Immunological characteristics in the therapy of atopic dermatitis in children with polycomponent vaccine Immunovac BN-4

IgE-mediated reactions linked with the polarization of the immune process towards, mainly, the activation of Th2 lymphocytes which synthesized interleukins, responsible for switching over B lymphocytes to the production of IgE, were found to be the most important mechanism of the pathogenesis of atopic dermatitis (AD). The use of immunomodulating preparations, capable of changing unbalance in the system of Th1/Th2 cells, is one of promising approaches to the complex therapy of AD. Poly-component vaccine Immunovac BN-4 was included into the complex therapy of AD in children, The dynamics of immunological characteristics was studied for the period of 6 months after the end of the course of therapy. A considerable increase in the absolute and relative amount of lymphocytes with markers CD3, CD4, CD16, CD21, CD25, a rise in the levels of IgA, IgG and a decrease in the level of total IgE in the blood serum were established. The inclusion of the polycomponent vaccine into the complex therapy of AD may be recommended.     

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.     

Classification of established atopic dermatitis in children with the in vivo imaging methods

Atopic dermatitis (AD) is a cutaneous disease resulting from a defective barrier and dysregulated immune response. The severity scoring of atopic dermatitis (SCORAD) is used to classify AD. Noninvasive imaging approaches supplementary to SCORAD were investigated. Cr:forsterite laser‐based microscopy was employed to analyze endogenous third‐harmonic generation (THG) and second‐harmonic generation (SHG) signals from skin. Imaging parameters were compared between different AD severities. Three‐dimensional reconstruction of imaged skin layers was performed. Finally, statistic models from quantitative imaging parameters were developed for predicting disease severity. Our data demonstrate that THG signal intensity of lesional skin in AD were significantly increased and was positively correlated with AD severity. Characteristic gray level co‐occurrence matrix (GLCM) values were observed in more severe AD. In the 3D reconstruction video, individual dermal papilla and obvious fibrosis in the upper papillary dermis were easily identified. Our estimation models could predict the disease severity of AD patients with an accuracy of nearly 85%. The THG signal intensity and characteristic GLCM patterns are associated with AD severity and can serve as quantitative predictive parameters. Our imaging approach can be used to identify the histopathological changes of AD objectively, and to complement the SCORAD index, thus improving the accuracy of classifying AD severity.      

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.     

Immune response following administration of multicomponent vaccine VP-4 in elderly patients

The dynamics of immunological characteristics after the administration of polycomponent vaccine B[symbol: see text]-4 to elderly persons, constituting a risk group with respect to acute respiratory diseases and exacerbations of chronic inflammatory diseases of respiratory organs, was studied. The nasal-oral administration of the vaccine induced immunological shifts in the systems of local and systemic immunity. The content of the populations of lymphocytes with markers CD3, CD4, CD16, CD20 was found to have positive dynamics. Considerable shifts in the system of local immunity were registered: the content of sIgA and IgA in the saliva greatly increased; in addition, an increase in the titers of antibodies to Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli was observed in persons with initially low titers.     

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.     

The effect of immunotherapy with the VP-4 multicomponent vaccine in children with frequent acute respiratory diseases and obstructive bronchitis

The results of prolonged observations on children with frequent acute respiratory diseases (ARD), subject to immunoprophylaxis with the use of polycomponent vaccine (VP-4), prepared from the antigens of opportunistic microorganisms, are presented. The vaccine was introduced to 30 children in 3 intranasal administrations and 6-8 oral administrations. The morbidity rate of the children was registered and their clinical status was evaluated for a year after the introduction of vaccine VP-4. As revealed in these observations, the frequency of ARD cases among the immunized children decreased 3 times or more in comparison with that among the same children, registered during a year prior to the introduction of the vaccine. In addition to a decrease in the frequency of ARD cases, a decrease in their duration and in the number of antibiotic administrations, as well as in the necessity of hospitalization, were also registered.     

Humoral immune response in patients with bronchopulmanory infections to immunotherapy

The content of IgA, IgM, IgG and the level of specific antibodies in the blood serum of patients with bronchopulmonary diseases after a course of immunotherapy with polycomponent vaccine B[symbol: see text]-4 was studied. A rise in the concentration of IgM due to the synthesis of specific antibodies to Proteus vulgaris, Escherichia coli and Klebsiella pneumoniae was found to occur. The examination of sick children revealed that a high proportion of them (54%) showed a pronounced decrease in the level of IgA. The use of the preparation made it possible to enhance the level of IgA.     

Immunostimulating activity of polycomponent vaccine "Immunovac-VP-4" and grippol after their combined administration

The experimental study of the immunostimulating activity of therapeutic bacterial polycomponent vaccine VP-4 and prophylactic vaccine grippol, introduced both separately and in combination, on mice infected with Salmonella typhimurium, used as a model. Both preparations were found to produce an immunomodulating effect. The combined subcutaneous injection of VP-4 and grippol did not decrease their immunostimulating activity, but their separate administration at an interval of 14 days resulted in essential decrease in the protective activity of each of these two preparations. As shown on the model of Klebsiella infection in mice, challenged 4 weeks after immunization, VP-4 ensured the survival of 78.6% of mice, while after the injection of grippol their survival rate was not different from that of the group of intact animals. The evaluation of the immunostimulating activity of these preparations under the conditions of the prophylaxis of influenza and acute respiratory infections in organized groups of children revealed that the use of VP-4 alone or grippol in combination with VP-4 considerably decreased the number of secondary bacterial complications in children.     

Use of loading doses of bifidumbacterin forte for treatment of patients with acute enteric infections

The clinical observation of patients with acute enteric infections (AEI), treated with loading doses of Bifidumbacterin forte during the first 2 days of the disease, was carried out. The preparation was shown to produce a positive effect on the course of AEI: salmonellosis, alimentary toxicoinfections, acute, dysentery. The early decrease of the manifestations of intoxication, pain syndrome, diarrhea, as well as the acceleration of convalescence in comparison with standard treatment, were noted. The most essential dynamics was registered in salmonellosis patients. The analysis of clinical results allowed to recommend the use of loading doses of Bifidumbacterin forte, a probiotic with high colonization potential to normalize the microbiocenosis of the intestine in AEI.     

Early-Onset Atopic Dermatitis in Children: Which Are the Phenotypes at Risk of Asthma? Results from the ORCA Cohort

Background

Atopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term “atopic march”. However, this classic sequence is not always present and only a few studies have addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma.

Methods

We performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6.

Results

We identified 3 clusters - cluster 1 (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called “AD with low sensitization”; - cluster 2 (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called “AD with multiple sensitizations” - cluster 3 (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called “AD with familial history of asthma”. Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p<0.01).

Conclusion

Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma.     

Protective efficacy of combined administration of the multicomponent vaccine and the immunomodulator myelopid in experimental infections in mice

The influence of myelopid (MP) on the protective activity of polycomponent vaccine VP-4 prepared from the antigens of opportunistic bacteria was studied on experimental infections of mice, caused by Klebsiella pneumoniae, Salmonella typhimurium and Staphylococcus aureus. In staphylococcal and Klebsiella infections the joint administration of vaccine VP-4 and MP produced more pronounced protective effect than each of these preparations, introduced alone. The protective action of vaccine VP-4 was specially enforced by MP in cases of local staphylococcal infection. Recommendations on the joint use of two or more immunomodulating agents are possible only on the basis of the experimental substantiation of their effect in definite infections.     

Use of therapeutic polycomponent vaccine "Immunovac VP-4" for the treatment of chronic bacterial prostatitis

A complex of clinical and laboratory examinations of patients with bacterial chronic prostatitis was carried out. The patients were divided into two groups: 55 patients treated by the method of immunotherapy and 20 patients (controls) undergoing basic therapy. Immunotherapy was carried out with the use of polycomponent vaccine VP-4 containing Staphylococcus aureus, Klebsiella pneumoniae, Proteus vulgaris and Escherichia coli antigens. Vaccinal therapy was indicated in cases with infection focus associated with opportunistic bacteria, a prolonged torpid course of prostatitis and when different schemes of etiotropic therapy proved to be ineffective. The vaccine was introduced in 4 or 5 subcutaneous injections at an interval of 5-7 days. The study revealed that in cases of chronic prostatitis accompanied by microecological and immune disturbances the use of complex therapy allowed to achieve good clinical and laboratory results in 91% of the patients. In the patients undergoing immunotherapy the elimination of opportunistic bacteria from the urogenital tract and the restoration of affected microflora occurred.     

The relationship between serum levels of total IgE, IL-18, IL-12, IFN-gamma and disease severity in children with atopic dermatitis

Studies about the role of cytokines on the immunopathogenesis of atopic dermatitis (AD) are generally based on in vitro observations and this role has not been completely clarified yet. Serum levels of total IgE, IL-18, IL-12, IFN-gamma and the relationship between these parameters and disease severity, determined using the SCORAD index, in a group of atopic patients were investigated in this study. Serum levels of total IgE were measured by the nephelometric method and serum levels of IL-18, IL-12/p40 and IFN-gamma were measured by ELISA method. Serum levels of total IgE and IL-18 were found significantly higher in study group than in controls (P<.001). There was no statistically significant difference between patients and controls in respect of serum levels of IL-12/p40 (P = .227). A statistically significant relationship between SCORAD values and serum levels of total IgE (P < .001), IL-18 (P < .001), and IL-12/p40 (P < .001) was determined. These results show that serum levels of IL-18 can be a sensitive parameter that importantly correlates with clinical severity of AD, can play a role in the immunopathogenesis of AD, and furthermore may be used in the diagnosis and follow-up of the disease in addition to other parameters.     

不同严重程度儿童特应性皮炎血清半乳糖凝集素-10及炎症因子的表达水平及其与皮肤感染的相关性分析

摘要 目的：分析不同严重程度儿童特应性皮炎血清半乳糖凝集素-10（Gal-10）及炎症因子的表达水平及其与皮肤感染的相关性。方法：选择我院自2022年1月至2023年1月收治的110例特应性皮炎患儿纳入观察组,根据特应性皮炎评分（SCORAD）,分为轻度组、中度组和重度组;另选110例健康体检儿童纳入对照组。检测所有入选者血清Gal-10、炎症因子（IL-4、IL-13、IL-31）水平及不同部位皮肤经皮失水量,分析血清Gal-10、IL-4、IL-13、IL-31与SCORAD评分、不同部位皮肤经皮失水量的关系,使用受试者工作特征曲线（ROC）分析血清Gal-10、炎症因子（IL-4、IL-13、IL-31）对皮肤感染的预测效能。结果：观察组血清Gal-10、IL-4、IL-13、IL-31水平均高于对照组（P＜0.05）;随着儿童特应性皮炎病情加重,患儿血清Gal-10、IL-4、IL-13、IL-31水平随之升高,血清Gal-10、IL-4、IL-13、IL-31水平在轻度组、中度组和重度组中差异显著（P＜0.05）;经Pearson相关性分析,特应性皮炎患儿血清Gal-10、IL-4、IL-13、IL-31水平与SCORAD评分,前壁伸侧、前壁屈侧、脸颊及胫前的经皮失水量呈正相关（P＜0.05）;在110例特应性皮炎患儿中,发生皮肤感染43例;经ROC曲线分析,血清Gal-10、IL-4、IL-13联合IL-31预测特应性皮炎患儿发生皮肤感染的敏感度为89.72%、特异度为56.97%、ROC曲线下面积（AUC）为0.921。结论：血清Gal-10、炎症因子（IL-4、IL-13、IL-31）水平与儿童特应性皮炎严重程度有显著相关性,对于评估其皮肤屏障功能和预测皮肤感染均具有一定作用,值得临床予以重视应用。     

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.     

Intensity of the epidemic process of whooping cough under conditions of mass immunization over a period of many years

On the basis of analysis of whooping cough incidence in 1959 to 1975 in Moscow the authors present characteristics of the epidemic process under conditions of planned many-year immunization of children against this infection. Whooping cough morbidity proved to undergo significant changes-from sharp falls the first 8 years of immunization to a relative stabilization with a gradual reduction the last 5 years. Marked seasonal and periodic elevations persist against the background of reduction of morbidity. Preschool- and schoolchildren are equally involved in the epidemic process; the most frequently involved are nonvaccinated children aged 1 year and 4 to 10 years, which lost postvaccinal immunity. Further reduction of the severity of whooping cough and increase in the number of unimanifested forms of the infection was noted. This was apparently connected not only with immunization, but also with the reduction of the virulence of H. pertusis detected in studying the cultures isolated in Moscow from 1967 to 1974. The intensity indices of the epidemic process in whooping cough pointed to the necessity of using a more effective vaccine for the protection of children from whooping cough, despite the noted reduction of morbidity, and diminished severity of the course of the disease, and of the causative agent virulence.     

Approaches to prevention and treatment of latex allergy

Data on sensitization to latex as well as measures aimed at prevention and treatment of latex allergy, are presented. The intensity of the symptoms manifestation of latex allergy was shown to depend on the duration of contact with latex. To prevent the development of latex allergy, the following preparations were used: the antihistaminic preparation Claritine, the immunocorrecting preparations Ruzam and polycomponent vaccine VP-4. The use of Claritine was shown to lead to the alleviation of the symptoms of latex allergy, but after treatment with Claritine was stopped the symptoms of latex allergy reappeared. The clinical effect lasted for as long as 2 months after treatment with Ruzam, while in case of polycomponent vaccine VP-4 use remission was registered even 3 months later. The data presented thus confirm topicality of the latex allergy problem and practical importance of using the immunocorrecting preparations Ruzam and polycomponent vaccine VP-4 for its prevention and treatment.     

Assessment of effect of vaccination against pneumococcal infection in children with chronic renal failure and glomerulonephritis

Clinical effect and immune response to vaccination with PNEUMO 23 vaccine was assessed in 18 children with chronic renal failure (CRF) and 40 children with different forms of glomerulonephritis (GN) aged 2 - 15 years. Control group was comprised by nonvaccinated patients (16 patients with CRF; 20 -with GN). Children from two groups were comparable on age and severity of disease's course. Local adverse reactions with duration not longer than 2 days were registered in 22% of vaccinees with CRF, and in 20% of vaccinees with GN. Mild and moderate systemic reactions were registered in 11% and 7.5% of recipients respectively. 1 month after vaccination significant 2.5 - 3.2-fold increase of antibodies concentration was detected in all groups irrespective from nosology and previous treatment. Two-fold increase of concentration of antibodies was observed in 64% and 61% of children with GN and CRF respectively. Clinical effect of vaccination appeared as 2.9-fold decrease of acute respiratory disease (ARD) incidence. Demand in antibacterial therapy decreased by 6.4-fold. Duration of ARD and course of antibacterial treatment decreased by 2.2 and 3 times respectively. Proportion of GN exacerbations related to infecvion decreased from 39% before vaccination to 8% after vaccination. In the control group this proportion did not change (50% and 45% respectively). Vaccine efficacy index was 2.13, coefficient of efficacy - 53.1%.     

Prebiotics Do Not Influence the Severity of Atopic Dermatitis in Infants: A Randomised Controlled Trial

The objective was to evaluate the effects of a hypoallergenic (HA) formula supplemented with prebiotic galacto-oligosaccharides on the severity of atopic manifestations. A randomised clinical trial was conducted. The control group was infants, fed with hypoallergenic formula and without supplementation. The duration of the study was six months. The primary outcome of the study was a difference in the severity of atopic dermatitis measured using SCORAD (Scoring Atopic Dermatitis) criteria. Secondary outcomes were anthropometry (length, weight, and head circumference), together with the tolerance and incidence of infections. Both groups showed a decrease of average SCORAD values, but no statistically significant difference between the evaluated groups was observed. There were no statistically significant differences in anthropometry, or the tolerance or incidence of infections. Although there is no evidence, that consumption of a hypoallergenic infant formula enriched with prebiotic galacto-oligosaccharides had any effect on SCORAD, it was safe and well tolerated.

Trial Registration

www.clinicaltrials.gov NCT 02077088