Allergic sensitisation prevention

FIELD: medicine.

SUBSTANCE: invention refers to application of enterovirus in preparing a pharmaceutical composition for prevention or treatment of the diseases associated with IgE-mediated allergic sensitisation and related diseases with using an enteroviral vaccine in which enterovirus does not contain an exogenous nucleotide sequence integrated into a viral genome and coding an allergen causing said allergic sensitisation, and also to a method for prevention or treatment of said diseases.

EFFECT: effective products for treating said diseases.

10 cl, 3 tbl

 

The technical field to which the invention relates.

The present invention relates to reducing the risk of allergic sensitization, particularly sensitization mediated by immunoglobulin E (IgE), and its progression to clinically apparent disease, whereby it is possible to prevent or treat allergic diseases such as asthma, eczema, allergic rhinitis and conjunctivitis. More specifically, the present invention relates to the use of a particular virus in the manufacture of pharmaceutical compositions for the prevention or treatment of diseases associated with allergic sensitization.

The level of technology

Over the past few decades the incidence of allergic diseases is constantly increasing. The immune system is immature in newborns, its development continued during the first months and years of life. In the body of a healthy child is formed in the immune response to pathogenic agents in the environment, but more and more children receive an allergic reaction to harmless external factors, leading to allergic diseases.

Many attempts were made to prevent the development of allergic diseases. For many years it was believed that fully breastfeeding and avoiding contact with possible the sources of allergens (for example, dogs and cats) in early childhood can reduce the risk of allergic diseases. However, the results of such a strategy is unconvincing.

One of the recent assumptions about the causes of allergic disease - the hypothesis about the influence of hygiene ("hygiene" hypothesis), based on the fact that in wealthy countries with high standards of living and hygiene prevalence of allergic diseases is significantly higher than in those countries where conventional less stringent hygiene requirements. In addition, epidemiological studies have noted an inverse relationship between the number of children in the family and allergic diseases [1, 2]. Children growing up in rustic conditions, allergic rhinitis, apparently, is less common [3, 4, 5]. Among urban children, regular contact with Pets are also less common allergic sensitization [4]. The reasons for these relationships are largely unknown, but the "hygiene" hypothesis provides a possible explanation, believing that exposure of the organism to various germs in childhood period of life provides protection against allergic diseases, contributing to the maturation of the immune system [2, 6]. One of the possible approaches to combating allergies consists in the introduction into the organism of probiotics, in particular the lactic acid bacter the th, which, as shown, contribute tolerogen immune response.

In a number of works assumed the role of a Th2-polarized CD4+T cells in the pathogenesis of asthma and allergies [7-9], but the precise mechanisms that control allergic sensitization is unknown. Immune response, polarized Th1-type, can suppress the effects of Th2 cells [7] or regulatory T cells can affect the function of both Th1 and Th2 cells, as well as the balance of Th1/Th2 [8, 9]. Although some messages are contradictory, there is epidemiological evidence that some infections, such as caused by hepatitis A virus (HAV) [10-13], the simplest Toxoplasma gondii [12, 13], the bacterium Helicobacter pylori [12-14] and some bacterial factors [15-17], is associated with reduced risk of allergic diseases, which supports the hypothesis that consider the microbial load is an important environmental factor, we need to create protection against the development of allergies in childhood period of life [18]. Moreover, the UK was found an independent inverse relationship between the number of gastrointestinal infections at the age of 5 years and the risk of atopic diseases [19]. It was also reported that infection with human herpes virus type 6 (HHV-6) in early childhood may protect against the development of IgE-sensitization, atopic diseases and allergies in young children (WO 2006/031195).

About the however, not all microbial infection have a protective effect in the prevention of atopic diseases. For example, it was found that seropositive reaction to such intestinal pathogenic bacteria like Clostridium difficile, Campylobacter jejuni and Yersinia enterocolitica is associated with increased prevalence of atopy among the adult population of Denmark [13]. Recently Benn colleagues reported that infectious diseases in the first 6 months of life (mainly infectious diseases of the upper respiratory tract) increase the risk of atopic diseases [20], and according to the observations of Badger with the risk of atopic diseases increases with the number of airborne viral infections (measles, rubella, mumps, chickenpox) in the age of 1 year [21].

Undoubtedly, there is a need for effective means of reducing the risk of allergic sensitization and thereby prevent and treat related diseases. In particular, it is necessary to prevent the development of allergic diseases such as asthma, eczema, allergic rhinitis and conjunctivitis, food allergic reactions. This meets the needs of the present invention.

Disclosure of inventions

The basis of the present invention is the use of enteroviruses for the prevention or treatment of diseases associated with allergic sensitization. In particular, this invention relates to the use of enterovirus in the manufacture of pharmaceutical is some compositions for the prevention or treatment of diseases, associated with allergic sensitization, and specified enterovirus does not contain exogenous nucleotide sequence is integrated into the viral genome and encoding the allergen that causes the specified allergic sensitization. Also proposes a method of prevention or treatment of diseases associated with allergic sensitization, including the introduction to the patient an effective amount of a pharmaceutical composition, which includes enterovirus, not containing exogenous nucleotide sequence is integrated into the viral genome and encoding the allergen that causes the specified allergic sensitisation.

Specific embodiments are listed in the dependent claims. Other tasks, details and advantages of the present invention made it clear from the following description of the embodiment of the invention.

Brief description of drawings

Figure 1 illustrates the prevalence of allergen-specific IgE in children living in the Karelian Republic of the Russian Federation, according to the data of seropositive reactions to the different serotypes of enteroviruses.

Figure 2 illustrates the induction of FoxP3 mRNA in cultures of peripheral blood mononuclear cells stimulated infectious virus (CBV4); purified enterovirus (CBV4), subjected to heat treatment; different the TLR agonists (poly(I:C), LPS, resiquimod); polyclonal stimulator of T cells (anti-CD3 + anti-CD28). Cells were collected after 24-hour incubation. The results are expressed as relative expression of FoxP3 mRNA compared with cells treated with medium.

Figure 3 illustrates the induction of mRNA of IL-10 in cultures of peripheral blood mononuclear cells stimulated infectious enterovirus (CBV4); purified enterovirus (CBV4), subjected to heat treatment; different TLR agonists (poly(I:C), LPS, resiquimod); polyclonal stimulator of T cells (anti-CD3 + anti-CD28). Cells were collected after 24-hour incubation. The results are expressed as relative mRNA expression of IL-10 in comparison with cells treated with medium.

The implementation of the invention

The basis of the present invention is the discovery that allergic sensitization and related diseases can be prevented by vaccination composition containing as immunoreactive ingredient of enterovirus. Previously on the role of anti-allergic vaccine was proposed (WO 93/11251) recombinant viruses containing the exogenous nucleotide sequence is integrated into the viral genome and encoding the epitope of the allergen and artificial site of proteolytic cleavage; however, the examples that prove the anti-allergic effect, is not cited. This approach radically about the while from those offered by the present invention: in the above publication, the virus acts as a passive carrier or delivery vehicle (vector) for exogenous nucleotide sequence, integrated into the viral genome and encodes the antigen, which is causing a desired immune response against the specified antigen; the present invention is based on the immunoregulatory action caused by enterovirus. Thus, enterovirus used in this invention, an active component and does not contain integrated into its genome an exogenous nucleotide sequence that encodes an allergen, causing allergic sensitization, which is necessary to prevent or arrest. However, enterovirus used in this invention can include non-coding exogenous nucleotide sequence integrated into its genome, as well as coding or non-coding exogenous nucleotide sequence, is not integrated into the viral genome. Enterovirus used in this invention may also include exogenous proteins. In one embodiment of the present invention enterovirus does not contain an exogenous nucleotide sequence encoding exogenous proteins, in particular does not contain integrated exogenous nucleotide sequence encoding exogenous proteins.

The term "allergen" is here called a connection, which may cause an allergic immune response; this may be a whole protein, or W is only his immunoactive fragment, i.e. the epitope. In this regard, the nucleic acids are not considered to be allergens.

The group of enteroviruses includes more than 100 different serotypes. Enteroviral infections usually are subclinical, but can lead to various diseases. About enteroviruses such as poliovirus, Echovirus, Coxsackie virus B and A and enteroviruses, denoted by numerals, it is known that they are involved in the development of various diseases. Enteroviral infections are spread by the fecal-oral route, penetrating into the body of the host through the immune barrier of the mucous membranes and intestines. They are powerful activators of the immune system and cause it substantial changes.

The term "enteroviruses" here includes the whole viral particles, and fragments thereof or combinations thereof. Enterovirus can be represented weakened or not obstructed live viral strain, a genetically modified strain or component originating from enterovirus strain, as, for example, subunit or peptide, a structural protein component or combination of these virus-like particle, a genome or genome fragment (e.g., RNA or cDNA)coding for immunologically active viral protein. Enterovirus can also be killed, i.e. inaktivirovannye strain.

Enteroviruses, especially valuable to prevent the treatment and relief of allergic sensitization, can be identified by their ability to induce immunoregulatory mechanisms or suppress immune responses of Th2 type. Such enteroviruses can be identified by determining their effect on regulatory T cells and/or the balance of Th1/Th2 and/or the formation of cytokines, such as IL-10 during stimulation of peripheral blood leukocytes different enteroviruses in vitro or in vivo in children with enterovirus infections. Typically, these enteroviruses must activate FoxP3-positive regulatory T cells and regulatory cells producing IL-10 or other immunoregulatory cytokines. Such enteroviruses can also reduce the activity of cells of the Th2 type, which is reflected in the decreased production of IL-4 or other cytokines of the Th2 type and/or in parallel to increase the activity of cells of the Th1 type and increase the production of IFN-γ or other cytokines of the Th1 type. Enteroviruses, especially valuable for use in this invention can also be identified in epidemiological studies for their protective effect. Typically, these enteroviruses must meet more often in those individuals who do not develop allergic sensitization or allergic symptoms than those who have allergic sensitization or allergic symptoms. These viruses can be detected by detecting the number is and serotype-specific antibodies in the blood or by analyzing the antigenic and genetic properties of viruses, found in such epidemiological studies.

Weakened (attenyerevan) viruses with reduced virulence. Attenuation of the virus is achieved by various methods, including serial passage of virus in cell cultures; chemical modification of antigenic determinants; construction of recombinant or chimeric viral particles; the induction of mutations in the viral genome, deletions or insertions of certain regions of the genome; selection temperaturecontrolled mutants; the irradiation. Or enteroviruses can be represented weakened natural virus isolates or cDNA or RNA of infectious viruses with reduced ability to cause clinically evident disease.

Live attenuated or not obstructed enteroviruses usually injected into the body through the mouth. Each immunizing dose includes infectious virus or infectious RNA or cDNA concentration (titer)that can cause infection or activation of innate or acquired immunity or to induce regulatory T cells or regulatory cytokines. This dose corresponds to the commonly used dose in the traditional oral live polio vaccine Sabina, including a minimum of 105,5-106TCID50poliovirus type 1, 105TCID50poliovirus type 2, 105,5-105,8TID 50poliovirus type 3 living attenuating strains Sabina. The dose may be different if shown its safety and infectivity or the ability to activate innate or acquired immunity. (TCID - dose, infective tissue culture; TCID50- average cytopathology dose infecting 50% of the cells in culture).

Alternatively, enterovirus according to this invention may include whole viral particles with reduced infectivity or subunit vaccines containing specific antigenic structures of viral proteins or peptides, or combinations thereof (for example, virus-like particles); or fragments of viral RNA or cDNA, encoding the whole virus or individual viral proteins; or inactivated form of the virus. Inactivated vaccines can be obtained by multiplication of the virus in cell cultures, its release from infected cells and culture medium and purification by high-speed centrifugation in density gradient of sucrose or other dense environments. Or clearance of the virus can be chromatographically. The infectivity of purified virions reducing, inactivating them by chemical treatment (for example, inactivation by formalin like used in the production of IPV), irradiation or heat treatment. Subunit vaccines can in order to stand out from purified viral proteins or recombinant viral proteins; synthetic peptides corresponding viral antigenic epitopes; virus-like particles or empty viral shells, which are formed during infection, but do not contain the viral genome. Subunit vaccines are introduced into the organism by themselves or conjugated to haptens or media (for example, particles ISCOM - molecular complexes with immunostimulating properties, chitosan, TLR agonists, biodegradable microparticles).

The above enteroviruses enter into the body parenterally by injection, by mouth, intracutaneously, percutaneously, sublingually, intranasally, by inhalation or through the rectum. Each immunizing dose includes viral patterns in the concentration (titer)that can cause shall immune response. This dose corresponds to the dose used in the case of inactivated polio Salk vaccine, including a 1.8-2 mg viral protein per dose and 20 to 40 D-antigen units of poliovirus type 1,4-8 D-antigen units of poliovirus type 2 and 16-32 D-antigen units of poliovirus type 3. The dose may be different if proven its safety and immunogenicity, or the ability to stimulate innate or acquired immunity, or to induce regulatory T cells or regulatory cytokines. Enteroviruses can be entered in various combinations, including the Aya one or more enterovirus serotypes, administered simultaneously or sequentially. In the case of simultaneous administration of the pharmaceutical composition may be in the form of mixtures of different enteroviruses. Enterovirus can be introduced into the body in combination with at least one allergen, such as whole allergen or an immunological active part to stimulate tolerogen response to the specified allergen. In one of the embodiments of the vaccine according to this invention contains enteroviruses as the only immunoactive ingredient, and in another embodiment it comprises a mixture of enteroviruses and one or more exogenous allergens.

Enterovirus according to this invention is included in a pharmaceutical composition, which in addition to the active ingredients, which immunostimulation may contain pharmaceutically acceptable excipient, media, haptens and adjuvants. Eccipienti, media, haptens and adjuvants may include, for example, phenoxyethylamine alcohol, magnesium chloride, sucrose, thiomersal, formaldehyde, phenol, antibiotics (preservatives) or aluminium salts, polymeric microparticles, ISCOM particles, carrier proteins (e.g., cholera toxin), liposomes, protein molecules (haptens/adjuvants) or TLR agonists.

The pharmaceutical composition according to this invention is administered preferably children under 5 years, more is preferably up to 3 years, particularly preferably up to 2 years, most preferably up to 1 year with subsequent introduction of a booster dose during later life to prevent allergic sensitization. Those sensitization has already occurred, you can obtain the pharmaceutical composition according to this invention at any age regardless of whether symptoms of the disease.

"Effective amount" of the pharmaceutical compositions of the present invention is that amount which can cause congenital or acquired immune response, leading to the development of immunity and protect the body of the recipient from this virus by stimulating the formation of neutralizing antibodies or cellular immune response, or both. An effective amount may be that amount of a composition which is able to cause the formation of regulatory cytokines (such as IL-10), or activate regulatory T-cells (Treg), or to cause a favorable shift in the equilibrium cell Th1/Th2, even if antiviral protective immunity does not arise. Induction of regulatory cytokines or regulatory cells, or shift the balance of Th1/Th2 can occur when the virus-specific or allergen-specific immune response, or both. Perhaps also a more generalized effect on the immune system is, affecting a wide range of immune responses with different antigenic or allergenic specificity. This generalized effect, usually mediated by soluble immunoregulatory cytokines, such as IL-10.

When the immune system encounters an alien components of the environment, including pathogenic agents, immune response occurs, which may dominate the response of type Th1 or Th2. In both cases, the immune response is to fight infection, but Th2 cells also contribute to allergies. For an adequate immune response it is essential that a proper balance of cells Th1/Th2. But people who are prone to allergic diseases, dominates the response to Th2 type. In addition, these people can abnormally functioning regulatory T-cells and other components of the immune regulation.

The term "allergic sensitization" refers to the formation of an immune response dominated by Th2 cells, leading to the formation of allergen-specific IgE against different antigens environment, mostly harmless. Allergen-specific IgE, in turn, mediate hypersensitivity reactions, which cause the symptoms of allergic diseases. This immune response can be assessed by measuring the amount of allergen-specific IgE, for example, in a blood sample. Elevated ur the attention of allergen-specific IgE reflect allergic sensitisation to this allergen. In addition, about allergic sensitization may indicate high total IgE level. For the diagnosis of allergic diseases are also injectable skin tests. The pharmaceutical composition according to this invention, containing enterovirus, is a vaccine that can prevent or stop any disease associated with allergic sensitization.

Mediated by IgE and allergic sensitization can lead to a variety of allergic diseases, including allergic eczema, asthma, IgE-mediated food or drug allergies, allergic rhinitis and allergic conjunctivitis. Enterovirus vaccine according to this invention can reduce the risk of IgE-mediated sensitization and thereby to prevent diseases caused by IgE-sensitization, such as allergic rhinitis and asthma.

Enterovirus vaccine according to this invention to prevent allergic sensitization can get totally all newborns and selected populations, such as children from families in which at least one family member was diagnosed with an allergic reaction or an allergic disease. In addition, enterovirus vaccine according to this invention it is possible to introduce individuals with asymptomatic allergic sensib is essential (elevated levels of allergen-specific IgE in the absence of symptoms) to prevent the development of clinically significant symptoms. Also enterovirus vaccine according to this invention can be used to relieve symptoms of allergic reaction or allergic diseases.

We have studied the variation and Association in the levels of microbial infections and allergic sensitization among children in Finland and the Karelian Republic of the Russian Federation in the course of unique epidemiological studies conducted at two geographically adjacent areas, vary considerably in the socio-economic and cultural relations.

Methods

The object of study

The study involved two cohorts: 266 students living in the Karelian Republic of the Russian Federation, and 266 students living in Finland. These children were presented the main population and were selected regardless of possible allergic or other diseases. All children from the Karelian Republic and the father and mother were Finnish or Karelian ethnicity that created ethnic background, close to that of children from Finland. In each of the cohorts - Russian and Finnish - consisted of 114 boys and 152 girls from the country concerned. The average age of the sample at the time of the study in both cohorts was 11.4 years (range 7-15 years).

Blood samples were taken together in 1988 randomly select which of R students, living in the Karelian Republic. Tracked ethnicity of both parents of each child, and all children whose father and mother were Finnish or Karelian ethnicity, were included in this study (N=266). Each of these 266 children living in the Karelian Republic, Finland had found a pair of - child of the same age and sex, who took a blood sample at the same time of year (not more than 1 month difference)in order to minimize seasonal effect in the effects of germs and allergens on the body. In a Finnish cohort included children, selected according to the same principles as in the Karelian Republic; the original was covered 3654 student living in the province of Oulu (Finland) [23]. Each child were taken blood samples.

Immunoglobulin E and antiviral antibodies

Levels of allergen-specific IgE was measured using the fluorescent enzyme immunoassay UniCAP® (Pharmacia Diagnostics, Uppsala, Sweden). Determined IgE specific to two normal aeroallergens (birch and cat) and for egg albumin, according to the manufacturer's instructions. These allergens were selected because of the contact with them, as you might expect, is quite common in both appearing in the study populations. In the case of allergen-specific IgE were considered positive value of 0.35 IU/l or more. In the earlier paragraph is vodivshihsya research evidence of predisposition to atopy was considered values of total IgE levels above 100 IU/l [24].

Rupprechtii antibodies against enteroviruses were determined using enzyme immunoassay (EIA) and subjected to heat treatment Coxsackie virus B4 (CBV4) as antigen, as described previously [25]. This method detects antibodies that are not specific serotype, but is able to cross-reactions between multiple serotypes enterovirus. The ability of this method to detect cross-reactive antibodies against multiple serotypes increased by heat treatment of viral antigen, which exhibited hidden cross-reactive patterns of the virus.

Antibodies that are specific against this serotype was determined using the neutralization of belascoaran, as described previously [26]. This method allows the quantification of neutralizing antibodies specific for serotype used in the analysis. We have identified antibodies against two serotypes of Coxsackie virus B (CBV4 and CBV5) and two serotypes of echoviruses (ECHO9 and ECHO11), using the reference viral strains of ATSS.

Antibodies of class G (IgG) against hepatitis A virus (HAV) was determined using a commercially available kit for ELISA Enzygnost® Anti HAV according to the manufacturer's instructions (Dade Behring, Marburg, Germany). For further analysis, data processing and calculation of the levels of the antibodies used Behring Elisa Processor III.

Inducts what I immunoregulatory mechanisms

The effect of enteroviruses on immunoregulatory mechanisms investigated by stimulating the enteroviruses cultures of mononuclear cells. Mononuclear cells of peripheral blood taken from healthy laboratory staff, was purified using system BD Vacutainer® CPT™ Tube (BD, Franklin Lakes, NJ, USA) according to manufacturer's instructions. Mononuclear cells were twice washed in RPMI 1640 (Gibco, Invitrogen, Carlsbad, CA, USA) and were cultured for 48 hours at +37°C (5% CO2) in the wells of the culture round-bottom 96-well tablet (Costar 96, Corning Inc., Corning, NY, USA), containing 200,000 cells in 100 μl per well. The culture medium containing human serum (10%), penicillin (1%), streptomycin (1%) and L-glutamine (1%) in RPMI 1640 and one of the following stimulating agents: medium (control); infectious enterovirus (Coxsackie virus B4, 3 plaque-forming units per cell); highly purified and subjected to heat treatment CBV4 concentrations of 1.0 μg/ml; the analogue of double-stranded RNA poly(I:C) (agonist of TLR-3) at a concentration of 5 µg/ml (Alexis Biochemicals, San Diego, CA(USA); resiquimod (agonist TLR7/8) at a concentration of 5 µg/ml (Alexis Biochemicals); lipopolysaccharide (LPS) of E. coli serotype J5 (Rc) as a TLR4 agonist at a concentration of 100 µg/ml (Alexis Biochemicals); a combination of soluble antibodies anti-CD3 and anti-CD28 (R&D Systems, Minneapolis, MN, USA) as a polyclonal activator of T cells.

The impact of the virus on regulatory T-cells was evaluated, op is Adelaja the expression of mRNA FoxP3 and IL-10 using polymerase chain reaction in real time in the system 7900 HT Fast real-time PCR system (Applied Biosystems, Foster City, CA, USA). RNA was isolated using the RNeasy kit Mini Kit according to the manufacturer's instructions. During RNA extraction was carried out by processing Dnazol directly on the columns by means of a set of enzymes RNase-Free DNase has Set (Qiagen, Hilden, Germany). The reverse transcription reaction was performed using revertase M-MLV and buffer solution production Promega (Madison, WI, USA) and random review of the primers. For polymerase chain reaction in real time, designed a special primers for FoxP3 and IL-10, and for binding protein TATA-box (TBP), the primers were published [27] with some modification of the direct primer. Each primer set was one primer that overlaps the boundary between exons. Sequences of primers were as follows: FoxP3 direct 5'-ACA GCA CAT TCC CAG AGT TCC-3', reverse 5'-GAA CTC CAG CTC ATC CAC G-3'; IL-10 direct 5'-CAG TTT TAC CTG GAG GAG GTG-3', reverse 5'-AGA TGC CTT TCT CTT GGA GCT TAT-3'; TBP direct 5'-CGA ATA TAA TCC CAA GCG GTT-3' and reverse 5'-act TCA CAT CAC AGC TCC CC-3'. Synthesized cDNA amplified using a set of DyNAmo Flash SYBR Green qPCR Kit (Finnzymes, Espoo, Finland). Conditions temperature cycle were as follows: 7 min at 95°C, 40 cycles of 10 s at 95°C, 30 s at 60°C and 30 s at 78°C (to eliminate primer dimers), after which the final elongation for 1 min at 60°C. At the end of each PCR stage was added to obtain the melting curve in the temperature range 0°C - 95°C. data analysis the threshold cycle (Ctfor FoxP3 and IL-10 were normalized by the values of Ctfor endogenous control gene TBP. The relative expression was calculated using the method using the system of Pfaff, as described previously [28].

Statistical methods

Statistical analysis was performed using SPSS version 12.0 (SPSS Inc., Chicago, IL, USA) and CIA (Confidence Interval analysis) [29]. The levels of specific IgE, high values (>ME/l) total IgE levels and antimicrobial antibodies in the two paired cohorts were compared using criteria poppy-Namara. Comparison of total IgE levels (continuous variable with an asymmetric distribution) in matched cohorts was performed using sign-rank criterion of Wilcoxon signed. For analysis of associations between antibodies to the virus, high values of total IgE levels and specific IgE in Russia (Karelian Republic) and Finnish (the province of Oulu) cohorts was used to build contingency tables and Chi-square or Fisher's exact test. When analyzing the Association between total IgE levels and specific IgE (klassificirovali as positive or negative) and in the analysis of associations between the levels of IgG against CBV4 and specific IgE was used U-test Mann-Whitney. To determine the independent effect is that each parameter when it was required, was used as a multivariable method logistic regression analysis. Model selection was based on direct step-by-step selection at the threshold of inclusion and exclusion of 0.10. The results confirmed the estimate odds ratios (OR) and 95%confidence intervals (CI). If there were missed or indifferent value, the case is not included in the analysis with these specific parameters. Such cases were few: for example, serological data on microorganisms in children from the Karelian Republic in each of the investigated microorganism could 0-2 missed event. All analyses were two-sided. Are statistically significant value of P<0,05).

Results

The levels of allergen-specific IgE were significantly lower in children than in Finnish (table 1).

The levels of antibodies to enteroviruses and hepatitis A virus were significantly higher in children than in Finnish (table 2). In addition, in the Karelian Republic of the Russian Federation allergic sensitization occurred less often in those children who had antibodies to enteroviruses, while in the case of antibodies to hepatitis A virus such effect was not observed (table 3). Among children with seronegative reaction to enteroviruses in conjunction with 22% had at least one is good result for specific IgE, and among children with seropositive reaction - 5%. In children who have not had specific IgE, the average level of antibodies to enteroviruses was 74 immunoassay unit (IFA) (range 0-224), and those who had at least one allergen-specific IgE, this value was 49 IFE (range 0-154) (P=0,048).

In the Finnish cohort number of children with seropositive reaction to the hepatitis B virus (HAV) was very low (table 2), which complicated the analysis of their Association with allergen-specific IgE. However, antibodies to enteroviruses were detected in Finnish children often, but, in contrast to Russian children, there was no Association with allergen-specific IgE response. (18% of children with seronegative reaction to enteroviruses mentioned at least one positive result in relation to specific IgE, and among children with seropositive reaction such was 23%.)

The fact that the Association between infections and the prevalence of atopy was observed only among Russian children, but not in Finnish, can be explained by assuming that Finnish children are infected at an older age, because the circulation of enteroviruses and other microorganisms in Finland is much smaller. According to the "hygiene" hypothesis is the most important infection in the first months of life, because at this age they have a significant influence on the maturation associated with kishechnikom mechanisms of the immune system, the development of regulatory pathways and the balance of Th1/Th2.

To check whether there is a difference in the protective effect of enteroviruses different serotypes, we examined collectively 244 children living in the Karelian Republic of the Russian Federation on the presence of allergen-specific IgE and neutralizing antibodies against four different serotypes of enteroviruses (CBV4, CBV5, ESNO, ECHO11). Because the level of neutralizing antibodies remain elevated for many years, the presence of these antibodies indicates infection by this serotype in the past that were used in this study. Echovirus 11 (ECHO11) was associated with strong protection against allergic sensitization (figure 1). Among children with seronegative reaction to ECHO11 in conjunction with 31.8 per cent had allergen-specific IgE at least against one of the three allergens listed in table 1; among children with seropositive reaction to ECHO11 such was only 13.2% (P<0,001). According to the results of multiple logistic regression analysis, seropositive reaction to ECHO11 had a clear independent effect on allergen-specific IgE (P<0,001; OR a 3.2 [95% CI 1.7 to 6,2]). These results suggest that the protective effect of enterovirus in relation to allergic sensitization may depend on the serotype.

Protective effect of enteroviruses in relation to allergic CE is civilizacii may be mediated by their effects on the immune system. Usually it is considered that the development of allergic sensitization is associated with abnormal immune regulation. In immune regulation play an important role of regulatory T-cells, and one of the possible mechanisms mediating the anti-allergic effect of the virus, is the virus induced activation of these cells. For regulatory T-cells characterized by the expression of the transcription factor FoxP3 (natural regulatory T cells and the secretion of immunoregulatory cytokines, such as IL-10 (Tr1 regulatory cells). In particular, the secretion of IL-10 by Tr1 cells may be important in suppressing allergic reactions [30]. We investigated whether enteroviruses to stimulate regulatory cells by exposure of peripheral blood mononuclear infectious enterovirus or purified enterovirus subjected to heat treatment in vitro. Induced virus response compared with the response obtained in the case of a TLR agonist (poly(I:C), resiquimod, lipopolysaccharide (LPS) from E. coli) and a polyclonal activator of T cells (a mixture of monoclonal antibodies anti-CD3 and anti-CD8).

Exposure of mononuclear cells with infectious CBV4 has led to a clear increase FoxP3 mRNA expression (figure 2) and IL-10 (figure 3), respectively, 3.3 and 3.6 times compared with the control. Similarly, subjected ceramabryte CBV4 caused increased expression of FoxP3 mRNA in 1.9 times, mRNA of IL-10 in 3-4 times. Poly(I:C) induced mRNA either FoxP3 or IL-10, whereas the combination of antibodies anti-CD3/anti-CD28 increased mRNA expression and FoxP3, and IL-10 (8.1 and 2.6 times, respectively). Resiquimod and LPS did not cause the expression of FoxP3 mRNA (figure 2), but clearly increased the expression of mRNA of IL-10. These results show that enteroviruses can activate regulatory T-cells. Caused by enteroviruses activation comparable with the activation of a powerful polyclonal activator of T-cells with a mixture of antibodies anti-CD3/anti-CD28, which confirms the biological importance of this phenomenon. In addition, enteroviruses able to induce the expression of FoxP3 stronger than the three classical TLR agonist, and the expression of IL-10 is not weaker than the agonists of TLR4 and TLR7/8 (LPS and resiquimod, respectively).

Thus, these results suggest that enterovirus infections are associated with reduced risk of allergic sensitization and may have a modulating effect on the immune system in such a way that stimulated immunoregulatory mechanisms, thereby protecting against allergic disease.

Table 1
Levels of distribution (% and 95%CI) allergen-specific IgE in children of school age in Finland and the Karelian Republic of the Russian Federation for the purpose
Finland (n=266)Karelian Republic (n=266)P
Antigen
Cat11% (8-16%)2% (1-5%)<0,001
Birch11% (8-16%)2% (1-5%)<0,001
Egg6% (4-10%)3% (2-6%)0,093
albumin
At least22% (17-27%)6% (4-10%)<0,001
one positive result
Table 2
Levels of distribution (% and 95%CI) antibodies against enterovirus and hepatitis a virus in children of school age in Finland and the Karelian Republic of the Russian Federation
Finland (n=266)Karelian Republic (n=266)P
Enterovirus77% (72-82%)93% (90-96%)<0,001
Hepatitis A2%* (1-5%)24% (19-29%)<0,001

- On the presence of antibodies against hepatitis a virus were examined 166 Finnish children.

In this study, as enteroviruses antigen used highly purified Coxsackievirus B4, heat treated to achieve broad reactivity with antibodies against different E. torovirus serotypes.

Table 3
The proportion of individuals (% and 95%CI) with a positive reaction to at least one allergen-specific IgE among those with seropositive reaction for antibodies against enterovirus and hepatitis A virus in children of school age residing in the Karelian Republic of the Russian Federation
Seropositive reaction to the virusSeronegativeLogistics
reactionPmodel*
virus
Enterovirus13/2474/18OR (95% CI)P
(5%; 3-9%)(22%; 9-45%)0,020,16
(0,04-0,6)
0,006
Hepatitis A5/63 (8%; 3-17%)12/2010,579NC
(6%; 3-10%)
H3 - insignificant
* Direct step-by-step model (threshold for inclusion/exclusion 0,10)

1. Application of enterovirus in the manufacture of pharmaceutical compositions for the prevention or treatment of diseases associated with IgE-mediated allergic sensitization, and specified enterovirus does not contain exogenous nucleotide sequence is integrated into the viral genome and encoding the allergen that causes the specified allergic sensitisation.

2. The use according to claim 1, in which the pharmaceutical composition according to this invention contains a live strain of enterovirus, a genetically modified strain of enterovirus is, an inactivated strain of enterovirus, structural component, originating from the strain of enterovirus, or their combination, as, for example, virus-like particles.

3. The use according to claim 1, in which the pharmaceutical composition according to this invention contains the genome or genome fragment originating from the strain of enterovirus.

4. The use according to any one of claims 1 to 3, in which the pharmaceutical composition according to this invention is administered into the body through the mouth, intracutaneously, percutaneously, sublingually, intranasally, by inhalation, through the rectum, or by parenteral injection.

5. The use according to claim 1, in which the pharmaceutical composition according to this invention is used to prevent or treat asthma, allergic eczema, food or drug Allergy, allergic rhinitis or conjunctivitis.

6. The use according to claim 1, in which the pharmaceutical composition according to this invention is administered to a child in the first two years of life.

7. The use according to claim 1, in which pharmaceutical compositions containing various serotypes of enteroviruses is administered simultaneously or sequentially.

8. The use according to claim 1, in which the pharmaceutical composition according to this invention is used to prevent allergic symptoms in sensitized individuals or to facilitate allergice the fir symptoms in sensitized individuals.

9. The use according to claim 1, wherein the pharmaceutical composition containing enterovirus, is administered in combination with an allergen.

10. The method of prevention or treatment of diseases associated with allergic sensitization, which requires that the individual is administered an effective amount of a pharmaceutical composition containing enterovirus, and specified enterovirus does not contain exogenous nucleotide sequence is integrated into the viral genome and encoding the allergen that causes the specified allergic sensitization.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: nutritional and pharmaceutical composition in form of baby food contains fat, protein and carbohydrate components and includes milk serum and casein with weight ratio of casein to serum from 1:1 to 1:2.4. They contain, at least: 3 g of arginine per 100 g of protein, from total content of fatty acids: 10 wt % of linoleic acid, 1 wt % of alpha-linoleic acid, one long-chain polyunsaturated fatty acid, selected from group, consisting of docosahexaenic, arachidonic and eicosapentaenoic acid, to 25 wt %, at least one polyunsaturated fatty acid and 2-12 g of indigestible oligosaccharides with polymerisation degree from 2 to 100 per 100 g of dry weight of said composition, as well as neutral and acidic oligosaccharides, containing units of uronic acid. Pharmaceutical composition is applied in treatment and/or prophylaxis of inflammatory disease, diarrhea, eczema and/or atopic dermatitis. Prevention of allergy or diarrhea is performed by introduction of composition to child enterally or perorally.

EFFECT: inventions ensure stimulation of immune system maturing and development in babies of intestine and intestinal flora, similar to flora, obtained during breast feeding, optimal feeding, prevents penetration of allergens into general blood circulation and reduces risks associated with feeding with baby's formula based on milk serum.

17 cl, 4 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine and can be applied for treatment of hyperaemia and edema of mucous membrane of upper airways. For this purpose introduced is loratadine or proper quantity in form of its acceptable salt in combination with phenylephrine or as monomedication. Loratadine is introduced in regimen 2.5 mg four times per day, and phenylephrine is introduced in regimen 8-10 mg four times per day. Loradadine introduction in regimen 2.5 mg per day makes it possible to reach high efficiency of treatment in absence of side reactions.

EFFECT: treatment efficiency by loratadine in combination with phenylephrine in claimed regimen is conditioned by their synergetic effect as well as in absence of side reactions.

28 cl, 3 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to peptides inhibiting mucin hypersecretion. The peptides have an amino acid sequence containing up to 24 amino acid residues of the sequence GAQFSKTAAKGEAAAERPGEAAVA which can have at least one amino acid substitute in said sequence selected from a group consisting of the substitute of A by K, the substitute of F, K, G, Q, S, T and/or E for A; or the substitute of Q for E.

EFFECT: preparation of a pharmaceutical composition on the basis of the peptides for mucin hypersecretion inhibition.

28 cl, 9 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: claimed is application of solid peroral dosing composition of prolonged action, which includes (a) core, containing effective amount of pseudoephedrine or its salt, (b) first envelope, covering core and including swelling in water film-forming neutral or cationogenic copolymer ester, film modifier and lubricating substance, and (c) second envelope, covering first envelope and including effective amount of desloratadine, amount of pseudoephedrine or its salt is sufficient for ensuring maximaum of average geometrical values of pseudoephedrine concentration in plasma, from 345 to 365 ng/ml, for the time from 7.60 to 8.40 h, and amount of desloratadine is sufficient for ensuring maximum of its average geometrical values of concentration in plasma, from 2.10 to 2.45 ng/ml, for period from 4.0 to 4.5 h after intake of single dose of said composition, for preparation of medication for treatment of allergic and/or inflammatory states of upper and lower respiratory ways and skin, or urticaria and nasal and non-nasal symptoms of year-round and seasonal allergic rhinitis.

EFFECT: composition ensures necessary profile of active agents release and is efficient in treatment of allergic bronchospasm, couphing, seasonal allergic rhinites.

3 cl, 4 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a new acid dihydrogenphosphate of 2-(3-{6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidine-4-yl}phenyl)-2-methylpropionic acid of formula optionally in a crystalline form exhibiting cAMP inhibitor properties. Also, the invention refers to a pharmaceutical composition.

EFFECT: compound can find application for treating the diseases associated with cell expression of prostaglandin D2 in such diseases, as allergic rhinitis, bronchial asthma, allergic conjunctivitis, etc.

3 cl, 12 dwg, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to chemical-pharmaceutical industry, namely to creation of medication, which possesses anti-inflammatory and regenerating action. Medication contains the following ingredients: conifer needle extract, purified oleoresin of cedar or pine, or spruce, or fir, or larch or their mixture in equal proportions, vegetable oil.

EFFECT: medication has increased effectiveness and efficiency and also extends arsenal of medications, which have anti-inflammatory and regenerating action.

7 cl, 9 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: in formula (I) Cy1 is a 6-member heterocyclyl containing N as a heteroatom, a 5,6-member monocyclic or 9,10-member bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S and O, phenyl or phenyl condensed with a 5-member heterocycle containing O as a heteroatom, each optionally having 1-3 identical or different substituting Cy1 groups which are: (C1-C6)-acyl, cyano, carboxy, hydroxy, (C1-C6)alkylsulphonyl, (C3-C6)-cycloalkyl, a 6-member heterocyclyl containing 1-2 heteroatoms selected from O and N, phenyl, a 5-member heteroaryl containing 1-3 heteroatoms selected from N, S and O, Y1Y2N-, Y1Y2NC(=O)-, Y1Y2NSO2-, (C1-C6)-alkyl-SO2-N(R5)-C(=O)-, R6-C(=O)-N(R5)-, R7-NH-C(=O)-NH-; (C1-C6)-alkoxycarbonyl; (C1-C6)-alkyl, which optionally contains 1-3 identical or different substitutes which are halogen, carboxy, cyano, hydroxy, Y1Y2N-, Y1Y2N-C(=O)-, R6-C(=O)-N(R5)-, R8-SO2-N(R5)-C(=O)-, 5-member heterocyclyl, containing N as a heteroatom, 5-member heteroaryl containing 1-3 heteroatoms selected from N and O; or (C1-C6)-alkoxycarbonyl; as well as (C1-C6)-alkoxy which optionally have 1-3 identical or different substitutes which are carboxy, (C1-C6)-alkoxycarbonyl, cyano, 3-member heterocyclyl containing O as a heteroatom, or 5-member heteroaryl containing 1-3 heteroatoms selected from N and O; where phenyl or heteroaryl fragments in the substituting Cy1 groups optionally and independently have substitutes represented by hydroxy, (C1-C6)-alkyl, (C1-C6)-alkoxy, carboxy, (C1-C6)-alkoxycarbonyl or R8-SO2-N(R5)-C(=O)-; and where cycloalkyl fragments in the substituting Cy1 groups which optionally and independently have substitutes represented by (C1-C6)-alkoxy, carboxy; Cy2 is a 9-member cycloalkenyl, phenyl, 5,6-member monocyclic or 9,10-member bicyclic heteroaryl containing 1-3 heteratoms selected from N, S and O, or phenyl condensed with a 5,6-member heterocycle containing 1-2 heteroatoms selected from N and O, each independently and optionally having 1-3 identical or different substitutes represented by (C1-C6)-alkoxy, (C1-C3)-alkyl, hydroxy, halogen, halogen-(C1-C6)-alkoxy, nitro, Y1Y2N-; L1 is an alkylene with a straight or branched chain containing 1-6 carbon atoms, optionally substituted carboxy; or L1 is -CH2-(C1-C5)halogenalkylene; L2 is a bond, -O- or -CH2-O-. Other values of radicals are given in the formula of invention.

EFFECT: novel compounds have prostaglandin D2 receptor antagonist properties, can be used in treating primarily allergic disorders such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy and other diseases.

39 cl, 1 tbl, 99 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to application in an effective amount and to new nicotine receptor agonists described by general formula (i) or (ii) for treating inflammatory diseases chosen from a group including asthma, chronic obstructive pulmonary disease (COPD), interstitial pulmonary tissue fibrosis (IPF), sarcoidosis, hypersensitivity pneumonitis (HP), chronic hypersensitivity pneumonitis and bronchiolitis obliterans organising pneumonia (BOOP). The compounds (i) and compounds (ii) relate to formulae (i) (ii) where in formula (i) R1 and R2 independently mean alkyl with 1-10 carbon atoms; Xa means CH or N; Ya means one or more substitutes chosen from hydrogen, halogen, cyano, hydroxyl, alkyl with 1-10 carbon atoms optionally substituted with one or more halogen atoms, and alkoxy with 1-10 carbon atoms; n means an integer 0 or 2; J means a counterion representing a compound for maintaining electric neutrality, e.g., halogen, sulphate, sulphonate; in formula (ii) R3 is chosen from or Xb means N or N+-R10; R4 means one or more substitutes chosen from hydrogen, halogen; each R10, R11 and R12 independently means alkyl with 1-10 carbon atoms; provided the presence of the counterion when Xb means N+-R10.

EFFECT: use of nicotine receptor agonists in the effective amount for treating inflammatory diseases.

26 cl, 40 dwg, 3 tbl, 38 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns cat allergen fused proteins and application thereof. Substance of the invention involves a compositions containing a virus-like particle (VLP) or a viral particle and at least, one antigen, first of all at least, one cat antigen, and more specifically at least one cat antigen which is human allergen. In specific versions of the invention, said antigen represents cat antigen Fel d1 or its fragment covalently bound with the VLP.

EFFECT: invention can be applied for preparing vaccines first of all aimed at treatment and/or prevention of cat dander allergy and other cat antigens and allergens responses.

25 cl, 20 ex, 5 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: daily in morning hours nasal passages are washed with physiological solution, 10% oil solution of vitamin E in dose 3 drops into each passage is dropped into both nasal passages. After 2 hours transcutaneous impact with constant magnetic field and low-intensity laser irradiation with power 30-80 mW, wavelength 0.85-0.89 mcm, pulse repetition rate 50-80 Hz is carried out on region of projection of thymus, maxillary sinuses, submandibular lymph nodes, spinous process of the third cervical vertebra, mastoid process. Time of impact is 60 seconds per each region. Ozonised olive oil is dropped into each nasal passage in dose 3 drops. After that, by means of light-conducting nozzle performed is impact on anterior parts of inferior nasal conchas with pulse red irradiation with wavelength 0.63-0.65 mcm, pulse power of irradiation at outlet not less than 5 W, pulse repetition rate 50-80 Hz, frequency of light diode modulation - 4-8 Hz. Impact time is 60-120 seconds. Total treatment course is 7 days with 4 month interval, 3 times per year. During the first interval between courses bacterial immunomodulator IRS-19 is introduced in age dose in therapeutic regimen. During the second interval antihomotoxic therapy with drugs Luffel and Lymphomyosot is administered.

EFFECT: method makes it possible to increase treatment efficiency, reduce frequency of disease recurrences, reduce medication load in case of allergic rhinites, which usually require long treatment.

2 tbl, 2 ex

FIELD: medicine; veterinary science.

SUBSTANCE: method involves preparation of antigen material from avian influenza virus strain thereafter cleaned from ballast impurity, virus inactivation, mixing of antigen material and oil adjuvant with controlling the end product. The avian influenza virus strain is represented with the strain "Primorsky" of avian influenza virus referred to Orthomyxoviridae family, Influenzae virus avicum type of serotype A, subtype H5N2, collection Federal State Institurion VGNKI, serial №129 - "ДЕП". The vaccine made under the given method, contains cleaned and avirulent antigen material from strain " Primorsky" and oil adjuvant in ratio (wt %): antigen material - 30.0-40.0, oil adjuvant - 60.0-70.0.

EFFECT: decreased labour and power inputs in making the vaccine and improved quality of antigen material, high antigen activity of the vaccine and effective protection of susceptible poultry from epizootic virus of subtype H5.

14 cl, 5 tbl, 6 ex

Immunogenic vaccine // 2333770

FIELD: medicine.

SUBSTANCE: invention concerns medicine, particularly an immunogenic composition capable of activating immune response to poliomyelitis virus. The invention claims an immunogenic composition including deactivated poliomyelitis virus, bacterial polysaccharide or oligosaccharide and stabiliser, in the dried form. After recovery the composition can activate immune response to poliomyelitis virus. The invention also concerns a method for obtaining the claimed composition.

EFFECT: obtaining immunogenic composition capable of activating immune response to poliomyelitis virus and including deactivated poliomyelitis virus.

32 cl, 15 ex, 11 tbl, 2 dwg

FIELD: medicine; veterinary.

SUBSTANCE: method of vaccine obtaining involves virus antigen cultivation in BHK-21 suspension cell culture at the temperature of 36-37°C, purification of virus suspension from ballast admixtures, inactivation, concentration of foot-and-mouth disease virus antigen obtained and combination of antigen concentrate with adjuvant. After 6-8 hours of virus antigen cultivation, percentage of dead cells is registered every 2 hours. When the level of dead cells reaches 95% or more, further cultivation is performed for 2-8 hours depending on the virus type. Foot-and-mouth disease vaccine obtained by this method contains antigen material of a-type and/or O-type and/or Asia-1 type foot-and-mouth disease viruses in effective quantity of 146S-component, aluminium hydroxide gel, saponin and maintenance medium.

EFFECT: increased volume of antigen material during foot-and-mouth disease virus cultivation and obtaining harmless immunogenic vaccine.

13 cl, 1 tbl, 14 ex

FIELD: biotechnology, virology.

SUBSTANCE: claimed strain is obtained by passaging of epizootic isolate on sensitive hetero- and homologous cell cultures. Virus strain is reproduced in sensitive cell cultures and after incubation for 18-24 h 6.0-7.66 lg TCD50/ml is accumulated. In case of mass infection strain takes cytopathic effect over 5 hours, and retains starting characteristics for 10 passages.

EFFECT: strain of high biological, antigenic and immunogenic activity.

1 dwg, 7 tbl, 5 ex

FIELD: veterinary virology, biotechnology.

SUBSTANCE: the suggested vaccine contains avirulent and purified antigenic material out of strain A (Georgia) being homologous to infection agent 1999/N1721-DEP obtained in passaged cell culture VNK-21 being the suspension that contains, predominantly, 146S and 75S immunogenic components of foot-and-mouth disease virus, adjuvants aluminum hydroxide with saponin and maintenance medium in efficient ratios. The vaccine is of high immunogenicity and is capable to provide efficient protection against homologous infection agent circulating in Transcaucasian countries and those of Central Asia, Near and Middle East.

EFFECT: higher efficiency.

10 cl, 1 dwg, 4 ex, 10 tbl

FIELD: veterinary virology, biotechnology.

SUBSTANCE: the suggested vaccine contains avirulent and purified antigenic material out of strain A (Georgia) being homologous to infection agent 1999/N1721 obtained in passaged cell culture VNK-21 being the suspension that contains, predominantly, 146S and 75S immunogenic components of foot-and-mouth disease virus. Moreover, the vaccine contains maintenance medium and butyric adjuvant in efficient ratios. The strain has been deposited in collection of FGU VGNKI under registration number - industrial culture strain of foot-and-mouth disease virus A (Georgia) 1999/N1721-DEP of serotype A. As maintenance medium it is necessary to apply serum-free Earle's solution at addition of FGMS, GBCS and antibiotics at pH being 7.4-7.6. Out of butyric adjuvants the vaccine contains butyric adjuvant of the All-Russia Research Institute of Animal Protection (VNIIZZH) or butyric adjuvant of Montanide ISA-70 or Montanide ISA-260 marks by "Seppic" (France). The vaccine provides efficient protection against homologous infection agent circulating in Transcaucasian countries and those of Central Asia, Near and Middle East.

EFFECT: higher efficiency.

11 cl, 1 dwg, 5 ex, 8 tbl

The invention relates to veterinary Virology and biotechnology

The invention relates to the field of veterinary Virology and biotechnology

The invention relates to veterinary Virology and biotechnology

FIELD: veterinary virology, biotechnology.

SUBSTANCE: the suggested vaccine contains avirulent and purified antigenic material out of strain A (Georgia) being homologous to infection agent 1999/N1721 obtained in passaged cell culture VNK-21 being the suspension that contains, predominantly, 146S and 75S immunogenic components of foot-and-mouth disease virus. Moreover, the vaccine contains maintenance medium and butyric adjuvant in efficient ratios. The strain has been deposited in collection of FGU VGNKI under registration number - industrial culture strain of foot-and-mouth disease virus A (Georgia) 1999/N1721-DEP of serotype A. As maintenance medium it is necessary to apply serum-free Earle's solution at addition of FGMS, GBCS and antibiotics at pH being 7.4-7.6. Out of butyric adjuvants the vaccine contains butyric adjuvant of the All-Russia Research Institute of Animal Protection (VNIIZZH) or butyric adjuvant of Montanide ISA-70 or Montanide ISA-260 marks by "Seppic" (France). The vaccine provides efficient protection against homologous infection agent circulating in Transcaucasian countries and those of Central Asia, Near and Middle East.

EFFECT: higher efficiency.

11 cl, 1 dwg, 5 ex, 8 tbl

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