heteroaryl and others; R3 means R10-phenyl, pyridyl and others; R4 means hydrogen atom, (C1-C6)-alkyl, fluoro-(C1-C6)-alkyl; R6a means from 1 to 3 substitutes taken among the group involving hydrogen, halogen atom, -CF3 and CF3O-; R7 and R8 mean (C1-C6)-alkyl and others; R9 means R7, hydrogen atom, phenyl and others; R10 means (C1-C6)-alkyl, -NH2 or R12-phenyl wherein R12 means hydrogen atom, (C1-C6)-alkyl and others; R13, R14, R15 and R16 mean hydrogen atom or (C1-C6)-alkyl; R17 and R18 in common with carbon atom to which they are bound form spirane ring comprising from 3 to 6 carbon atoms; R19 means R6-phenyl wherein R6 means R6a or methylsulfonyl; R20, R21 and R22 mean hydrogen atom or (C1-C6)-alkyl; R23 means (C1-C6)-alkyl under condition that if Ra means phenyl substituted with methylsulfonyl then Xa can mean the group only. Compounds of the formula (II) possess properties of CCR5-antagonist and can be used in medicine in treatment of HIV-infection.

EFFECT: improved method for treatment, valuable medicinal properties of compounds and composition.

15 cl, 1 dwg, 12 tbl, 15 ex

FIELD: virology, veterinary science.

SUBSTANCE: invention proposes a new strain of the avian reovirus ESASS № 99011475 belonging to a new antigen class of avian reoviruses. Also, invention proposes a method for preparing such reoviruses, a vaccine comprising such reovirus, a method for its preparing and a method for control against pathological states in poultries by using such vaccine. Proposed group of inventions provides enhancing the effectiveness of vaccination of poultries against reoviruses. Invention can be used in veterinary.

EFFECT: improved preparing method, valuable properties of strain and vaccine.

9 cl, 6 dwg, 3 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: one should perform the following stages: a) removal of contaminants out of plant; b) plant's reducing; c) treatment of reduced plant with laser radiation; d) suspending the mixture obtained at stage c) in water; e) maceration of suspension obtained at stage d) and f) separation of liquid developed. Composition should be obtained due to this technique. It should be applied at treating hepatitis C as an aqueous extract. It should be applied as aqueous extract as immunostimulant. Pharmaceutical preparation includes aqueous extract as an active constituent.

EFFECT: increased biological activity of the product.

43 cl, 16 ex, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new urea-substituted imidazoquinolines of the formula (1):

wherein R, R1, R2 and n have values given in the description, and to pharmaceutical preparations based on these compounds. Proposed compounds possess effect of immunomodulators initiating biosynthesis of different cytokines. Also, invention relates to methods for treatment of different states, among them viral diseases and neoplastic pathologies.

EFFECT: improved method for induction, valuable properties of compounds.

47 cl, 11 tbl, 142 ex

FIELD: pharmaceutics.

SUBSTANCE: the present innovation deals with applying birch bark extract at betulin content in it being above 70% for the purpose to prevent viral hepatitis C and, moreover, manufacture medicinal preparation for preventing viral hepatitis C.

EFFECT: higher efficiency of prophylaxis.

2 cl, 1 tbl

FIELD: veterinary virology.

SUBSTANCE: invention relates to strain with stable infective and antigen activity useful in controlling of immunogenic activity against infective feline peritonitis, as well as in producing of hyperimmune serums and globulins for diagnosis of said disease.

EFFECT: strain with stable infective and antigen activity.

4 ex

Up!