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Method for vaccination efficacy increasing against bacterial and viral infections

Method for vaccination efficacy increasing against bacterial and viral infections
IPC classes for russian patent Method for vaccination efficacy increasing against bacterial and viral infections (RU 2342174):
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Strain of lactobacilli lactobacillus paracasei cncm i-2116 (ncc 2461) eliciting ability to prevent intestine colonization with pathogenic microorganisms causing diarrhea, supernatant of its culture and oral agent for prophylaxis and/or treatment of diarrhea-associated disorders Strain of lactobacilli lactobacillus paracasei cncm i-2116 (ncc 2461) eliciting ability to prevent intestine colonization with pathogenic microorganisms causing diarrhea, supernatant of its culture and oral agent for prophylaxis and/or treatment of diarrhea-associated disorders / 2243779
Invention relates to the strain Lactobacillus paracasei CNCM I-2116 used for diarrhea prophylaxis causing by pathogenic microorganisms. Supernatant of this strain culture elicits ability to prevent colonization of intestine with pathogenic microorganisms causing diarrhea also and this strain is designated for preparing agent used for prophylaxis and/or treatment of disorders associated with diarrhea. Agent for oral administration represents therapeutically effective dose of the strain L. paracasei CNCM I-2116 or supernatant of its culture and acceptable foodstuff. Invention provides the enhanced viability of the strain in its applying and effectiveness in prophylaxis of adhesion to intestine cells and invasion to intestine cells of pathogenic microorganisms causing diarrhea.

FIELD: medicine; epidemiology.

SUBSTANCE: probiotic drug Vitaflor is administered during 10 days before, on the day of, and 10 days after the vaccination. Before the vaccination Vitaflor is administered perorally as lactobacillus fermented milk, and intranasally as water solution. On the day of, and after the vaccination Vitaflor is administered sublingually as tablets. The invention allows vaccination efficacy increasing due to raising affinity and avidity of antibodies, formed after the vaccination, their prolonged circulation in serum, as well as raising functional activity of phagocytes.

EFFECT: vaccination efficacy increasing.

5 tbl, 1 ex, 2 dwg

 

The invention relates to medicine, namely to the epidemiology and prevention of infectious diseases of bacterial and viral etiology, and can be used to improve the effectiveness of vaccines in the prevention of acute respiratory infections, pneumonia and other nosological forms of diseases.

A known way of increasing the effectiveness of vaccination against bacterial and viral infections in organized groups, including the additional introduction of immunomodulatory drugs, which are used ribomunyl or IRS-19 (EN 2223783 C1, 20.02.2004).

The purpose of the invention is the extension of prophylaxis of diseases, in particular, in organized groups.

The aim is achieved in that for the prevention of disease using drugs for immunization, and appoint probiotic Vilaflor oral, intranasal and sublingual.

The method is implemented as follows. For prevention of morbidity prescribed drugs for immunization and appoint probiotic Vilaflor oral, intranasal and sublingual.

The essence of the method lies in the fact that probiotic as immunobiotics is a universal non-specific preparation of patients for vaccination in two stages.

Phase I - during the 10 days the th in the human body, be inhaled or injectable vaccination, introduced probiotic Vilaflor per os (oral) on an empty stomach before meals three times a day (morning, afternoon and evening) of 150.0 ml in the form of fermented milk lactobacilli (the so-called acidophilus milk in the form of thick yogurt, sour cream or type of yogurt) containing Lactobacillus 5-8×108CFU/ml in the logarithmic growth phase. During these first 10 days (twice daily, morning and evening) patients received Vilaflor and in the form of nose drops, prepared ex tempore by adding 3.0 ml of water in industrial output standard penicillin vial with two doses of powdered freeze-dried Vilaflor with the content of lactobacilli 2×108CFU/ml, followed by shaking the vial, closed with a stopper, to dissolve the lyophilisate. In each of the bow was buried on 5 drops (each drop - 0.05 ml) dissolved in water Vilaflor 2 times a day, every day administered in two doses contributed 10 drops (0.5 ml lactobacilli strain formulas Vilaflor, respectively, 1×108SOME L.acidophilus) course 10 days (dose rate of 10×108SOME places).

The next day after a completed course of 10-day probiotic oral and intranasal prevaccine preparation stage II - vaccination at a known regulated CX is IU in combination with a triple before a meal on an empty stomach daily for the next 10 days sublingual use tablets Vilaflor, containing two standardized dose 2×108CFU/ml of freeze-dried lactic acid bacteria strain formula Vilaflor. Before the subsequent vaccination in the vaccination calendar, patients undergo a similar two-step course prevaccine preparation of oral ingestion of the probiotic in combination with intranasal instillation of Vilaflor (stage I) and combined with vaccination sublingual use of pelletized forms of Vilaflor (stage II).

In our studies, patients separately or successively vacciniavirus flu vaccine"Grippol" or "Vaxigrip") and pneumococcal polysaccharide vaccine Pneumo 23", when before vaccination (phase I) three times daily for 10 days received per os no of 150.0 ml of a fermented milk product Vilaflor and also twice intranasal solution of probiotic Vilaflor in full compliance with the above 2-stage scheme, and then (II) immunotherapies vaccine in combination with daily over the next 10 days (three on an empty stomach before eating) receiving the probiotic Vilaflor under the tongue in the form of a special sublingual tablets containing two standardized dose 2×108CFU/ml of freeze-dried Vilaflor.

Schematically the inventive method of optimizing the process of vaccination are presented in table 1.

Table 1
The sequence of processes vaccination claimed and known methods
The inventive method There is a method of vaccination
I stage. Pradakshina preparing a probiotic Vilaflor 10 days: per os three times a day of 150.0 ml intranasally twice a day for 1×108KOE
Immunization
Stage II. Immunization in combination with the 10-day sublingual pills of Vilaflor 2×l08KOE three times a day

The analysis in 2004-2005 comprehensive research results the following tables No. 1-4 showed that the proposed method, in contrast to conventional immunization schemes without affecting probiotic, allows you to:

1. To hold non-specific probiotic preparation mucosal immune system of the human body to the subsequent perception and to respond adequately to the introduction of bacterial and/or viral antigens by normalizing immunomodulatory and regulatory impacts through dendritic cells of the mucous MALT (mucosal immune system of the person, Mucos Assotiated Lymphoid Tissue)aimed at establishing a protective resistance to the insertion of vaccine antigens in the human extentof bacterial and/or viral etiology.

2. To initiate a programmable sequence of activation of the immune system to get stronger specific immune response in cellular and humoral immunity without accompanying side effects at the organism level as possible fever, muscle or joint pain, aches, nonspecific fever and loss of normal activity, labor or combat effectiveness, exacerbation of chronic disease and other

3. To enhance the readiness of the patient to Th1, Th2 type immune (but not allergic) response by increasing the overall readiness of the organism to the introduction of foreign antigens, and therefore to improve the functional readiness of macrophages, macrophages, antigen presenting cells and other echelons of the immune system, mucous membranes. Thus, the possibility is directed to generate an optimal path activation of immunity for mass days of vaccination of large numbers of people, directly and indirectly, to adapt the immunogenicity of influenza and pneumococcal vaccines, to prolong their protective action to increase the safety and overall effectiveness of such drugs.

4. To increase nonspecific resistance of members of organized groups in the period of forced close contact and adaptation to new conditions is under intensive physical, emotional and stress loads.

5. Significantly reduce the share of the carriage of the major causative agents of acute respiratory infections, laryngitis, tracheitis, bronchitis and pneumonia in the structure of pathogenic and conditionally pathogenic microflora bacterial, mycoplasmal, chlamydiales and viral nature. Thus, the decrease in the carriage at the Protocol was registered for Streptococcus pneumoniae pneumococcal - in is 1.81-1.83 times; Staphylococcus aureus Staphylococcus aureus - 1,84-2,14 times; Haemophilus influenzae Haemophilus influenzae in 8,58-at 10.64 time; mycoplasmas Mycoplazma pneumoniae - 1.3-1.5 times; chlamydia Chlamydia pneumoniae - 1.2-1.4 times; influenza viruses, parainfluenza, adeno-, RS -, and coronaviruses - 1.3-1.6 times.

6. Directly and indirectly, to reduce the incidence of pneumonia and acute respiratory infections 2.2-3.5 times, which corresponds to 220-350% efficiency in comparison with the control groups due to non-specific local and systemic antagonistic effects on major pathogens and stimulate the immune system.

7. To facilitate and reduce the severity of the clinical manifestations and course of diseases pneumonia and respiratory infections in case of their development on one or two orders of magnitude, to reduce the number of developing complications associated with exacerbation of or layered with other diseases, to reduce the number of bed-days and to accelerate the process of rehabilitation of patients and their return to active the th accomplishing training or combat missions.

A case study on the effectiveness of the proposed method according to the developed scheme.

Study of the effectiveness of influenza and pneumococcal vaccines together with probiotic "Picaflor" for prevention of pneumonia and acute respiratory infections was conducted in three groups of young people aged 18-20 years total number of 425 (table 2).

Table 2
The scheme measures by group
No. of groups Number Prophylactic
"Picaflor" "Grippol" Pneumo 23"
Group # 1 145 + + -
Group # 2 114 + + +
Group # 3 (comparison) 166 - + -
Just people. 425 259 425 114

145 group 1 in the first 10 days of arrival received probiotic "Picaflor" in the form of a lactic acid product by one of the ice cream dish 3 times a day, and in the form of nose drops, prepared by adding in a bottle with dry subliminal the authorized product 3 ml of water and shaking the container, the closed tube, to dissolve the lyophilisate. In each of the bow was buried on 5 drops diluted in water "Picaflor" 2 times a day. The next day was administered influenza vaccine Grippol and at the same time under the tongue gave preformed mold release "Picaflor" (1 sublingual tablet 3 times a day).

114 group 2 also received "Picaflor" on a similar scheme and were also vaccinated with Grippol. In addition, influenza vaccine behalf of the 2nd group were vaccinated with pneumococcal vaccine Pneumo 23".

3rd group (comparison group) consisted of 166 people, not receiving "Picaflor", but vaccinated "Grippol".

317 people from all 3 groups were dynamically repeatedly surveyed bacteriological, virological and immunological methods at different times after arrival.

Table 3
The influence of "Picaflor" on the reduction of the share of the carriage of bacterial pathogens and viral nature
View of the activator The proportion of carriers of pathogens in the examined groups(%%) The advantages of the proposed method (tuple)
No. 1 "Grippol" with "Vitafoam" No. 2 "the Flu is l" + Pneumo 23" with "Vitafoam" No. 3 "Grippol" without "Picaflor" No. 3/No. 1 No. 3/No. 2
S.pneumoniae 16,6 16,4 30,0 1,81 1,83
N. influenzae 3,1 2,5 26,6 8,58 at 10.64
S.aureus 9,0 10,5 19,3 2,14 1,84
M.pneumoniae 6,4 5,5 8,3 1,3 1,5
Creemore 1,6 1,4 1,9 1,2 1,4
viruses 1,6 1,3 2,1 1,3 1,6

As is obvious from table 3, it was found that the proportion of speakers of all major pathogens: pneumococcal, Haemophilus influenzae, Staphylococcus aureus, Mycoplasma, chlamydia and viruses (adeno-, RS-, corona-, parainfluenza and other) in groups # 1 and # 2, where he took "Vilaflor was significantly less than among personnel in the comparison group (group # 3), where "Picaflor" was not applied. Thus, the proportion of carriers of pneumococci in the first and second groups was less than 1.8 times, Haemophilus influenzae, respectively 8.6 and 10.6 times, Staphylococcus aureus - 2.1 and 1.8 times, M.pneumoniae 1.3 and 1.5 times, Creemore - the 1.2 and 1.4 times, viruses (adeno-, RS-, corona-, parainfluenza and other) 1.3 and 1.6 times than the respective comparison groups (see table 2).

The results of a comparative study of the effectiveness of means of prevention of pneumonia and acute infections of the respiratory tract in organized groups are presented in table 4.

The incidence of pneumonia among receiving Vilaflor for 10 days and inoculated with influenza vaccine, but not vaccinated with Pneumo 23" (group # 1) was 1.8 times lower (P<0,01)than in the comparison group, the personnel of which was inoculated with influenza vaccine, but did not receive Vilaflor (table 3).

The incidence of pneumonia among grafted Grippol and Pneumo 23", as well as receiving Vilaflor (group # 2) was 2.9 times lower than in the comparison group (P<0,001).

The incidence of acute respiratory infections and acute bronchitis in groups # 1 and # 2 was 2.5-4.1 times lower than in the comparison group (P<0,001).

The incidence of angina in groups # 1 and # 2 was 1.5-1.6 times lower than in the comparison group (P<0,01).

Table 4
The effectiveness of the prevention of pneumonia and acute infections of the respiratory tract
Nosological form The incidence in groups, promille And the code efficiency
No. 1 (Vilaflor + Grippol) No. 2 (Vilaflor + Grippol + Pneumo 23) No. 3 (Grippol) - comparison group Only No. 3/No. 1 No. 3/No. 2
Pneumonia 69,0 43,9 126,5 84,7 1,8 2,9
Abrehet 48,3 35,1 144,6 82,4 3,0 4,1
ARD 131,0 79,0 325,3 192,9 2,5 4,1
Angina of 31.4 33,9 54,2 47,1 1,5 1,6

In the study of paired sera obtained before the introduction of influenza and pneumococcal vaccines and 1-2 months after vaccination, it was found that among persons vaccinated influenza vaccine and receiving "Picaflor", increase the GTS antibodies to influenza a was greater than among persons vaccinated influenza vaccine not received "Picaflor", and among persons vaccinated with pneumococcal vaccine and receiving "Picaflor", increase the GTS pneumococcal antibodies was higher than among those not vaccinated with pneumococcal vaccine not received "Picaflor" (1, 2).

However, it should be noted that, with the Asha point of view, the use of probiotic Vilaflor by the present method in comparison with the known significantly improve resistance and protectionist of the organism to infectious and inflammatory diseases is not due to a quantitative increase of specific antibodies, and due to:

1. Increase epinasty and the avidity produced after vaccination of specific antibodies IgM, IgG and IgA classes.

2. More prolonged blood circulation developed antibodies.

3. Stimulation of functional properties of completion of phagocytosis by phagocytes and their predecessors - by neutrophils from all of the granulocytic series systemically in the blood and topically to mucous membranes, bronchi and alveoli.

4. Suppression not only infectious inflammation, but inflammation and immune and all components of the allergic components of the first, third, and fourth types immunoallergic reactions.

Thus, it was found that under the action of Vilaflor an increase in local and systemic nonspecific and specific resistance of the organism.

Table 5
Comparative characteristics of the severity of the clinical course of pneumonia in vaccinated individuals receiving and not receiving Vilaflor
The number of cases
Not received Vilaflor Received Vilaflor
Abs. % Abs %
Form clinical course light 11 52,4 5 88,3
average 9 42,8 1 16,7
heavy 1 4,8 0 0
Complications, including pleurisy 3 14,3 0 0
1 4,8 0 0
The average number of trumpeter 25,2 a 21.5

If grafted "Grippol" and "Pneumo 23" became ill with pneumonia, the disease treated "Picaflor" flowed easier than among the non-treated "Picaflor" (table 5). The proportion of mild forms of pneumonia among them was 1.7 times higher than in the control group. It is characteristic that among treated Vilaflor was completely absent severe forms of pneumonia and no complications in the form of a fatal outcome of the disease, the Yaya disease duration was 3.7 days shorter than in the comparison group vaccinated with the same vaccine, but without the probiotic Vilaflor.

Thus, it is obvious that the inventive method probiotic preparation patients in the exhaust worker doses and courses Vilaflor can significantly improve the efficacy of vaccination against bacterial (for example, pneumococcal vaccine) and viral (for example, influenza vaccine) infections in all standard methods of research on the effectiveness of processes vaccination.

The way to increase the effectiveness of vaccination against bacterial and viral infections by injection for immunization and additional infusion of immune-modulating means, wherein such use probiotic Vilaflor, which is injected prior to vaccination for 10 days orally 3 times a day for 150 ml in the form of fermented milk with lactic acid bacteria content of lactobacilli 5-8·108CFU/ml, and administered 2 times a day 5 drops in aqueous solution with a content of lactobacilli 1·108CFU/ml; at day of vaccination and for the next 10 days to introduce Vilaflor sublingually 3 times a day in pill form with the content of lactobacilli 2·108CFU/ml

 

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