[The clinical aspects of efficiency of the prevention of pneumococcal infection with vaccines in chronic obstructive pulmonary disease patients living in the West Siberian Region].

AIM: To evaluate the impact of vaccination against pneumococcal infection on the clinical aspects of the underlying disease in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: The study conducted in the West Siberian Region (Omsk and Tyumen) enrolled 200 COPD patients aged 30 to 55 years, of whom 50 people in each city were vaccinated with Pneumo 23, as well as 50 unvaccinated persons in each city formed a comparison group. Physical examination, questionnaire survey, and medical history data collection were made during a year before vaccination and after it. Changes in the number of COPD exacerbations, hospital admissions, and disability days were compared in the groups of Pneumo 23-vaccinated and unvaccinated patients. RESULTS: In Pneumo 23-vaccinated patients with COPD, the number of its exacerbations, hospital admissions, and disability days within a year of starting the study were fewer than in the unvaccinated patients, with the more effect being seen in the Omsk dwellers, which had a beneficial effect on the clinical state of the vaccinated. CONCLUSION: Incorporation of pneumococcal vaccine along with antirecurrent, standard therapy may serve as one of the tools to alleviate COPD.

[IgE-response after administration of pandemic vaccine strain A/California/7/2009 (H1N1)v].

Changes in total and allergy-specific IgE (IgE-antibodies) in 70 healthy volunteers vaccinated with influenza vaccine subunit strain A/California/7/2009/(H1N1)v. Safety of this vaccine was shown. Repeated second dose administration is not accompanied by increase in IgE-antibodies to egg components. Vaccine injection results in decrease of total IgE in patients with elevated IgE at baseline.

[Dynamics of cytokine production in adults after administration of influenza vaccine from A/California/7/2009 (H1N1) strain].

AIM: Study dynamics of IFNalpha, IFNgamma, TNFalpha cytokines in healthy adults after administration of inactivated subunit monovalent influenza vaccine, A/California/7/2009 (H1N1) strain. MATERIALS AND METHODS: Levels of IFNalpha, IFNgamma, TNFalpha cytokines were studied in blood sera of 58 mostly healthy adults aged 18 - 60 years. Kits for enzyme immunoassay determination of cytokine levels (Vector-Best, Novosibirsk) were used in the study. Antibody titers to A/California/7/2009 (H1N1) strain were determined at analogous time by using microneutralization reaction (MNR). RESULTS: Changes in the level of IFNalpha, IFNgamma, TNFalpha in healthy volunteers immunized by pandemic influenza vaccine were evaluated. Vaccine was safe. Two immunizations did not result in an increase of TNFalpha level that is an additional evidence of vaccine safety. IFNalpha level had a tendency to increase in vaccinated volunteers. IFNgamma levels in volunteers with normal level of this cytokine (below 10 pg/ml) were increased significantly after the second immunization (from 2.66 +/- 2.48 to 5.21 +/- 2.56). Correlation analysis showed that there is a strong negative association between IFNalpha, IFNgamma and seroconversion.

[Immunogenicity of inactivated subunit adsorbed monovalent vaccine against influenza A/California/7/2009 (H1N1) strain].

The immunogenicity of Pandeflu subunit vaccine against influenza A/California/7/2009 (H1N1) was evaluated in 70 healthy volunteers aged 18 to 60 years. The vaccine was intramuscularly injected twice at an interval of 28 days. Each dose (0.5 ml) contains A(HIN1) influenza virus hemagglutinin (15 +/- 2.2 microg), aluminum hydroxide (Denmark) (0.475 +/- 0.075 microg), and the preservative thiomerosal (merthiolate) (50 +/- 7.5 microg). The level of antibodies was determined in the microneutralization assay. After administration of two doses of the vaccine at a 28-day interval, the geometric mean antibody titer (GMAT) reached 1:21.1 with a further increase to 1:30 (the baseline GMAT) was 1:6.1). The frequencies of seroconversion and seroprotection were 71.4 and 59.2%, respectively; the antibody increase factor was 4.92, which meets the CPMP criteria. The administration of the vaccine did not result in adverse reactions in the postvaccination period.

[Clinical trial of new inactivated influenza vaccine "Grifor"].

AIM: To confirm and prove on the extended contingent of volunteers the non-reactogenicity, safety and immunogenicity of "Grifor" vaccine in comparative trial with registered in Russia commercial vaccine "Vaxigrip". MATERIALS AND METHODS: Phase II clinical trial was performed on the research bases of Mechnikov Institute of Vaccines and Sera and Institute of Influenza. In single-blind comparative prospective randomized trial 300 adult volunteers (150 volunteers on each base) aged 18 - 60 y.o. were divided on 3 equivalent groups. Assessment of antigenic characteristics of "Grifor" vaccine was performed using hemagglutination inhibition assay (HAI) with chicken erythrocytes measuring geometric mean titer (GMT), seroconversion factor as well as level of seroconversion and seroprotection. RESULTS: Previously performed studies proved non-reactogenicity, safety and high immunogenicity of "Grifor", whereas this comparative trial performed with commercial vaccine "Vaxigrip" did not reveal significant advantage in any of studied vaccine. CONCLUSION: "Grifor" vaccine meet the requirements of both EMEA CPMP and methodic guidelines MY 3.3.2. 1758-03 for inactivated influenza vaccines, which allows to register vaccine "Grifor" in Russian Federation.

[Study of reactogenicity, safety and immunogenicity of inactivated virosomal split influenza vaccine "Grifor" during phase I clinical trial].

Phase I clinical trial of inactivated virosomal split influenza vaccine "Grifor" was conducted in the Mechnikov Research Institute of Vaccines and Sera as accredited base for such trials. Forty healthy volunteers (males and females) aged 18 - 50 years consented to participate in the trial. Reactogenicity, safety, and immunogenicity of new Russian influenza vaccine were assessed. Analysis of obtained results showed that there was evidence of safety and low reactogenicity of the vaccine as well as of its high immunogenic characteristics, which satisfied both the EMEA's Committee for Proprietal Medicinal Products criteria and requirements of Federal Service for Surveillance for Protection of Consumers Rights and Human Welfare (MU 3.3.2.1758-03) for inactivated influenza vaccines.

[Cytokine profile and level of antibodies after administration of split-vaccine against influenza to adults].

Serum concentrations of cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-8) and antibody levels to influenza virus antigens were studied in adults vaccinated with split-vaccine against influenza. Analysis of antibody titers 21 days after vaccination compared with baseline levels revealed high immunogenicity of vaccine in terms of mean geometric titers increase as well as sufficient levels of seroprotection and seroconversion. Study of cytokine profile showed absence of significant changes of IFN-gamma, TNF-alpha, IL-2, IL-4 levels and considerable variability of IL-6 and IL-8 baseline levels as well as their dynamics after vaccination. Direct correlation between IL-6 and IL-8 levels was observed during whole period post-immunization. Inverse correlation between IFN-gamma and fold increase of antibody level was established which can be used as prognostic criterion of influenza prevention effectiveness.

[Comparative clinical trial of vaccines against avian influenza].

Scientic-production association "Microgen" has finished 1st phase of clinical trials of candidate vaccines against avian influenza in order to assess their reactogenicity, safety, and immunogenicity. Two vaccines constructed from NIBRG-14 vaccine strain [A/Vietnam/1 194/2004 (H5N1)], obtained from World Health Organization, were studied: "OrniFlu" (inactivated subunit influenza vaccine adsorbed on aluminium hydroxide) and inactivated polymer-subunit influenza vaccine with polyoxydonium (IPSIV). Clinical trial of the vaccines with different quantity of antigen (15, 30, and 45 mcg of H5N1 virus hemagglutinin) was carried out in Influenza Research Institute (St. Petersburg) and in Mechnikov Research Institute of Vaccines and Sera (Moscow). Analysis of results allowed to conclude that both vaccines were safe, well tolerated and characterized by low reactogenicity. Two-doses vaccination schedule was needed to meet required seroconversion and seroprotection rates (> or =1:40 in > or =70% of vaccinated volunteers). "Orni-Flu" vaccine containing 15 mcg of hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) in one dose as well as IPSIV containing 45 mcg of hemagglutinin and 0.75 mg of polyoxydonium in one dose were most immunogenic after 2 doses - seroprotection rates in microneutralization assay were 72.2% and 77.0% respectively. Marked influence of aluminium hydroxide content on immunogenicity of the "OrniFlu" vaccine was confirmed in the study. Optimal quantity of adjuvant was 0.5 mg per dose. According to basic concept of vaccine development, preference is given to vaccine that under minimal quantity of antigen induces sufficient specific immune response and is safe in volunteers. "OrniFlu" vaccine containing 15 mcg of H5N1 virus hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) corresponded to these requirements that allowed researchers to recommend it for clinical trials of 2nd phase.

[House-dust mites allergen for specific immunotherapy by oral administration: experimental study].

The oral medicinal form of house-dust allergen has been prepared with the use of new technology. To produce the preparation, the standard water-saline extract obtained from house-dust mites (Dermatophagoides farinae) allergen has been used. This preparation is chemically stable and does not lose its biological activity for 2 - 3 years of storage. The microbiological purity of the allergen meets the requirements for oral preparations. The allergen has proved to be safe in cases of prolonged administration and has no chronic toxicity. As shown with the use of immunochemical methods, the preparation has high immunogenicity and lower allergenicity. This preparation may be recommended for clinical trials on a limited circle of subjects.

[Study of allergens from vegetables, fruits and berries]. / Izuchenie allergenov iz ovoshchei, fruktov i iagod.

Different methods of obtaining allergens from vegetables, fruit and berries have been evaluated. Two technologies for obtaining food allergens have been considered; of these, Coca's method has proved to be more technological, economical and less labor-consuming. The newly developed technology has made it possible to obtain stable, safe and specifically active allergens which may be used for diagnosing food allergy.

[An allergen from Blattella germanica cockroaches and its immunological properties]. / Allergen iz tarakanov Blattella germanica i ego immunologicheskie svoistva.

The optimum method for obtaining allergenic preparation with high specific activity and stable physico-chemical characteristics from cockroaches of the species B. germanica was developed. The quantitative content of cockroach allergens Bla g1 and Bla g2 was determined in experimental batches. The age structure of sensitization to cockroaches in 124 bronchial asthma patients (50 adults and 74 children) was studied. Specific IgE antibodies to B. germanica were detected in 34% of the examined adults and 63.5% of the children.

[Increased sensitivity to cockroaches of the species Blattella germanica in patients with allergic diseases]. / Izuchenie povyshennoi chuvstvitel'nosti k tarakanam Blattella germanica u bol'nykh s allergicheskimi zabolevaniiami.

Sensitization to Blattella germanica (B.g.) was studied in 290 allergic patients having increased sensitivity to house dust (HD). The study carried out by ELISA techniques with the use of allergen especially developed by the authors, revealed that the sera of adults and children with bronchial asthma (BA) contained high levels of IgE antibodies (Ab) to B.g. in 34 and 63.5% of cases, respectively. The presence of pronounced IgE-linked sensitization of target cells of BA patients was confirmed in leukocyte alteration test and in the natural leukocyte migration inhibition test. Increased sensitization to B.g. was shown to be the second in the total spectrum of sensitization to different arthropod species in house dust, and the presence of mixed sensitization to B.g. and HD mites was not due to cross reactions caused by main mite allergens. The content of IgG and IgG4 Ab to B.g. in BA patients exceeds that in healthy subjects, the tendency towards reverse correlation (r = -0.4) between the content of specific IgE and IgG Ab being revealed in the former. An essential role of sensitization to cockroaches in pathogenesis of BA is emphasized.

[Storage mites as the source of household allergens]. / Ambarnye kleshchi kak istochnik bytovykh allergenov.

Storage mites of the families Acaridae and Glycyphagidae attracted attention as the source of household allergens. Storage mites occurring in house dust were studied. The fauna of storage mites in house dust was represented by two families. The dominating species, both in the relative amount and occurrence, were Tyrophagus putrescentiae and Chortoglyphus arcuatus. In addition, Caloglyphus rodionovi and Carpoglyphus lactis occur regularly. The specific activity of allergenic extracts obtained from storage mites was studied in ELISA. They were shown to have sensitizing and immunogenic properties. The study revealed that storage mites possessed specific determinants and those common with pyroglyphid, not linked with allergens of groups 1 and 2.