Immunoprophylaxis of acute respiratory diseases with bacterial multicomponent vaccine VP-4 in children at preschool institutions

The prophylactic action of polycomponent vaccine B[symbol: see text]-4, prepared from the antigens of opportunistic bacteria, on morbidity rate in acute respiratory diseases (ARD) of bacterial and mixed (bacterial and viral) etiology in 121 children aged 2-5 years, attending pre-school institutions was evaluated. For comparison, a group of 118 children of the same age from the same institutions was formed. The vaccine was introduced after the schedule consisting of 3 intranasal and 6-9 oral administrations made at intervals of 3-4 days. The duration of the course of immunization was 26 +/- 4 days. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity was evaluated by the number of ARD cases and their duration per child. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity lasted 14 months (the term of observation) after immunization and was manifested by a decrease in the number and duration of ARD cases after administration of the preparation, also in a group of highly susceptible children.     

The reactogenicity and safety of a multicomponent vaccine (VP-4) in the prevention of acute respiratory diseases in preschoolers

The reactogenicity and safety of poly-component vaccine (VP-4), prepared from the antigens of opportunistic bacteria, in the prophylaxis of acute respiratory diseases (ARD) in children aged 2.6-6 years. The vaccine was administered intranasally in 3 administrations and orally in 6-8 administrations at intervals of 3-4 days for a period of 24 +/- 4 days. The prophylaxis of ARD with the use of VP-4 was carried out in 168 children in 4 children's preschool institutions. The control group was made up of 120 children, attending the same institutions. The study revealed that VP-4 had low reactogenicity and induced short-time systemic and local reactions (common cold, cough). The administration of VP-4 at a period of the epidemic rise on influenza and ARD morbidity did not lead to an increase in the frequency and duration of ARD in the vaccinees, as well as to the exacerbation of chronic infection and the allergization of the body.     

Naso-subcutaneous application of the polycomponent vaccine VP-4 for the treatment of patients with bronchial asthma and chronic obstructive bronchitis

Bacterial polycomponent vaccine (VP-4) earlier developed at the Mechnikov Research Institute for Vaccines and Sera on the basis of antigenic complexes of Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Staphylococcus aureus was used within the program of clinical trials, for the treatment of 30 patients aged 16-59 years with the atopic and mixed form of bronchial asthma and chronic obstructive bronchitis by the combined naso-subcutaneous application. A good therapeutic effect produced by the vaccine was registered in 83.3% of the patients. It was manifested by a lower frequency of acute respiratory diseases and bronchopulmonary diseases as well as decreased need in antibiotic therapy. In the group of comparison a good effect was noted in 40% of the patients during 6 months of observation (statistically significant difference). Side effects caused by the administration of the vaccine were transitory, had mainly local character and disappeared without any treatment. In 1 patient the development of anaphylactic shock was observed. The positive effect of vaccine VP-4 could be attributed to the improved indices of cell-mediated immunity, an increased synthesis of alpha- and gamma-interferon, a droped level of IgE and specific IgG antibodies to Staphylococcus sp., Klebsiella sp., Proteus sp., Escherichia coli.     

Multicomponent vaccine VP-4 in the therapy of allergic diseases

In the present study the results of the polycomponent vaccine B[symbol: see text]-4 use for the therapy of patients with bronchial asthma (BA) and latex allergy were generalized. The vaccine was introduced by the nasal-subcutaneous or nasal-oral administration simultaneously with the basic therapy. Te studies were conducted first on limited groups of patients, then in the course of the State Trial with the use of placebo control. Excellent and good effect lasting for 1 year and over was registered in 36 patients (66.7%) out of 54 BA patients receiving the vaccine by the intranasal-subcutaneous method. Immunotherapy produced no positive effect in 13 patients (24.1%). Out of 35 examined patients receiving the vaccine by the intranasal oral method, excellent and good effect was registered in 26 patients (74.2%). No effect was registered in 4 patients (11.4%). In the group of 28 patients receiving placebo simultaneously with the basic therapy positive dynamics in the course of the disease was observed only in 3 patients. Treatment with polycomponent vaccine B[symbol: see text]-4 led to a prolonged (to a year and more) decrease in the frequency and severity of exacerbations, contributed to the prolongation of remissions and to a decrease in the amount of administered medicinal preparations, especially systemic corticosteroids. Immunotherapy ensured the correction of the content of lymphocyte subpopulations with markers CD3, CD4, CD72 and a rise in the titers of antibodies to antigens contained in the preparation. The use of therapeutic polycomponent vaccine B[symbol: see text]-4 for the treatment of patients with latex allergy ensured the state of prolonged remission in this group of patients. On the basis of our investigations we believe that the use of the therapeutic polycomponent vaccine B[symbol: see text]-4 may be included into the basis therapy of allergic diseases.     

Dynamics of autoantibodies in elderly persons in the process of vaccination with Grippol and multicomponent vaccine VP-4

The dynamics of antibodies to organ specific and organ nonspecific antigens in the process of combined immunization with Grippol, an influenza polymer subunit vaccine and polycomponent vaccine VP-4 used for prophylaxis of acute respiratory infections, was under study. Persons aged 65 years and older were vaccinated. Grippol alone was introduced in a single subcutaneous injection into 92 persons and Grippol in combination with vaccine VP-4--to 103 persons. B[symbol: see text]-4 Vaccine was introduced intranasally and orally (6-8 doses). The administration of vaccine VP-4 was started simultaneously with vaccination with Grippol. Prior to immunization and 1 and 5 months later autoantibodies to the following antigens were detected: DNA (native and denaturated), collagen, elastin, myelin basic protein, microsomal fractions of kidneys, lungs, heart, liver, intestine, pituitary body, thyroid gland, pancreas, adrenal glands, ovaries, mucous and muscular layers of stomach. The number of persons with the level of antibodies at least to one of the antigens under study exceeding the normal values prior to vaccination varied from 19.4 +/- 8.6% to 41.5 +/- 7.7%, the average values of positive sera being 0.26 +/- 0.05 to 0.32 +/- 0.08 delta OD. One and 5 months after vaccination both values varied within the same limits in both groups. Immunization with Grippol as well as with its combination with vaccine VP-4 was found to increased spectrum of antibodies to tissue antigens and their increased content. The data give evidence that Grippol and vaccine Vp-4, introduced according to the immunization schedule used in these experiments, do not induce development of autoimmune processes.     

TT virus loads and lymphocyte subpopulations in children with acute respiratory diseases

TT virus (TTV) produces chronic plasma viremia in around 90% of healthy individuals of all ages and has, therefore, been proposed as a commensal human virus. We recently demonstrated that in children hospitalized for acute respiratory diseases high TTV loads were associated with severe forms of disease. Here, we report that in such children TTV loads showed an inverse correlation with the percentage of circulating total T and helper T cells and a direct correlation with the percentage of B cells. Thus, florid TTV replication might contribute to lymphocyte imbalances and, possibly, immunosuppressive effects, thus resembling related animal viruses.     

The role of respiratory tract viruses in the etiology of obstructive bronchitis in infants

Out of 524 children with acute respiratory infections in 141 obstructive bronchitis was diagnosed (OZO). Seventy cases could be linked to viral infection. Viral infections tested (influenza virus A, B, parainfluenza typ 1-3, RSV, adenoviruses) were more frequently associated with OZO than other acute respiratory infections of unknown etiology. Majority infections induced by influenza virus A and parainfluenza virus typ 2 were accompanied by OZO symptoms. Of the highest risk of acquiring OZO despite of viral infection participation, were children of 4-12 months of age. OZO associated viral infections prevailed during autumn-winter season, while in spring-summer period undetermined factors were the major cause of OZO. In serum samples of children with OZO, despite of etiology of the disease, higher level of IgE was found than in a group of children without the symptoms. In the case of OZO of unestablished etiology the level of serum IgE was significantly higher than in the cases when viral etiology of the disease was found.     

Etiology of acute bronchitis in young children

In the microbiological examination of 132 children aged 0-3 years with acute bronchitis, Streptococcus pneumoniae and Haemophilus influenzae at a concentration of greater than or equal to 10(4) cells/ml, as well as different species of opportunistic bacteria, were isolated from tracheobronchial washings obtained from 100 of these children. S. pneumoniae and H. influenzae were found to play the leading role in the etiology of the acute bacterial inflammatory process in acute bronchitis in children.     

Interferonogenic properties of prodigiozan and its effectiveness in treating acute respiratory diseases in children

The capacity of prodigiozan to stimulate interferon production in the cell culture of the human palatine tonsil lymphocytes was studied. The interferonogenic properties of prodigiozan administered in the form of aerosols to children were also investigated. The efficacy of the prodigiozan aerosols in treatment of children with viral respiratory diseases was estimated. It was shown that prodigiozan stimulated interferon production in the cell culture of the tonsil lymphocytes (the titers of 1 : 2--1 : 8) and induced formation of endogenic interferon in the host (in the tonsils and blood serum) 24 hours after the aerosol administration. 100 micrograms of prodigiozan administered in the form of aerosols in a single dose or in 2 doses at an interval of 1--2 days had a pronounced therapeutic effect 1--2 days after the administration. The use of prodigiozan in treatment of children with acute viral respiratory infections promoted a decrease in the frequency of complications, such as pneumonia and otitis. The data are indicative of the validity of prodigiozan in treatment of children with acute respiratory infections.     

The role of Chlamydia pneumoniae in etiology of acute bronchitis in children

During examination of 60 children aged 3-15 years with manifestations of acute bronchitis Chlamydia pneumoniae antigen was detected in their nasal and pharynx smears in 11.7% of cases with the use of enzyme immunoassay and indirect immunofluorescence test. In 10% of cases chlamydial pneumonia was diagnosed serologically. In the course of complex laboratory diagnostics C. pneumoniae was detected in 13.3% of cases. The most complete information could be obtained by a combination of different methods of the antigen detection as well as specific IgG and IgM antibodies.     

TT virus in the nasal secretions of children with acute respiratory diseases: relations to viremia and disease severity

The natural history and pathogenic potential of the recently identified TT virus (TTV) are currently a matter of intensive investigation. In an attempt to shed some light on these issues, nasal and blood specimens of 1- to 24-month-old children hospitalized with a clinical diagnosis of acute respiratory disease (ARD) were examined for the presence, load, and genetic characteristics of TTV. The results have indicated that at least in young children, the respiratory tract not only represents a route by which abundant TTV can be shed into the environment but also may be a site of primary infection and continual replication. Although we found no compelling evidence that TTV was the direct cause of ARD in some of the children studied, the average loads of TTV were considerably higher in patients with bronchopneumonia (BP) than in those with milder ARD, raising interesting questions about the pathophysiological significance of TTV at this site. Furthermore, group 4 TTV was detected almost exclusively in children with BP.     

Protective effect of the aerosol immunization of mice with the polycomponent vaccine Immunovac VP-4 after the challenge of the animals with Klebsiella pneumoniae virulent strain

Used four schemes of the administration of the preparation with different time of the exposition of the animals in an aerosol chamber were tested with their subsequent intraperitoneal challenge with K. pneumoniae virulent strain K16. Irrespective of the number of immunization courses, the administration of the preparation made at intervals of 1 day, or daily, did not ensure any protective effect, but only led to an insignificant increase in their survival time in comparison with nonimmunized animals. After intervals between immunizations were increased to 3 days the protective effect of aerosol immumization was obtained (the survival rate was 65-80 % and considerably differed from that of the controls). The protective effect of aerosol immunization thus obtained was comparable with the effectiveness immunization made in a single subcutaneous injection. Aerosol immunization resulted in low antibody titers to the antigens contained in the vaccine, while after a single subcutaneous injection high antibody titers to Klebsiella and Proteus antigens were detected. The antigen-stimulated blast transformation of spleen lymphocytes in mice subjected to aerosol immunizations in 5 exposures was high. After subcutaneous immunization significant changes in such characteristics were detected on day 15. The data thus obtained were indicative of good prospects in the development Immunovac VP-4 as the medicinal form intended for use in aerosols.