Clinical and Immunological Efficiency of Bacterial Vaccines at Adult Patients With Bronchopulmonary Pathology

Study Overview
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Brief Summary
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Goal: to to examine the formation of postvaccination immunity and evaluate the therapeutic effect of bacterial vaccines in patients with inflammation diseases of bronchopulmonary system. Objectives of the study: assessment of microbiocenosis mucous membranes of the upper respiratory tract in patients with bronchopulmonary pathology before and after use of bacterial vaccines. Identification of mayor lymphocytes subpopulations in patients in the dynamics of the vaccination process. Study the profile of humoral immune response in patients under different schemes of vaccination. Assessment of the clinic and functional status bronchopulmonary system in the immunized patients.

Detailed Description
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Methods: Immunoglobulin G (IgG)-antibodies against Streptococcus pneumoniae (S. pneumoniae) - solid-phase enzyme-linked immunoelectrodiffusion essay (ELISA). General levels of Immunoglobulin A (IgA), Immunoglobulin M (IgM), IgG, Immunoglobulin E (IgE) in sera - radial immunodiffusion. Phagocytic activity (granulocytes, monocytes), nitroblue tetrazolium test; T-lymphocytes, T-helpers (cluster of differentiation, CD3+CD4+), cytotoxic T-lymphocytes (СD3+CD8+), B-lymphocytes (CD19+); NK-cells (CD3-CD16+CD56+), NKT-cells (CD3+CD16+CD56+), activated T-cells (human leucocyte antigens, CD3+HLA DR+), CD3-HLA DR+. Microbiological examination of sputum. Determining the clinical effectiveness of vaccination. the number of exacerbations of chronic bronchopulmonary pathology for the year prior to vaccination and during the first and fourth years after vaccination; the number of courses of antibiotic therapy a year prior to vaccination and during the first and fourth years after immunization; the number of hospitalizations for acute exacerbations of chronic bronchopulmonary disease during the year prior to vaccination and during the first and fourth years after immunization. Method of estimating quality of life associated with health in patients with chronic bronchopulmonary pathology (asthma control questionnaire (ACQ-5), COPD assessment test (CAT)). Characteristics of variables (arms 1-8). The age of patients (years): mean (standard deviation) [min; median; max] for normally distributed variables; median [Q25; Q75] - for variables with distribution different from normal. Gender: male/female. Indicators of immune status IgG antibodies to S. pneumoniae IgA, g/l [0,4-3,5] IgM, g/l [0,7-2,8] IgG, g/l [8-18] IgE, IU/ml [< 100] Phagocytic index (granulocyte), % [82-90] Phagocytic index (monocytes), % [75-85] The participation rate of spontaneous NBT-test (neutrophils), % with intensity of 0.2.e. [7-14] The index of activity induced NBT-test (neutrophils), % if intensity >of 0.36.e. [>28] The percentage of NBT-positive cells in spontaneous test, % [2-19] Circulating immune complexes (CEC) cond. units [0,055-0,11] CD3+, % [55-80] CD3+CD4+, % [31-49] CD3+CD8+, % [12-30] CD19+, % [5-19] CD3-CD16+CD56+, % [6-20] CD3+CD16+CD56+, % [<10] CD3-HLA DR+, % [5-20] CD3+HLA DR+, % [<12] CD45RO. The reference value = 0,2. Microbiological examination of sputum: frequency of selection of certain microorganisms are presented as absolute number of cases and % in the respective groups. Evaluation of early post-vaccination period The General condition (satisfactory/unsatisfactory) Local reactions: pain (n/%), redness (n/%, cm), consolidation (n/%, cm) General reactions: Temperature 37,0-37,5 (n/%) Temperature of 37.6-38,5 (n/%) A temperature of 38.6 and > (n/%) Headache (n/%) Malaise, fatigue (n/%) Joint pain (n/%) Muscle pain (n/%) Health related quality of life (HRQoL): CAT-test (for Chronic obstructive pulmonary disease (COPD) patients), ACQ-5 (for asthma patients).

Official Title
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Pathogenetic Justification and Clinical and Immunological Efficiency of Application Bacterial Vaccines at Adult Patients With Bronchopulmonary Pathology

Conditions
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Chronic Obstructive Pulmonary Disease, Asthma, Pneumococcal Infections

Intervention / Treatment
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* Biological: Prevenar-13
* Biological: Pneumo-23


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals of both sexes from 18 years with a diagnosis of COPD or Bronchial Asthma; The presence of signed and dated informed consent to participate in a clinical study; The ability to perform the requirements of the Protocol; For women of childbearing age is a negative result of a pregnancy test before vaccination. Diagnostic criteria for: - COPD: dyspnea: progressive (worsens over time), increases with exertion, persistent; chronic cough (may appear sporadically and may be unproductive); chronic expectoration; the impact of risk factors in the medical history (Smoking, occupational dust pollutants and chemicals); widespread wheeze on auscultation of the chest and/or distant wheezing in the chest; family history of COPD; spirometric data confirming the presence of fixed bronchial obstruction. Exclusion Criteria: Vaccination against pneumococcal infection in anamnesis; Application of preparations of immune globulin or blood transfusion within last three months prior to clinical studies; Prolonged use (more than 14 days) immunosuppressants or other immunosuppressive drugs within 6 months prior to the start of the study; Any confirmed or suspected immunosuppressive or immunodeficient condition, including Human Immunodeficiency Virus (HIV) infection; A history or currently hematologic and other cancers; A positive reaction for HIV infection, viral hepatitis B and hepatitis C; The presence of respiratory, cardio-vascular insufficiency, impaired liver and kidney function, established during a physical examination at visit number 1; Pronounced congenital defects or serious chronic diseases in the acute stage, including any clinically important exacerbation of chronic diseases of the liver, kidney, cardiovascular, nervous system, mental diseases or metabolic disorders, confirmed by the history or objective examination (pulmonary: cystic fibrosis, lung abscess, empyema, active tuberculosis; extra-pulmonary: congestive heart failure, malabsorption, chronic renal and hepatic failure, cirrhosis, malignancy, immunodeficiency, cirrhosis of the liver); Severe allergic reactions in anamnesis, autoimmune disease; The presence of acute infectious and/or communicable illnesses within 1 month prior to study; History of chronic alcohol abuse and/or drug use; Exacerbation of chronic diseases; Breastfeeding; Pregnancy; Participation in any other clinical study within the last 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COPD with Prevenar-13 (1)<br>33 patients with COPD. Standard therapy with Prevenar-13. | Biological: Prevenar-13<br>* Conjugate 13 serotype pneumococcal vaccine<br>* Other names: PCV13;|
| Experimental: Asthma with Prevenar 13 (2)<br>34 patients with asthma. Standard therapy with Prevenar 13. | Biological: Prevenar-13<br>* Conjugate 13 serotype pneumococcal vaccine<br>* Other names: PCV13;|
| Experimental: COPD with Pneumo-23 (3)<br>25 patients with COPD. Standard therapy with Pneumo-23. | Biological: Pneumo-23<br>* Polysaccharide 23-valent pneumococcal vaccine.<br>* Other names: PPV23;|
| Experimental: Asthma with Pneumo-23 (4)<br>25 patients with asthma. Standard therapy with Pneumo-23. | Biological: Pneumo-23<br>* Polysaccharide 23-valent pneumococcal vaccine.<br>* Other names: PPV23;|
| Experimental: COPD with Pneumo-23/Prevenar-13 (5)<br>32 patients with COPD. Standard therapy, vaccinated with pneumococcal polysaccharide vaccine/pneumococcal conjugate vaccine (PPV23/PCV13). | Biological: Prevenar-13<br>* Conjugate 13 serotype pneumococcal vaccine<br>* Other names: PCV13;Biological: Pneumo-23<br>* Polysaccharide 23-valent pneumococcal vaccine.<br>* Other names: PPV23;|
| Experimental: Asthma with Pneumo-23/Prevenar-13 (6)<br>18 patients with Asthma. Standard therapy, vaccinated with PPV23/PCV13. | Biological: Prevenar-13<br>* Conjugate 13 serotype pneumococcal vaccine<br>* Other names: PCV13;Biological: Pneumo-23<br>* Polysaccharide 23-valent pneumococcal vaccine.<br>* Other names: PPV23;|
| Experimental: COPD with Prevenar-13/Pneumo-23 (7)<br>25 patients with COPD. Standard therapy, vaccinated with PCV13/PPV23. | Biological: Prevenar-13<br>* Conjugate 13 serotype pneumococcal vaccine<br>* Other names: PCV13;Biological: Pneumo-23<br>* Polysaccharide 23-valent pneumococcal vaccine.<br>* Other names: PPV23;|
| Experimental: Asthma with Prevenar-13/Pneumo-23 (8)<br>27 patients with Asthma. Standard therapy, vaccinated with PCV13/PPV23. | Biological: Prevenar-13<br>* Conjugate 13 serotype pneumococcal vaccine<br>* Other names: PCV13;Biological: Pneumo-23<br>* Polysaccharide 23-valent pneumococcal vaccine.<br>* Other names: PPV23;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Without Exacerbations of the Underlying Disease, Antibiotic Use and Hospitalisation. | Number of patients without exacerbations of the underlying disease, antibiotic use and hospitalisation. | Baseline (1 year prior to vaccination), 1 year after vaccination, 4 years after vaccination | 
| The Number of Exacerbations of the Underlying Disease, Antibiotic Use and Hospitalisation | The number of exacerbations of the underlying disease, antibiotic use and hospitalisation. The average number of exacerbations per 1 patient = total exacerbations in the group / number of patients in the group. This is not a mean value. | Baseline (1 year prior to vaccination), 1 year after vaccination, 4 years after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seeding Frequency S. Pneumoniae From Sputum in Patients With COPD | Seeding frequency S. pneumoniae from sputum in patients with COPD | Baseline, after 1 and 4 years after vaccination | 
| Average CAT (COPD) and ACQ-5 (Asthma) Score | CAT - COPD Assessment Test, min. = 0, max. = 40, higher scores mean a worse outcome. ACQ-5 - Asthma control questionnaire, min. = 0, max. = 6, higher scores mean a worse outcome. | Baseline, after 1 and 4 years after vaccination | 
| Phagocytic Activity in Patients With COPD at Baseline, 1, 2, and 6 Weeks After PCV13 and PPV13 Vaccination | Phagocytic index (granulocytes), phagocytic index (monocytes), activity of a spontaneous HCT test (neutrophils), activity of an induced HCT test (neutrophils), percentage of HCT-positive white blood cells in a spontaneous test. The phagocytic index was calculated according to the following formula: phagocytic index = (total number of engulfed cells/total number of counted macrophages) × (number of macrophages containing engulfed cells/total number of counted macrophages) × 100 (phagocytic index) The phagocytic index was calculated by counting at least 100 bacteria phagocytized by certain number of phagocytic cells/macrophages and expressed following formula (Mamnur Rashid 1997): Phagocytic index = Total no. of phagocytized bacteria /No of phagocytic cells phagocytizing bacteria. Activation index = % formazan positive cells (FPC) in NBT stimulated / % formazan positive cells (FPC) in NBT Spontaneous. | Baseline, 1, 2, 6 weeks after PCV13 and PPV13 vaccination | 
| Immunophenotype of Blood Lymphocytes in Patients With COPD | Immunophenotype of blood lymphocytes in patients with COPD at baseline, 1, 2 and 6 weeks after PCV13 and PPV23 vaccination. It was pre-specified to report data from only the COPD - Prevenar-13 and the COPD - Pneumo-23 Arms/Groups for this Outcome Measure. This is due to the fact that we tried to study the effect of PCV13 and PPV23 on immunity values. The study of the immunological effects of vaccination in the early post-vaccination period was carried out in 2 groups of patients: 20 patients with COPD vaccinated with PCV13; 20 patients with COPD vaccinated with PPV23. These patients were selected from patients of the main groups (COPD - Prevenar-13 (1), COPD - Pneumo-23 (3)). | Baseline, 1, 2, 6 weeks after PCV13 and PPV13 vaccination | 
| IgA, IgM, IgG, IgE, Circulating Immune Complexes (CIC) | IgA, IgM, IgG, IgE, circulating immune complexes (CIC) in serum at baseline, 1, 2 and 6 weeks after vaccination. It was pre-specified to report data from only the COPD - Prevenar-13 and the COPD - Pneumo-23 Arms/Groups for this Outcome Measure. This is due to the fact that we tried to study the effect of PCV13 and PPV23 on immunity values. The study of the immunological effects of vaccination in the early post-vaccination period was carried out in 2 groups of patients: 20 patients with COPD vaccinated with PCV13; 20 patients with COPD vaccinated with PPV23. These patients were selected from patients of the main groups (COPD - Prevenar-13 (1), COPD - Pneumo-23 (3)). | Baseline, 1, 2, 6 weeks after PCV13 and PPV13 vaccination in COPD | 
| CD45RO | CD45RO expression on lymphocytes in serum at baseline, 1 and 4 years after vaccination. These patients were selected from patients of the main groups. | Baseline, 1 and 4 years after vaccination | 
| Specific IgG Levels in Vaccinated Patients With COPD to S. Pneumoniae Serotypes | Mean specific IgG levels in vaccinated patients with COPD to S. pneumoniae serotypes at baseline, 6 and 12 months after vaccination | Baseline, 1 and 12 months after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumococcal vaccines