[Cost-effectiveness of pneumococcal vaccination among patients with chronic heart failure].

Aim      To analyze the cost-effectiveness of pneumococcal vaccination in 40- and 65-year-old patients with chronic heart failure (CHF).Material and methods  Analysis was performed by Markov modeling from the perspective of the healthcare system. The evaluation was based on Russian epidemiological data taking into account results of international studies. The analyzed schedule of vaccination included one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent polysaccharide vaccine (PPSV23) after one year and vaccination with only one dose of PCV13. The time horizon of the study was 5 years. Costs and life expectancy were discounted at 3.5% per year.Results The cost-effectiveness of vaccination for both 65-year-old and 40-year-old CHF patients is very high: the incremental cost of one additional QALY (Quality-Adjusted Life Year) for PCV13+PPSV23 vaccination is 113.24 thousand rubles, while vaccination with PCV13 entails a reduction in costs by 556.50 rubles per one vaccinated patient. For vaccination of 40-year-old CHF patients with PCV13+PPSV23, the incremental costs per 1 QALY will be 519.72 thousand rubles, while for vaccination with PCV13 it will be 99.33 thousand rubles.Conclusion      Pneumococcal vaccination of CHF patients reduces the associated morbidity and mortality and is highly cost effective.

[Hydrogen effect on the mechanisms of mucosal immunity in patients with COVID-19].

AIM: To study the inhalation of an active form of hydrogen effect to mucosal and system immunity in a rehabilitation program for health workers. MATERIALS AND METHODS: The study involved patients that survived COVID-19 after therapy with inhaled hydrogen for 90 minutes (n=30), and a control group of patients treated according to standard protocol for managing patients that survived COVID-19 during the rehabilitation period (n=30). Biomaterial was carried out in 2 stages: on the first day of the study, before the accepted therapy and on the 10th day of the study. The indicators of humoral and cellular immunity were studied. The levels of secretory immunoglobulin A (sIgA) and IgG were investigated using the method of enzyme-linked immunosorbent assay. Phagocytosis was assessed on a Beckman Coulter FC-500 flow cytometer. Statistical data processing was carried out in the GraphPad Prism 7.00 software using nonparametric methods. RESULTS: It was shown that the phagocytic index (PI) of monocytes in nasal scrapings after inhaled hydrogen treatment did not significantly change relative to the first day of treatment and control, while the PI of granulocytes in nasal scrapings significantly increased relative to the first day by 2.5 times (p=0.000189), as well as relative to the control by 1.1 times (p=0.047410). PI of monocytes in pharyngeal scrapings showed a significant increase relative to the first day of treatment by 2.8 times (p=0.041103), however, did not differ relative to the control. PI of granulocytes of pharyngeal scraping did not differ significantly relative to the first day and control. PI of granulocytes and blood monocytes of the studied group did not change significantly. PI of granulocytes and monocytes of peripheral blood relative to control during therapy did not change. The sIgA level in nasal scrapings significantly increased by 2.9 times, while in pharyngeal scrapings the level of sIgA significantly decreased by 2 times. Сonclusion. We have shown an increase in granulocytes PI in the nasal cavity and oral monocytes, as well as in the level of sIgA in the nasal cavity during therapy with active hydrogen. The data obtained indicate the effectiveness of therapy, which can be used both in the treatment of COVID-19, and in post-COVID syndrome as an additional therapy. The absence of changes in blood parameters, as well as individual links in nasal and pharyngeal scrapings, requires further study to develop ways to overcome treatment tolerance.

[Biological activity of interferons in the novel coronavirus infection COVID-19].

INTRODUCTION: The immunopathogenesis of the novel coronavirus infection COVID-19 is usually associated with the development of imbalance in the immune response to its causative agent, SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). This is manifested, in particular, by interferons' (IFNs) deficiency at the beginning of the disease followed by hyperproduction of pro-inflammatory cytokines. The virus causes a decrease in IFN types I (α/ß) and III (λ) levels; changes in IFN type II (γ) are less studied. In this regard, it is relevant to assess the functional bioactive IFN (interferon status) in COVID-19. The aim of the study was to assess the antiviral potential of the body by testing the biologically active IFNs in COVID-19. MATERIAL AND METHODS: We used biological serum samples of COVID-19 patients taken in the acute phase (110 patients on the 1-5 days of the disease) and during rehabilitation (47 patients during 1-3 months after the disease onset). Assessment of interferon status was performed according to the technique developed by the authors and described earlier. RESULTS: The IFN status of patients with COVID-19 in the acute period and in the phase of post-infection rehabilitation was studied вduring the observation period. It was found that SARS-CoV-2 causes a pronounced inhibition of biological activity of IFN types I and II compared to the reference values by more than 20 and 7 times, respectively. During the post-COVID period, incomplete recovery of the IFN system activity was registered, which proceeded very slowly. No cases of reaching physiological indicators of interferon status were identified during the observation period. CONCLUSION: The obtained data on deficiency of the functional biologically active IFN confirm the hypothesis about the predominant role of impaired IFN production of different types in the immunopathogenesis of the novel coronavirus infection.

[Comparison of measles incidence in different age groups with the intensity of specific humoral immunity in healthcare workers in Moscow].

INTRODUCTION: The study of the intensity of humoral immunity to the measles virus (Paramyxoviridae: Morbillivirus) (MV) remains relevant due to the ongoing registration of the cluster cases of measles (including nosocomial cases).The aim of the study was to analyze correlation between the intensity of the humoral immunity to measles virus and the measles incidence in different age groups of the Moscow residents. MATERIAL AND METHODS: A simple analytic study was carried out under the framework of measles prevention improvement program conducted in the subjects of the Russian Federation. The study included the analysis of the reasons for the increase in the proportion of seronegative individuals and the comparison of the results of seromonitoring with the data of age-related measles incidence. Throughout 2018, total 1,855 blood serum samples obtained from employees of a large hospital center in Moscow who were previously vaccinated against measles were tested for IgG antibodies (ABs) to MV. The subjects were divided into 11 groups according to their age. Statistical analysis of the obtained data was performed using nonparametric criteria. RESULTS AND DISCUSSION: The proportion of seronegative individuals among the staff of the medical facility decreased with age, from 38.5% in persons aged 19-23 to 0% among employees aged 64 and over. Persons aged 19-43 years were the most susceptible to measles infection, which was confirmed also by the highest incidence rate at these age groups (from 6.93 to 14.03 per 100,000 population). The age group most protected against measles was those over 64 years of age, who were all seropositive and had the lowest rates of incidence. This is probably due to the fact that by this age most of them have had a measles infection and have formed a sufficient immune response. At the same time, younger individuals living in the post-elimination era have only vaccine-induced ABs to MV, the level of which declines rapidly to non-protective values in the absence of boosterization due to the exposure to the wild-type strain of the pathogen. CONCLUSION: The monitoring of the MV-specific IgG- AB levels is required for employees in the medical institutions under the age of 35. Administration of the single dose of the appropriate vaccine is recommended for seronegative individuals.

[Possible mechanisms of impaired post-vaccination immune response in obesity].

Obese people are at high risk of developing infections, including COVID-19, and are prone to a more severe course and a poorer prognosis of diseases. The review summarizes information on the post-vaccination immune response in obesity in children and adults with infections. The SARS-COV-2 pandemic further exacerbates this problem of the adequacy of the immune response to vaccination of obese people. The purpose of this review is to present and summarize information on the changes in various links of cellular and humoral immunity in the experiment and in the clinic during the immune response to vaccination in obesity. Results. The mechanisms of action of obesity and associated chronic inflammation and metabolic dysregulation on the post-vaccination immune response in various infections are discussed. The systemic inflammatory response that occurs in obesity represents a barrier to the induction of a sustained immune response. In obese individuals, innate and adaptive immune responses are slowed down and diminished, contributing to the spread of infections. Conclusion. In obesity, the differentiation and proliferation of cells of the immune system is impaired, and the immune response to vaccination changes. Further research is needed to study post-vaccination immunity in obesity, taking into account the effect on the vaccination of the microbiota of a particular person, the presence of possible comorbid conditions.

[Intensity of the immunity against measles in employees of the maternity unit in Moscow].

INTRODUCTION: Measles remains an urgent problem in Russian healthcare. Despite the ongoing vaccination, there is an increase in the incidence of measles. Prevention of measles is particularly important in high-risk groups, as well as among healthcare professionals to prevent hospital-acquired outbreaks of infection. The duration of post-vaccination immunity during the elimination of measles has not been sufficiently studied, so often people who  have had measles in childhood or have 1-2 vaccinations against the disease lose their protective antibodies with age in the absence of natural boosterization.Goals and objectives. To study the intensity of specific immunity to measles in employees of the maternity unit. MATERIAL AND METHODS: The study involved 271 employees of the maternity unit aged 21 to 93 years (262 serum samples). The level of IgG antibodies (Ab) to the measles virus in the blood serum was studied by ELISA using a standard set of reagents for the quantitative determination of IgG by «VECTOR-BEST¼. The result was  considered negative if the concentration of IgG to the measles virus in tested sample was ≤ 0.18 IU/ml and  positive - if > 0.18 IU/ml. Results. The number of seronegatives ranged from 0% to 30.8% in female employees with its maximum at age of 31-35 years. The lowest proportion of seronegative and the highest proportion of seropositive women were observed among the elderly, > 60 years. DISCUSSION: There is a marked tendency for an increase of the proportion of persons with average Ab levels with age and a decrease of the proportion of persons with low Ab levels. The percentage of seronegative women among employees exceeded the recommended level, which makes it possible for an nosocomial outbreak when an infection is introduced. CONCLUSION: The authors recommend that serological testing for the intensity of the immune response against measles should be included in the standard of the pre-vaccination screening for adults.

Application of bacterial therapeutic vaccine Immunovac-VP4 in the treatment of pollinosis.

AIM: The aim of the study was to study the effectiveness of the complex use of bacterial therapeutic vaccine Immunovac-VP4 and allergen-specific immune therapy (ASIT) in pollinosis in children and adults. MATERIALS AND METHODS: Bacterial therapeutic vaccine Immunovac-VP4 was used annually, nasal and oral administration in patients before the course of ASIT standardized aqueous-salt solutions of allergens. RESULTS: The therapeutic application of bacterial vaccines, Immunoac-ВП4 before the course ASIT has helped to reduce the frequency of acute respiratory infections in 8,5 times in comparison with the control group. Clinical efficacy of complex treatment according to the results of the survey of patients in 7 years after the start of therapy was 90%. There was a significant decrease In IgG4 to causally significant allergens, General immnunoglobulin E (IgE) and a tendency to decrease IgE. CONCLUSION: The use of bacterial therapeutic vaccine Immunovac-VP4, which is a natural ligand of toll-like receptors in combination with ASIT, seems to be an effective and promising direction in the treatment of allergic diseases.

[Analysis of the effectiveness and long-term results of formation of adaptive immunity in the use of various medications and vaccination schemes against pneumococcal infection in patients with chronic obstructive pulmonary disease]. / Analiz otdalennykh rezul'tatov éffektivnosti i formirovaniia adaptivnogo immuniteta pri primenenii raznykh preparatov i skhem vaktsinatsii protiv pnevmokokkovoi infektsii u bol'nykh s khronicheskoi obstruktivnoi bolezn'iu legkikh.

AIM: To assess the long-term clinical results of vaccination with pneumococcal polysaccharide and conjugated polysaccharide vaccines in the separate and sequential use, by determining the optimal vaccination schedule in adult patients with chronic obstructive pulmonary disease (COPD) and to investigate adaptive immunity levels. SUBJECTS AND METHODS: The clinical effects of vaccination were evaluated in patients with COPD within 1 and 4 years after immunization against pneumococcal infection using various schemes, as well as the time course of changes in adaptive immunity indicators was examined. RESULTS: Four years after vaccination, the 13-valent pneumococcal conjugate vaccine (PCV13)/23-valent pneumococcal polysaccharide vaccine (PPV23) group showed a decline in the number of patients with COPD exacerbations by 50% (p<0.001) and reductions in the number of antimicrobial chemotherapy cycles by 47.8% (p<0.001) and in that of hospitalizations by 87.5% (p<0.001). At 1 year after vaccination versus at baseline, the COPD patients vaccinated against pneumococcal disease, regardless of the drug and schedule of vaccination, displayed elevated levels of IgG antibodies to the mixture of capsular polysaccharides included in PPV23 and PCV13. CONCLUSION: It has been indicated that a complex of basic therapy for patients with COPD should include initial vaccination with PCV13, followed by administration of a booster dose of PPV23.

[INDUCTION OF EFFECTORS OF INNATE AND ADAPTIVE IMMUNITY IN THE PROCESS OF THERAPY OF TOPIC FORM OF RECOMBINANT INTERFERON- α2b DURING RESPIRATORY INFECTIONS IN PREGNANT].

AIM: Study immunologic phenotype of lymphocytes in the process of therapy of topic form of recombinant interferon-α2b during respiratory infections in pregnant. MATERIALS AND METHODS: 74 pregnant women from 14 weeks of gestation took part in the study, among them 55 - within 24 hours with symptoms of acute respiratory infection (ARI) of light and me- dium, severe course of infection, who do not need hospitalization. Group I - 34 pregnant womenwithARI receivingbasic therapywith human recombinant interferon-(α2b in gelform. Group II - 21 pregnant with ARI receiving only basic therapy. Control group had 19 pregnant women without signs of ARI. Relative content of principle lymphocyte subpopulations was studied by flow cytofluorimetry: CD3+, CD3+CD4+, CD3+CD8+, CD3-CD19+, CD3- CD16+56+, CD3-CD8+; immune regulatory indexwas calculated inblood within 24 hours from the onset of the disease and 8 - 10 days later. RESULTS: A disbalance of lymphocyte sub- populations was noted in pregnant women with light or medium severity course of acute respiratory infections, that was characterized by an increased content of CD3-CD16+56+ and CD3+CD8+, as well as a reduced content of CD3+ and CD3+CD8+. Inclusion of a topical form of recombinant interferon-α2b during the first days of development ofthe disease has a systemic effect on cell immunity and results in normalization of subpopulation compo- sition of blood lymphocytes that is characteristic for physiological course of pregnancy. CONCLUSION: Administration of topic form of recombinant interferon in pregnant with light or medium severity of ARI can be accompanied by activation of factors of innate and adaptive immunity.

[Choice of optimal vaccination tactics against pneumococcal infection from immunological and clinical standpoints in patients with chronic obstructive pulmonary disease].

AIM: To provide a rationale for choosing the optimal tactics of vaccination against pneumococcal infection in patients with chronic obstructive pulmonary disease (COPD) in the context of evidence-based medicine and on the basis of immunological and clinical data. SUBJECTS AND METHODS: Patients with COPD were examined during a year after vaccination with a 13-valent pneumococcal conjugate (Prevenar-13, PCV13) and a 23-valent pneumococcal polysaccharide (Pnemo-23, PPV23) vaccines. The following vaccination schemes were used: PCV13 monovaccination, PPV23 monovaccination, sequential vaccination with PPV23/PCV13, and sequential vaccination with PCV13/PPV23. RESULTS: Vaccination using all the analyzed schemes in the patients with COPD caused a statistically significant reduction in the frequency of exacerbations, the number of antibiotic cycles, and the number of hospital admissions, as shown by the results of analysis of short-term data. The use of PCV13 was followed by additional effects that were unobserved in the use of PPV23, namely: it promoted the formation of immunological memory to Streptococcus pneumoniae antigens, resulted in the enhanced activity of nonspecific resistance factors, and caused activation of antiviral defense factors. CONCLUSION: If patients with COPD need to be vaccinated against pneumococcal infection, preference should be given to PCV13 monovaccination. Short-term observations have shown that the sequential use of pneumococcal conjugate and polysaccharide vaccines is redundant and gives no additional benefit to patients with COPD. However, the sequential application of both vaccines may have additional advantages in the long term.

[EFFECT OF INFLUENZA VACCINES ON SUBPOPULATIONS OF BLOOD DENDRITIC CELLS].

AIM: Study the effect of Vaxigrip split, Influvac subunit and Grippol plus immune-adjuvanted vaccines on the content of myeloid (mDC) and plasmacytoid (pDC) dendritic cells (DC) in blood of vaccinated healthy women. Materials andmethods. Blood of 30 healthy women aged 18-50 years was studied at days 7 and 30 after the vaccination. pDC (CD14+CD16-/CD85k(ILT3)-PE/ CD123-PC5) and mDC (CD14+CD-16-/CD85k(ILT3)-PE/CD33 -PC5) immune phenotyping was carried out using mAbs (Beckman Coulter, France) and flow cytometer Cytomix FC-500 (Beckman Coulter, USA). RESULTS: Use of unadjuvanted vaccines Vaxigrip and Influvac resulted in an increase of the numbers of mDC and pDC (p<0.05) in blood of the vaccinated only at day 7 of the observation. Grippol resulted in a more significant (2.2 - 3.6 times, p<0.05) increase of DC subpopulations (compared with unadjuvanted vaccines) at both day 7 and a month after the vaccination. CONCLUSION: Influenza vaccination activated innate effectors - the first component on the way of infection penetration - dendritic cells of both myeloid and lymphoid origin. Wherein, a more pronounced and prolonged effect of such activation is observed when immune-adjuvanted vaccine is used compared with subunit and split vaccines.

[IS A THIRD DOSE OF MEASLES VACCINE NECESSARY - AN IMMUNOLOGIST'S VIEW].

Immunological aspects of features of post-vaccine immune response to measles virus are presented and causal relationships are detected, that lead to the disappearance of protective anti- bodies against measles virus, as one of the arguments for improvement of vaccination tactics with the aim to increase immune population and enhancement of epidemiologic situation regarding measles in general. At contemporary stage during mass vaccinations against measles a portion of seronegatives among women of reproductive age and newborns (up to 20.1%) with an additional increase of this parameter by 8 - 13% during pathologic course of pregnancy is established. At the age of 12 months portion of seronegatives among children with health deviations reaches 80 - 90.0% against 53.8% - in healthy. Revaccination of children with deviation of health is shown not to result in production of antibodies against measles virus at protective titers in 30.4 - 33.3% of cases, that could facilitate formation of risk groups for measles virus infection during unfavo- rable epidemic situations. A problem of possible introduction of a third dose of the measles vaccine. among the indicated population groups is discussed.

[Anogenital warts: a new way of solving the common problem of urology (results of long-term follow-up)].

AIM: To evaluate the effectiveness of combined use of the imiquimod 5% cream and vaccination against human papillomavirus (HPV) using a quadrivalent recombinant vaccine to achieve long-term clinical remission of chronic HPV infection manifested by anogenital warts. MATERIAL AND METHODS: The study comprised 36 patients, including 22 men, aged 26.4+/-4.1 years, who had from 1 to 5 anogenital warts. Participants of the study were vaccinated by quadrivalent recombinant vaccine under a 3-dose scheme 0-2-6 months co-administered with imiquimod 5% cream three times per week up to 16 weeks. The follow-up period was 2 years. RESULTS: Complete disappearance of genital warts within 1 year from baseline was observed in 34 (94.4%) patients. Two patients with anogenital warts after 1 year were treated for 1 year 3 months and 1 year and 4 months with Solcoderm which lead to the complete disappearance of genital warts. There were no recurrences of genital warts during the 2 years of follow-up. CONCLUSION: Vaccination with a recombinant quadrivalent vaccine concurrently with using imiquimod 5% cream results in prolonged clinical remission of chronic HPV infection manifested by anogenital warts in at least 94.4% of the cases (2 year follow-up).

[COMPARATIVE ACTIVITY OF INFLUENZA VACCINES: EFFECT ON LYMPHO- CYTE SUBPOPULATION STRUCTURE].

AIM: Study subpopulation structure of lymphocytes in healthy individuals under the effect of various influenza vaccines in an in vitro system. MATERIALS AND METHODS: Evaluation of immune- phenotype features of PBMCs, activated in vitro by immune-adjuvanted and unadjuvanted vaccines against influenza in healthy individuals, was carried out by using flow cytometry method. RESULTS: Grippol plus vaccine caused a more pronounced stimulating effect compared with subunit and split-vaccines on NK-cells, cells with markers of early activation CD45/CD25, induced the quantity of natural regulatory cells (CD4/CD25/Foxp3), increase of the number of B-cells and reduced the amount of cell types with apoptosis marker CD45/CD95. CONCLUSION: Immune-adjuvanted vaccine Grippol plus induced formation of effectors of both innate and adaptive immunity and possessed the most powerful potential regarding activation of various types of immune-competent cells compared with unadjuvanted vaccines.

[New ideas on the therapeutic effect of a combination of vaccines against pneumococcal, Haemophilus influenzae type b infection, and influenza in patients with chronic obstructive pulmonary disease].

AIM: To estimate the indicators of the therapeutic effect of combination vaccination against pneumococcal, Haemophilus influenzae type b infection, and influenza in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Clinical, bacteriological, and immunological studies, by determining the quality of life (QL), were conducted in COPD patients during a year after combination vaccination against pneumococcal, Haemophilus influenza type b infection, and influenza. RESULTS: One year after the vaccination, there were reductions in the number of COPD exacerbations by 3.7 times, in that of antibiotic therapy cycles by 3.4 times, in the levels of inflammatory mediators of interleukins 2 and 8 and interferon-γ, and in the synthesis of IgG antibodies to Streptococcus pneumoniae, Haemophilus influenzae type b, and influenza virus strains as compared to the baseline values. CONCLUSION: Combination vaccination against bacterial and viral infections substantially improves the major clinical parameters of COPD, positively affecting LQ indicators that generally characterize the therapeutic effect of immunization.

[Transplacental IgG against measles virus in umbilical blood of neonates from various regions of Russian Federation].

AIM: Determine content of protective transplacental IgG against measles virus in umbilical blood of neonates of various regions of Russian Federation. MATERIALS AND METHODS: Umbilical blood of 1147 neonates was studied, whose mothers had not previously had measles. 672 samples among those were from neonates of Moscow and Moscow Region, 475--from Rostov-on-Don. IgG values were determined in EIA using a standard kit from "Vector Best" (VectoKor-IgG). A kit from Euroimmun--Avidity: Anti-Measles Virus ELISA (IgG) was used for determination of avidity of IgG against measles virus. RESULTS: Protective (≥ 0.18 IU/ml) IgG against measles were registered in 79.9% of children in Moscow, Moscow Region and in 81.3% of neonates in Rostov-on-Don. Mean level of IgG in umbilical blood sera of neonates from the studied regions was within protective values (1.74 ± 0.13 IU/ml and 1.51 ± 0.09 IU/ml, respectively). Predominance of low level antibodies was noted in the studied samples (< 1.0 IU/ml), those are highly avid though (AI > 60%). In neonates from women aged 16 - 25 years in Moscow and Moscow Region protective antibodies were detected in 83.6%; 26 - 35 years--in 75%; women aged 36 - 43 years--in 88.2% of cases. Mean level of IgG in umbilical blood of neonates from mothers aged 36 - 43 years was 1.5 times higher than from mothers aged 16 - 25 years and 2 times higher than mothers 26 - 35 years of age. CONCLUSION: Neonates from Moscow, Moscow Region and Rostov-on-Don, similarly, in 79.9% and 81.3% of cases are protected from measles, respectively. Women aged 26-35 years in 25% of cases are a risk group for measles morbidity and require a closer attention during selection of vaccination tactics before conception, and their neonates--on reaching decree terms.

[Anti-hepatitis B vaccination and postvaccinal immunity stimulation in patients with chronic obstructive pulmonary disease].

The problem of the anti-hepatitis B vaccination of patients with chronic obstructive lung disease (COPD) was discussed due to the lack of studies concerning the developing of the postvaccinal immunity, especially when vaccination is combined with the immunomodulating treatment. The data on the vaccination safety and its influence on the clinical course of COPD are also insufficient. Therefore, in this work we investigated the efficiency of the antihepatitis B vaccination in adults with chronic obstructive pulmonary disease under the treatment with the immunomodulating Affonoleikin drug. A total of 93 patients were tested including 59 patients with severe and moderate COPD (aged from 35 to 65 years). 34 of these 59 patients were vaccinated against hepatitis B (Kombioteh) according to 0-1-6 month scheme, and 25 of them were vaccinated against hepatitis B during the treatment with Affinoleikin. The control group, consisted of 34 healthy patients. Our study demonstrated good tolerance and high immune efficiency of the anti-hepatitis B vaccine. However, after the first vaccination the level of HBs-AT was below protective level in patients with COPD compared to healthy patients. Also, 64 to 70 % of patients with COPD were seronegative excluding the patients receiving the Affinoleikin treatment, whose antibody titer was protective after the first vaccine dose, but did not reach the level typical of healthy patients. After the second vaccination we detected low and medium protective antibody levels in 58.9% of patients from the 1st group, whereas 41% were seronegative. Introduction of the third vaccine-dose led to fast and significant increase in the antibody level mainly in high concentrations with 100% seroconversion in all patients. Combined antihepatitis B vaccination and Affinoleikin treatment in patients with COPD leads to faster biosynthesis of HBs- AT in protective concentrations and decrease of seronegative response, but it has no effect on frequency and type of general and local postvaccinal response.

[Grippol, Vaxigrip and influvac vaccines--inductors of innate and adaptive immunity factor genes in human blood cells].

AIM: Study the effect of inactivated influenza vaccines on the activity of innate and adaptive immunity genes (TLR3, TLR4 and B2M), RNA-interference Dicer1-gene, production of cytokines (antiviral IFN type I and II, regulatory IL10, IL17) and pro-inflammatory factors IL1-ß, TNFα. MATERIALS AND METHODS: Gene expression was determined by rRT-PCR with authors' primers in human blood cells treated with various doses of the vaccines. Concentration of cytokines by enzyme immunoassay was measured in cultural fluid using "Vector-best" kits. RESULTS: The studied vaccines have characteristic effects on genetic level. Grippol vaccine predominately stimulates TLR4 gene, activates TLR3, B2M and Dicer1 genes. Influvac vaccine mostly induces TLR3 gene and to a lesser extent TLR4 gene, does not influence the expression of B2M gene and inhibits Dicer1 gene. Vaxigrip split vaccine--the most potent stimulator of gene activity at low doses. Its main targets are TLR3 and B2M genes. All the inactivated vaccines--inductors of high level of IFNγ, low level of TNFα and do not induce IL17. Grippol additionally stimulates secretion of IL1-ß, and Vaxigrip - IFNα. Subunit vaccines Grippol and Influvac that contain purified influenza virus hemagglutinins induce IL10 synthesis in blood cells. CONCLUSION: Immunogenetic characteristics of the inactivated influenza vaccines administered nowadays are obtained.

[Mechanisms of formation of post-vaccinal immune response in children immunized with APDT and ADT-M preparations].

AIM: Study the mechanisms of formation of cell and humoral immunity against pertussis, diphtheria and tetanus in children immunized with immunobiological preparations (APDT vaccine and ADT anatoxin). MATERIALS AND METHODS: 30 practically healthy children (6 - 9 years of age) immunized with APDT and ADT-M preparations had TLR2, TLR4 expression determined in mononuclear cells (MNC). Vaccine preparations (APDT, ADT-M, AD-M, AT) and Corynebacterium diphtheriae gravis tox+, C. diphtheriae mitis tox- and Bordetella pertussis 345 were used as ligands. Cytokine production was determined in EIA. Content of anti-diphtheria, anti-tetanus and anti-pertussis antibodies--by PHA reaction and EIA. RESULTS: During stimulation with vaccines and B. pertussis 345 strain MNC were characterized by an increase (p < 0.05) of expression level of TLR2 and TLR4 and did not respond to stimulation with C. diphtheriae gravis tox+ and C. diphtheriae mitis tox- strains. Similar results were obtained during study of cytokine production (TNFalpha, IL-1, IL-6). A direct correlation between levels of antitoxic antibodies against diphtheria and tetanus (R = 0.486), antibacterial antibodies against pertussis and diphtheria was detected (R = 0.529). CONCLUSION: Analysis of cytokine production profile and determination of surface TLR expression can be used during evaluation of functional status of innate immunity cells and intensity of post-vaccinal immunity.

[Species and quantitative characteristics of pharyngeal mucosa microflora in pregnant women].

AIM: Species and quantitative characteristics of upper respiratory tract (URT) mucosa microflora in women at gestation period. MATERIALS AND METHODS: The results of a bacteriological study of 68 samples of mucus from posterior pharyngeal wall in women at gestation period (from 14 weeks), 52 of those--from pregnant women with acute respiratory infection (ARI) symptoms and 16--from women without signs of disease, are presented. Qualitative and quantitative composition of microflora was studied by a generally accepted bacteriological method. RESULTS: During primary bacteriological study 111 microorganism cultures were isolated. 88 (79.3%) of strains belonged to Gram-positive flora, 20 (18.0%)--to Gram-negative, and Candida genus fungi constituted 3 (2.7%) isolates. Streptococcus pyogenes and Moraxella catarrhalis were isolated from pregnant women with ARI signs at 23.1% and 5.8% frequency of occurrence, respectively. A higher detectability of Staphylococcus aureus--in 31.3% and Candida spp.--in 6.3% of women who did not complain as opposed to patients with URT lesions (in 21.2 and 3.9%, respectively) was determined. In patients without ARI signs the amount of bacteria did not exceed 10(5)--10(6) CFU/ml, in pregnant women with ARI diagnosis in 8 of 52 cases semination of pharyngeal mucuswas observed--10(7)--10(8) CFU/ml. CONCLUSION: Prevalence of S. aureus, Streptococcus agalactiae, S. pyogenes, Streptococcus mutans in composition of pharyngeal mucus microflora of pregnant women both with URT lesion signs and without them was shown, however the degree of semination by pathogens in the groups was different that determined the severity of disease manifestations.