Method for vaccinal prevention of respiratory diseases in calves

FIELD: medicine.

SUBSTANCE: invention refers to veterinary immunology. A method for the vaccinal prevention of respiratory diseases in calves involves immunising 20-30-day-old clinically healthy calves three times every 10-12 days by subcutaneous injections of animal donor's hyperimmune serum containing anti-parainfluenza virus type 3 hemagglutinin antibodies in titre min. 1:1280, anti-rednose virus hemagglutinin antibodies in titre min. 1:256, anti-viral diarrhoea virus hemagglutinin antibodies in titre min. 1:1024, anti-respiratory syncytial virus hemagglutinin antibodies in titre min. 1:128, anti-rotavirus and anti-coronavirus hemagglutinin antibodies in titre min. 1:128, in a dose of 1 ml/kg of body weight; 15 days after the last injection, the animals are vaccinated by double administration of the inactivated combined vaccine Combovac for rednose, parainfluenza type 3, viral diarrhoea, respiratory syncytial, rota- and coronavirus diseases according to the instructions.

EFFECT: method provides higher postvaccinal immunity and the stimulated antibody production as a result of activating cell and humoral immunity and optimising the natural body resistance.

3 tbl, 2 ex

 

The invention relates to veterinary immunology, relates to a method of immunization, in particular vaccines and can be used for specific protection of calves from mixed respiratory diseases of viral etiology.

The syndrome of acute respiratory viral infections in calves develops when exposed to respiratory viruses, mainly parainfluenza-3, infectious bovine rhinotracheitis, virus diarrhea-diseases of the mucous membranes, respiratory syncytial and adeno, against the background of unfavorable environmental factors. Viral agents are the primary cause of damage to mucous membranes and upper respiratory tract, providing immunosuppressive effect on local immunity in the respiratory tract that promotes penetration into the lungs bacterial microflora, complicating the pathological process. Feature spread of infectious bovine rhinotracheitis virus, viral diarrhea, respiratory syncytial infection is the fact that these pathogens in calves up to 1 month can cause enteritis, in older animals - respiratory disease, and in adults of Mature cows and bulls - impaired reproductive function. In addition, parainfluenza virus-3 is widely distributed in calves older than 1 month of age in violation of the growing technology, i.e., when the stress is inhibiting effects on the body, causing destruction of the respiratory tract. The tropism all the above pathogens can be reproduced in the cells of the respiratory and gastrointestinal tract, reproductive organs, immune cells, i.e. they pantropy. This causes their high contagiousness and severity of the disease.

Gap infectious circuit, and if possible preventing transition of epizootic process in hidden state is considered as the basic principle of combat Anzoategui, one of the main tools which is immunoprophylaxis. Immunoprophylaxis involves the creation of artificial immunity of the body by the introduction of biological agents against the corresponding pathogen, we differentiate between active (using vaccines and anatoxins) and passive (using antibodies in serum or globulin) immunization.

Known methods of prophylaxis of viral respiratory disease of calves using monovalent (live and inactivated) or polyvalent vaccines /1/. Known methods of immunization are based on complex events, including intranasal inoculation of calves during the first weeks of life, their booster (parenteral) in 3-4 months and vaccinated cows /2/. Vaccination of calves provides them with protection from infection 10-14 is it (using live vaccines) or 21 days (when using inactivated) after repeated administration of vaccine /3/.

The preferred analog is considered the way of specific prophylaxis of infectious diseases of cattle with the use of inactivated combination vaccine "Combopack against infectious bovine rhinotracheitis, parainfluenza-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronavirus disease, which is injected calves at the age of 30 days twice with an interval of 20-25 days /4/.

On the effectiveness of vaccination negatively affected by the presence of calves colostral antibodies that block the antigens injected vaccines, thereby blocking the formation of immunity and exacerbating infectious process. In addition, vaccines can cause post-vaccination reactions (reactogenicity and allergenicity of vaccines), decreasing during a certain period of time (1-10 days) quality of animal health, and their use is almost always accompanied by a temporary (7-14 days) immunodeficiency body condition of the animals. The use of live or inactivated vaccines do not prevent latency virulent viruses in animals.

The purpose of the invention is to improve the prevention of mass respiratory disease of calves viral etiology.

This goal is achieved by a combination of passive (using hyperimmune serum donor animals) and active (when the label inactivated vaccine) immunization according to the original schema.

The method is as follows.

Clinically healthy calves 20-30 days of age subjected to immunization three times with an interval of 10-12 days of subcutaneous injection of hyperimmune serum donor animals containing antihemagglutinin to parainfluenza virus-3 (titre not less than 1:1280), infectious bovine rhinotracheitis virus (titer 1:256), viral diarrhea virus-diseases of the mucous membranes (titer 1:1024), respiratory sindicalismo virus (titer 1:128), rotavirus and coronavirus (titer 1:128)at a dose of 1 ml/kg body weight and 15 days after the last injection Vaccinium twice the introduction of inactivated combination vaccine "Combopack against infectious bovine rhinotracheitis, parainfluenza-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronavirus diseases, with an interval of 21 days in doses according to the instruction.

Effective prevention of respiratory disease of calves polyetiological nature was determined in the research-and-production experiments in conditions of households, long prone to respiratory diseases due to exposure to associations of viruses, pathogenic and conditionally pathogenic microflora in the background of violations of conditions and feeding pregnant cows and calves. Virological studies confirmed etiologic role of viruses Annex the PAP-3, infectious bovine rhinotracheitis, virus diarrhea-diseases of the mucous membranes, respiratory syncytial virus, Rota - and coronaviruses. Hyperimmune serum was prepared according to the method of N. And. Gorban (1981) from the blood of clinically healthy adult donor animals live weight of not less than 300 kg of the same economy, free from infectious and blood parasite diseases.

The essence of the method is illustrated by examples.

Example 1. In terms of the economy, long prone to viral diseases of calves occurring as a mixed infection caused by the virus of infectious bovine rhinotracheitis, parainfluenza-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronaviruses (incidence - 80,0%, mortality - 20%), according to the principle analogues formed three groups of clinically healthy calves 20 days old. Calves of the first group were immunized three times with an interval of 10 days of subcutaneous injection of hyperimmune serum donor animals containing antihemagglutinin to parainfluenza virus-3 (titre not less than 1:1280), infectious bovine rhinotracheitis virus (titer 1:256), viral diarrhea virus-diseases of the mucous membranes (titer 1:1024), respiratory syncytial virus (titer 1:128), rotavirus and coronavirus (titer 1:128)at a dose of 1 ml/kg body weight; calves of the second group were immunized twice with an interval of 21 days injection and inactivated combination vaccine "Combopack against infectious bovine rhinotracheitis, parainfluenza-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronavirus diseases, calves third group were immunized three times with an interval of 10 days of subcutaneous injection of hyperimmune serum donor animals containing antihemagglutinin to parainfluenza virus-3 (titre not less than 1:1280), infectious bovine rhinotracheitis virus (titer 1:256), viral diarrhea virus-diseases of the mucous membranes (titer 1:1024), respiratory syncytial virus (titer 1:128), rotavirus and coronavirus (titer 1:128)at a dose of 1 ml/kg body weight, and 15 days after the last injection - twice with an interval of 21 days injections of inactivated combination vaccine "Combopack against infectious bovine rhinotracheitis, parainfluenza-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronavirus diseases. The animals were clinical observation, recorded the number of infected animals and the nature of the disease. The observation period of 3 months. The results are presented in table 1.

Table 1
The main clinical characteristics of calves
IndicatorsGroups of animals
1st group: hyperimmune serum donor animals*2nd group: the vaccine "Combopack"group 3: hyperimmune serum donor animals*+vaccine "Combopack"
The number of animals that goal.101010
Sick goal. (%):4 (40,0)3 (30,0)1 (10,0)
viral gastrointestinal illness (GCB)321
viral respiratory disease (RB)11
Form parabolani:
- lightweight1 (GCB)2 (GCB)1
- heavy2 (JCB, RB)1 (RB)
Palo, goal (%)2 1-
Safety, %80,090,0100,0
Average daily gain in live weight, g516,2±16,5528,0±18,6748,0±20,1
*Hyperimmune serum donor animals containing antihemagglutinin to parainfluenza virus-3 (titre not less than 1:1280), infectious bovine rhinotracheitis virus (titer 1:256), viral diarrhea virus-diseases of the mucous membranes (titer 1:1024), respiratory syncytial virus (titer 1:128), rotavirus and coronavirus (titer 1:128).

As can be seen from table 1, the viral disease was registered in all groups, and respiratory pathology in the 1-St and 2-nd groups proceeded in severe (group 1 - 2 cases, 2 group - 1 case). Calves were treated in traditional ways with symptomatic funds, including antibacterial. Full recovery was not achieved, and the animals were forced to killed. Immunization with hyperimmune serum with subsequent vaccination not only reduced the incidence and provided parabolani in the form of light, but also contributed to a better development of the calves, which was confirmed by the increase in cf is destockage increase in live weight on 232,0 g in comparison with the 1st group and 220,0 g compared with the 2nd group.

Example 2. In terms of the economy, long prone to viral diseases of calves occurring as a mixed infection caused by the virus of infectious bovine rhinotracheitis, parainfluenza-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronaviruses (incidence - 60,0%, mortality - 10%), according to the principle analogues formed two groups of clinically healthy calves 30 days of age. Calves of the first group were immunized three times with an interval of 10 days of subcutaneous injection of hyperimmune serum donor animals containing antihemagglutinin to parainfluenza virus-3 (titre not less than 1:1280), infectious bovine rhinotracheitis virus (titer 1:256), viral diarrhea virus-diseases of the mucous membranes (titer 1:1024), respiratory syncytial virus (titer 1:128), rotavirus and coronavirus (titer 1:128)at a dose of 1 ml/kg body weight, and 15 days after the last injections, twice with an interval of 21 days injections of inactivated combination vaccine "Combopack against infectious bovine rhinotracheitis, parainfluenza-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronavirus diseases. Calves of the second group were immunized twice with an interval of 21 days injections of inactivated combination vaccine "Combopack against infectious bovine rhinotracheitis, paragi the PA-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronavirus diseases. The effectiveness of prevention was assessed by the following indicators: relative and absolute content of T - and b-lymphocytes (defined in the reaction spontaneous rosethorne method N. And. Blinova, 1980), functional activity of neutrophils blood was determined in the reduction reaction of nitrocine of tetrazole (NBT-test) according to the method M. Wixman and A. M. Mayan, 1979), the level of immunoglobulins specific isotypes (G, M) (determined by the method Manchini, 1964), the authors estimated the effect activity of blood serum (determined by the method of O. I. Smirnova, and T. A. Kuzmina, 1966), the level of neutralizing antibodies to parainfluenza virus-3, infectious bovine rhinotracheitis, virus diarrhea-diseases of the mucous membranes, respiratory syncytial virus and Rota - and coronavirus (determined in response inhibition of haemagglutination reaction of indirect haemagglutination assays and enzyme-linked immunosorbent assay). Blood samples for immunobiological studies conducted prior to vaccination, 21 days after vaccination and 21 days after revaccination. Take into account the results of clinical observations (number of diseased animals, the average daily gain in live weight, safety).

The results are presented in tables 2 and 3.

Table 2
Immuno-biological indicators calves
IndicatorsGroups of animals
1st group: hyperimmune serum donor animals + vaccine "Combopack"2nd group: the vaccine "Combopack"
prior to vaccination21 days after vaccination21 days after revaccinationprior to vaccination21 days after vaccination21 days after revaccination
T-lymphocytes, %24,7±1,026,8±0,931,0±0,8***22,3±1,023,8±0,526,0±0,6
T-lymphocytes, 109/l1,8±0,11,5±0,082,1±0,2***1,5±0,11,5±0,081,8±0,2
B-lymphocytes, %7,5±0,28,2±0,4 8,4±0,3*7,4±0,58,3±0,48,9±0,3
B-lymphocytes, 109/l0,5±0,040,5±0,040,6±0,01**0,5±0,040,5±0,040,6±0,01*
The functional activity of blood neutrophils, %:
spontaneous test7,6±0,3of 8.0±0.48,6±0,3***7,4±0,37,1±0,47,8±0,3
- induced test25,2±0,830,4±0,836,6±0,7***23,3±0,726,4±0,728,6±0,5
Immunoglobulins (mg/ml
G17,6±0,419,8±0,624,0±0,3***17,9±0,519,0±0,322,5±0,4
M1,1±0,091,6±0,051,8±0,03***1,0±0,061,1±0,051,3±0,05
The authors estimated the effect activity of blood serum, %2,4±0,022,8±0,13,2±0,08***2,2±0,052,5±0,093,0±0,1
The titer of neutralizing antibodies to the virus HPT-3, log21,1±0,44,8±0,27,2±0,3***1,1±0,44,2±0,36,4±0,4
The titer of neutralizing antibodies to AI virus-3, log21,9±0,56,6±0,28,0±0,2**1,9±0,75,9±0,27,0±0,2
The titer of neutralizing antibodies to the virus VD-BS, log22,0±0,46,4±0,310,2±0,2***1,8±0,45,8±0,058,2±0,2
The titer of neutralizing antibodies to the virus PC, log21,2±0,66,2±0,37,2±0,7***1,2±0,85,9±0,46,4±0,2
The titer of neutralizing antibodies to rotavirus, log22,0±0,46,8±0,29,4±0,2***1,8±0,46,0±0,28,0±0,3
The titer of neutralizing antibodies to coronavirus, log21,9±0,36,0±0,48,2±0,4***1,7±0,45,7±0,26,7±0,2
* p<0,05; ** p<0,02; *** p<0,01; **** p<0,001.

Table 3
The results of clinical observations
IndicatorsGroups of calves
Experienced, n=15Control, n=15
Hyperimmune serum donor animals+vaccine "Combopack"Vaccine "Combopack"
Ill, goal., (%)1 (6,7)3 (20,0)
Form parabolani goal.:
- lightweight11
- heavy02
Palo, goal., (%)01 (6,7)
Prophylactic efficacy, %93,380,0
Average daily gain in live weight, g648,0±20,1528,0±18,6
The safety goal., (%)10090,0

As can be seen from the table , vaccination of calves resulted in the formation of an immune response, and the calves of the first group of tension was higher than in calves of the second group, which was reflected in a statistically significant increase of antibodies to all viruses. The maximum content of antibodies to all viruses were recorded 21 days after revaccination, it exceeded the corresponding figures prior to vaccination: the titer of neutralizing antibodies to the virus of infectious bovine rhinotracheitis 6.5 times (group 1) and 5.8 times (the second group); parainfluenza virus-3 - 4.2 times (the first group) and 3.7 times (the second group); the viral diarrhea virus-diseases of the mucous - 5.1 times (the first group) and 4.6 times (the second group); respiratory syncytial virus - 6 times (the first group) and 5.3 times (the second group); rotavirus - 4.7 times (the first group) and 4.4 times (the second group); coronavirus - 4.3 times (the first group) and 3.9 times (the second group). Vaccination in the first group was conducted against a background of higher indicators of immune status, testified to better adapt to adverse environmental factors and contributed to the drafting of the immune system to generate an adequate response. A high level of specific immunity in calves of the first group provided prophylactic efficacy at the level of 93.3% (compared with 80% in the second group) and the safety - on is equal to 100.0% (compared with 90.0% of the second group). The sick calf of the first group of respiratory infection was spent in a mild form, and after a course of drug therapy, complete recovery was observed after 8 days. 2 calves from 3 patients in the second group of respiratory infection was spent in heavy, 1 calf - in the form of light. After a course of drug therapy has 1 calf with severe parabolani full recovery occurred after 14 days, the calf with a mild form of parabolani - 10 days. 1 calf fell.

Studies have shown that the claimed method was ensured by the increase in post-vaccination immunity and stimulation of the production of antibodies in the activation of cellular and humoral immunity and optimization of natural resistance of the organism.

Sources of information

1. Urban, B. N., Naiman, I. L. Diseases of young animals in the cattle industry. - M.: Kolos, 1984. - S. 192-196.

2. Infectious diseases of animals. Directory./Comp. Y. F. B., L. C. Kirillov; Ed. by D. F., Osize. - M.: Agropromizdat, 1987. - S. 99.

3. Efanova L. I. Protective mechanisms of the body. Immunodiagnostics and immunoprophylaxis of infectious diseases of animals. - Voronezh: the VSAU, 2004. - 391 S.

4. EN 2395298 C1, 2010.

Method of vaccination respiratory disease of calves, including immunization clinically healthy calves twice the introduction inactive the bathtub combination vaccine "Combopack against infectious bovine rhinotracheitis, parainfluenza-3, viral diarrhea is a disease of the mucous membranes, respiratory syncytial, Rota - and coronavirus diseases, characterized in that the calves 20-30 days of age subjected to immunization three times with an interval of 10-12 days of subcutaneous injection of hyperimmune serum donor animals containing antihemagglutinin to parainfluenza virus-3 in titre not less than 1:1280, the virus of infectious bovine rhinotracheitis in titer of 1:256, viral diarrhea virus-diseases of the mucous membranes in the titer of 1:1024, respiratory sindicalismo the virus titer of 1:128, rotavirus and coronavirus in titer of 1:128, at a dose of 1 ml/kg body weight, and vaccination is carried out 15 days after the last injection.



 

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3 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I), wherein A means morpholinyl, 1,4-oxazepamyl, piperidinyl, pyrrolidinyl or azetidinyl which is bound to N; R1 means C1-C6-alkyl group; R2 means bicyclic aryl group specified in 1H-indolyl, 1H-pyrrolo[3,2-b]pyridyl, quinolyl, naphthyl, 1H-pyrrolo[2,3-b]pyridyl, 5H-pyrrolo[3,2-d]pyrimidinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, benzo[b]thiophenyl, imidazo[1,2-a]pyridyl, benzo[b]thiazolyl, 5H-pyrrolol[2,3-b]pyrazinyl and quinoxalinyl which can be substituted by R4; R3 means hydrogen or halogen atom; R4 means C1-C6-alkyl group, C1-C6-halogenalkyl group, OR1A, halogen, -(CH2)aOH, CN, NHCOR1A, SO2R1A or NHSO2R1A; R5 means C1-C6-alkyl group, -(CH2)aOH, -(CH2)aOR1B, halogen or CONH2; provided p is a plural number, R5 can be identical or different, or R5 can be combined with another R5; each of R1A and R1B independently means C1-C6-alkyl group; a is equal to 0, 1 or 2; n is equal to 1 or 2; p is equal to 0, 1, 2, 3, 4 or 5. Besides, the invention refers to intermediate compounds of formulas (IA) and (IB) for preparing the compounds of formula (I), to a preventive or therapeutic agent containing the compounds of formula (I), pharmaceutical compositions, using the compounds of formula (I) and to a method for preventing or treating diseases.

EFFECT: compounds of formula (I) as selective 5-HT2B receptor antagonists.

11 cl, 1 dwg, 18 tbl, 88 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, particularly to therapy, and concerns treating acute and chronic respiratory diseases and cough syndrome. That is ensured by administering a pharmaceutical composition containing activated potentiated antibodies to bradykinin, morphine and histamine.

EFFECT: invention provides the pronounced effect in infectious-inflammatory and allergic cough by the synergetic effect of the ingredients of the composition.

4 cl, 4 ex, 2 dwg, 5 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound representing 4-methylbenzene sulphonate 6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-N-{[5-(methylsulphonyl)pyridin-2-yl]methyl}-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide, and to its new crystalline form. The invention also refers to a method for preparing the above compound and to a pharmaceutical composition, for treating a disease or a condition wherein inhibition of neutrophilic elastase activity with the above compound and/or crystalline form is considered to be effective.

EFFECT: what is prepared is the new compound and its crystalline form which can find application in medicine for treating an inflammatory disease or condition, such as COPD (chronic obstructive pulmonary disease).

15 cl, 8 dwg, 10 tbl, 16 ex

FIELD: veterinary medicine.

SUBSTANCE: as plant drug raw material the aboveground part of elfwort is taken and infusion is prepared from it. The infusion is administered orally at a dose of 1 ml/kg of live body weight during the first two weeks of life of piglets.

EFFECT: method is highly effective for prevention of mass gastrointestinal and respiratory diseases of suckling pigs, it promotes to general tonic action of biologically active substances of plant origin on the body of suckling pigs, increase in weight gain, ensuring reduction of the adaptation period.

2 cl, 3 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: treating respiratory distress syndrome accompanying neonatal ventilation is ensured by measuring glutathione peroxidase (GSH-Px-3) with underlying drug therapy, and the measured value being less than 2.41 mcmole/l requires including intravenous bolus injections of the preparation Selenase in a therapeutic complex at 10 mcg/kg/day, once a day for 10 days.

EFFECT: method provides increasing the survival rate in reducing a number of complications and a length of treatment by ensuring a lower severity of oxidative stress and a higher antioxidant protection of the body.

1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology and medicine, and concerns an vaccine against influenza caused by known viral strains of influenza A and B, as well as potential reassortants. The presented polyvalent influenza vaccine is based on a hybrid protein containing N1, N3 and N5 protein fragments of influenza A virus, a haemagglutinin fragment of influenza B virus and FliC1 and FliC2 flagellin components (SEQ ID NO:1) bridged flexibly. The protein-coding nucleotide sequence (SEQ ID NO:2) is optimised for the high expression in Escherichia coli cells.

EFFECT: using the characterised vaccine enables providing the general protection against influenza.

3 cl, 4 dwg, 1 tbl, 13 ex

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