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Mucosal immunity plays a major role not only in the prevention but probably also in the outcomes of COVID-19. An enhanced production of secretory immunoglobulin A (sIgA) might contribute to the activation of the immune response mechanisms. To assess the levels of sIgA produced by epithelial cells in the nasal and pharyngeal mucosa and those measured in salivary gland secretions and to study the course of COVID-19 following the combined scheme of intranasal and subcutaneous administration of a bacteria-based immunostimulant agent. This study included 69 patients, aged between 18 and 60, who had moderate COVID-19 infection. They were divided into two groups: Group 1 (control group) included 39 patients who received only background therapy, and Group 2 was made up of 30 patients who received background therapy in combination with the Immunovac VP4 vaccine, a bacteria-based immunostimulant agent, which was given for 11 days starting from the day of admission to hospital. The levels of sIgA were measured by ELISA in epithelial, nasal and pharyngeal swabs, and salivary gland secretions at baseline and on days 14 and 30. The combined scheme of intranasal and subcutaneous administration of the Immunovac VP4 vaccine in the complex therapy of patients with COVID-19 is accompanied by increased synthesis of sIgA in nasal and pharyngeal swabs, more intense decrease in the level of C-reactive protein (CRP) and reduction in the duration of fever and length of hospitalization compared to the control group. Prescribing a immunostimulant agent containing bacterial ligands in complex therapy for COVID-19 patients helps to enhance mucosal immunity and improves the course of the disease.
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Adjuvantes Imunológicos , COVID-19 , Imunoglobulina A Secretora , SARS-CoV-2 , Humanos , Imunoglobulina A Secretora/imunologia , COVID-19/imunologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Adjuvantes Imunológicos/administração & dosagem , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunidade nas Mucosas/efeitos dos fármacos , Adulto Jovem , Adolescente , Administração IntranasalRESUMO
PURPOSE: Understanding the relationship between patient immune characteristics, disease severity, and mortality represents a critical step in the fight against COVID-19. Elevated levels of programmed death ligand-1 (PD-L1) and Neutrophil-lymphocyte ratio (NLR) are linked to increased severity of acute COVID-19 in patients. This study aimed to investigate the association of the combination of sPD-L1 and NLR with 1-year Mortality in patients with COVID-19. METHODS: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of sPD-L1 in the blood serum was evaluated by ELISA. The effect of biomarkers on the development of mortality was analyzed with multivariate regression. RESULTS: The risk of mortality within one year HR was 2.46 if the plasma sPD-L1 value of more than 277.13 pg/ml, and for NLR more than 2.46 HR was 2.87. The model of combining sPD-L1 and NLR resulted in an improvement in the predictive accuracy of the Hazard Ratio 7.6 (95 % CI: 3.02-19.11). CONCLUSION: The combination of two immune-mediated markers (sPD-L1 and NLR), which reflect the systemic inflammatory balance of activation and exhaustion, can complement each other and improve the assessment of the risk of death in patients with COVID-19.
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COVID-19 , Neutrófilos , Humanos , Antígeno B7-H1 , Biomarcadores , Linfócitos , Prognóstico , Estudos ProspectivosRESUMO
Aim: Current problem related to COVID-19 is various complications after disease, especially long-term mortality after COVID-19. Routine blood tests presented their effectiveness in the diagnosis, prognosis and mortality of COVID-19. The neutrophil-to-lymphocyte ratio (NLR) is an important marker of systemic inflammation. Soluble Trigger receptor expressed on myeloid cells-1 (sTREM-1) is considered an intrinsic enhancer of inflammatory signals. This study examined the predictive value of these markers in COVID-19 mortality. Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The neutrophil-to-lymphocyte ratio (NLR) was calculated as the absolute number of neutrophils divided by the absolute number of lymphocytes. The level of sTREM-1 in the blood serum was evaluated by ELISA. Results: Plasma sTREM-1 concentration greater than 59.08 pg/mL and an NLR greater than 2.29 had an increased risk of early mortality (hazard ratio = 8.07; 95% CI: 1.03-62.17 and 9.24; 95% CI: 1.202-71.08, respectively); for long-term mortality of sTREM-1 greater than 47.34 pg/mL (hazard ratio = 7.96; 95% CI: 1.072-59.18) and NLR greater than 2.10 (hazard ratio = 11.52; 95% CI: 1.551-85.52). Conclusion: This study suggests that early levels of sTREM-1 and NLR are associated with the risk of 6-month mortality after experiencing COVID-19.
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BACKGROUND: for the first time, the effect of one and two doses of adjuvanted influenza vaccines on toll-like receptors (TLRs) in patients with common variable immunodeficiency (CVID) was studied and compared (primary vaccination with one vs. two doses, primary vs. repeated vaccination). MATERIALS AND METHODS: Six patients received one dose of quadrivalent adjuvanted influenza vaccine during the 2018-2019 and 2019-2020 influenza seasons, and nine patients with CVID received two doses of trivalent inactivated influenza vaccine during 2019-2020. Expression of TLRs was measured by flow cytometry. RESULTS: The expression of toll-like receptors in patients with CVID was noted both with repeated (annual) administration of the influenza vaccine and in most cases was accompanied by an increase in the proportion of granulocytes (TLR3 and TLR9), lymphocytes (TLR3 and TLR8), and monocytes (TLR3 and TLR9). When carried out for the first time as a simultaneous vaccination with two doses it was accompanied by an increase in the proportion of granulocytes, lymphocytes expressing TLR9, and on monocytes-TLR3 and TLR9. CONCLUSION: in CVID patients, the use of adjuvanted vaccines is promising, and research on the influence of the innate immunity and more effective regimens should be continued.
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Imunodeficiência de Variável Comum , Vacinas contra Influenza , Influenza Humana , Humanos , Imunodeficiência de Variável Comum/induzido quimicamente , Influenza Humana/prevenção & controle , Receptor 3 Toll-Like , Receptor Toll-Like 9 , Receptores Toll-Like , Adjuvantes Imunológicos , VacinaçãoRESUMO
Measles has not yet been eradicated; therefore, its outbreaks are still reported throughout the world. Like any infection, measles is dangerous for immunocompromised patients. Levels of anti-measles IgG antibodies were measured in 157 patients aged 17 to 72, who were placed on the lung transplant waiting list. Measurements were undertaken by enzyme-linked immunosorbent assay (ELISA) using the VectoMeasles-IgG kit (Russia). The proportion of patients seronegative for measles was 19% (30/157). Correlation was detected between patients' age and their levels of anti-measles antibodies, with higher proportions of patients having undetectable titers (25.5-28.9%) or low antibody levels (38.3-44.4%) in the young age groups (17-29 and 30-39 years old). There were no differences between male and female patients in levels of anti-measles antibodies or in the proportion of seronegative individuals. Analyses of antibody levels with regard to type of disease revealed the highest rate of seronegative results in cystic fibrosis patients (34.4%, 11/32). Overall, 19% of lung transplant candidates, mostly young people and cystic fibrosis patients, did not have protective immunity against measles.
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Fibrose Cística , Transplante de Pulmão , Sarampo , Humanos , Masculino , Feminino , Adolescente , Anticorpos Antivirais , Sarampo/epidemiologia , Vírus do Sarampo , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina GRESUMO
Background: This study investigates the efficiency of two different types of immunomodulators for the treatment of non-severe community-acquired pneumonia (CAP) and assesses their long-term effects. Methods: The study included 55 patients with non-severe CAP. Group 1 (control) received only standard CAP therapy; the other two groups received immunomodulators simultaneously with the standard therapy: bacterial lysate for group 2 and azoximer bromide (AzB) for group 3. TNF and IL-6 concentrations were determined on the day of hospitalization as well as on days 13 and 60 of follow-up. For 2 years, we monitored the incidence of low respiratory tract infections (LRTIs) in the same patients with CAP (n=55). Results: The overall duration of all symptoms was lower in the immunomodulator groups compared with the control group. During treatment, TNF and IL-6 concentrations decreased on days 13 and 60 in all patients; in patients who received immunomodulators, TNF and IL-6 were reliably lower than in control patients. IL-6 concentration decreased on day 60 in the bacterial lysate and AzB treatment groups and did not differ (p=0.72). The odds ratio for the development of LRTIs in the AzB group was 0.15 (0.02-0.93) (p=0.04), suggesting its protective effect. Conclusion: Inclusion of immunomodulators in the basic treatment of non-severe CAP reduces the duration of symptoms and is associated with improvement of the pro-inflammatory cytokine profile. In 2 years of follow-up, the long-term effects of the immunomodulatory therapy showed a statistically significant lower incidence of LRTIs in the AzB group only. However, given the small sample size of this study, further clinical studies are needed.
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Background: Although extensive research has been conducted on the role of local immunity in patients with SARS-CoV-2, little is known about the production and concentrations of secretory IgA (SIgA) in different mucosal compartments. This article aims to assess the secretion of SIgA in the nasal and pharyngeal compartments and saliva of patients with COVID-19 and to investigate the possibility and efficiency of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms. Methods: This study included 78 inpatients, aged between 18 and 60 years, who had confirmed COVID-19 with moderate lung involvement. The control group (n=45) received basic therapy, and the treatment group (n=33) was additionally administered the bacteria-based pharmaceutical Immunovac VP4 from day 1 to day 10 of hospitalization. SIgA levels were measured by ELISA at baseline and on days 14 and 30. Results: No systemic or local reactions associated with Immunovac VP4 were reported. We observed a statistically significant reduction in the duration of fever and hospitalization in patients who received Immunovac VP4 compared with those from the control group (p=0.03 and p=0.05, respectively). Changes over time in SIgA levels in nasal swabs were found to be significantly different in the two treatment groups (F=7.9, p[78.0]<0.001). On day 14 of observation, patients in the control group showed a statistically significant reduction in SIgA levels from baseline (p=0.02), whereas patients in the Immunovac VP4 group had stable SIgA levels (p=0.07). On day 30 after the start of treatment, there was a statistically significant increase in SIgA levels in the Immunovac VP4 group compared with baseline (from 77.7 (40.5-98.7) µg/L to 113.4 (39.8-156.7) µg/L; p=0.05) and the levels measured on day 14 (from 60.2 (23.3-102.9) µg/L to 113.4 (39.8-156.7) µg/L; p=0.03). The control group showed a statistically significant decrease in levels of nasal SIgA (to 37.3) on day 30 (p=0.007 for comparison with baseline values and p=0.04 for comparison with levels measured on day 14). Changes over time in SIgA levels measured in pharyngeal swabs were also different between the two treatment groups, and this difference reached statistical significance (F=6.5, p[73.0]=0.003). In the control group, this parameter did not change throughout the study (p=0.17 for a comparison between the levels measured on day 14 and the baseline values, and p=0.12 for a comparison between the levels measured on day 30 and the baseline values). In the Immunovac VP4 group, there was a statistically significant increase from baseline in SIgA levels on study day 30: from 1.5 (0.2-16.5) µg/L to 29.8 (3.6-106.8) µg/L (p=0.02). Changes over time in salivary SIgA did not show a significant difference between study groups (F=0.3, p[66.3]=0.75). Conclusion: As part of combination therapy, the bacteria-based immunostimulant agent Immunovac VP4 increases SIgA levels in the nasal and pharyngeal compartments and induces clinical improvement. Induced mucosal immunity is central to the prevention of respiratory infections, particularly in patients with post-COVID-19 syndrome.
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Coronavirus disease (COVID-19) has generated interest in the assessment of systemic immune status, but existing knowledge about mucosal immunity is clearly insufficient to understand the full pathogenetic mechanisms of the disease. The aim of this study was to evaluate the long-term effects of novel coronavirus infection on mucosal immunity in the postinfection period among health care workers (HCWs). A total of 180 health care workers with and without a history of COVID-19 who ranged in age from 18 to 65 years were enrolled in this one-stage, cross-sectional study. The study subjects completed the 36-Item Short Form (36) Health Survey (SF-36) and the Fatigue Assessment Scale. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, and nasopharyngeal and oropharyngeal scrapings by an enzyme-linked immunosorbent assay. Specific anti-SARS-CoV-2 IgG antibodies were quantified in serum samples by chemiluminescence immunoassay. Analysis of the questionnaire data showed that all HCWs with a history of COVID-19 reported health problems that limited their daily activities and negative changes in their emotional health three months after the disease, regardless of its severity. The following shifts were detected in the adaptive arm of the immune response in different mucosal compartments. Among subjects who had severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p < 0.05 and p < 0.005, respectively). Compared to the subjects in the control group, all subjects with prior COVID-19 had significantly higher levels of total IgG in induced sputum. In the group of patients who had had severe infection, total IgG in saliva was also higher (p < 0.05). A direct statistically significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum. A significant correlation was observed between total IgG levels and the parameters of physical and social activities, mental health, and fatigue levels. Our study demonstrated long-term changes in the humoral mucosal immune response, which were most pronounced in health care workers with a history of severe or moderate-to-severe COVID-19, and an association of these changes with certain clinical signs of post-COVID-19 syndrome.
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COVID-19 , Pessoal de Saúde , Imunidade nas Mucosas , Federação Russa , COVID-19/imunologia , COVID-19/patologia , COVID-19/fisiopatologia , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Imunoglobulina A/análise , Sistema Respiratório/imunologia , Anticorpos Antivirais/análise , Índice de Gravidade de Doença , Imunoglobulina G/análise , SARS-CoV-2/fisiologiaRESUMO
Background: Studies aimed at identifying the mechanisms of the immunoregulatory effect of vaccination with diphtheria and tetanus toxoid on the parameters of adaptive immunity in children with kidney pathology are limited. The study aimed to study the effect of revaccination against diphtheria and tetanus on the proliferation and differentiation of immunocompetent cells, the formation of specific antibodies, and the course of the disease in children with glomerulonephritis (GN). Methods: The study included 45 children with glomerulonephritis (GN) aged 5 to 15 years, in remission from 6 months up to 4 years. Of these, 25 children were revaccinated with DT toxoid (Diphtheria-Tetanus toxoid with reduced antigenic content) and 20 were in the control group (not vaccinated). The frequency of development of local and systemic reactions and the course of GN were assessed. The subpopulation structure of lymphocytes was studied in dynamics after 1-6-12 months by flow cytometry and IgG levels to diphtheria and tetanus were studied by ELISA. Results: In 92% of children with GN, the post-vaccination period was uneventful. 8% showed a rise in temperature up to 37.3°C, without the development of local reactions. During the year, none of the patients had an exacerbation of GN or a concomitant disease. After revaccination with DT toxoid, a significant increase in IgG antibodies against diphtheria and tetanus was revealed, which persisted after 12 months - 7.5 [5.1-10.8] IU/mL (p <0.001) and 7.2 [4.8-10.7] IU/mL (p <0.001), respectively. In the post-vaccination period, a multidirectional change in the concentration of T-lymphocytes was noted: with an initially increased level, their percentage after revaccination with DT toxoid decreases from 83 (81-86) % to 78 (76-80)% after a month (p = 0.04) and up to 75 (69-79)% after 12 months (p<0.001). In the control group, such a decrease was not observed. A similar picture was observed for T-helpers, cytotoxic T-lymphocytes, and in patients with an initially low percentage of cytotoxic T-lymphocytes, on the contrary, its increase was noted (p<0.001), which is comparable with the value of this parameter in the group of children with initially normal value (H = 0.54, p = 0.76). The same patterns were observed in the change in the content of B-cells: one month after revaccination, the relative level of B-cells in patients with an initially lowered value increased (p = 0.02) and remained for 12 months (p<0.001). Conclusion: Revaccination with DT toxoid in children with GN not only does not cause undesirable changes in the system of immunocompetent cells but also has an immunomodulatory effect, which contributes to the favorable maintenance of the remission period of the disease.
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Glomerulonefrite/imunologia , Imunomodulação , Toxoide Tetânico/imunologia , Adolescente , Fatores Etários , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Feminino , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Glomerulonefrite/terapia , Humanos , Imunidade , Imunização Secundária , Imunoglobulina G/imunologia , Contagem de Linfócitos , Masculino , Linfócitos T/imunologia , Linfócitos T/metabolismo , Toxoide Tetânico/administração & dosagem , VacinaçãoRESUMO
It has been proven that post-vaccination immunity to measles virus after two doses of vaccine is not able to persistently protect against infection throughout life. The goal of this research was to determine the immune layer to the measles virus among women in labor and maternity ward personnel in the same medical institution. The levels of IgG antibodies to measles virus in the umbilical cord blood of 594 women in labor and 88 workers of the maternity ward were studied by ELISA. It was revealed that 22.7% of umbilical cord blood serum samples from parturient women and 21.4% of blood serum samples from maternity ward personnel were seronegative (<0.18 IU/ml). Levels of IgG antibodies to measles virus in low values (<1.0 IU/ml) were detected in 67% of blood serum samples among women in labor and 68.9% among employees of the maternity ward. Among women in labor, women under 35 years of age are at the highest risk of contracting measles; the proportion of women with low levels of protective antibodies in this age group was almost 70%, and the proportion of women without protective levels of antibodies was 23%. Compared with the age group 36-43, the age of women in labor under 35 was associated with a higher chance of not having immune protection against infection with measles virus OR [95% CI] = 2.2 [1.1-4.5] (p = 0.02) or had a low level of protection OR [95% CI] = 1.9 [1.2-3.0] (p = 0.001). It was also found that among women over 35 years of age, the proportion of persons with a high level of antibodies in women in labor was statistically significantly higher than among members of the maternity ward staff (13 and 0%, respectively, p = 0.007). Thus, maternity ward employees and women in labor constitute a risk group for measles due to the presence of a high proportion of seronegative persons among women of childbearing age (both maternity ward employees and women in labor). These conditions create the need to revise current approaches to present vaccination procedures, especially in the current epidemiological situation with COVID-19.
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Anticorpos Antivirais/sangue , Vírus do Sarampo/imunologia , Sarampo/prevenção & controle , Unidade Hospitalar de Ginecologia e Obstetrícia/estatística & dados numéricos , Adulto , Distribuição por Idade , Feminino , Pessoal de Saúde , Humanos , Imunoglobulina G/sangue , Sarampo/sangue , Vacina contra Sarampo/imunologia , Pessoa de Meia-Idade , Gravidez , Adulto JovemRESUMO
Early studies on vaccination of children with oncological diseases were only dedicated to the assessment of safety and immunogenicity of the drug. Mechanisms of the post-vaccination immune response were not investigated. This study involved 41 patients aged 7-15 years who were treated for solid tumors two or more years ago. Of these, 26 were vaccinated against diphtheria and tetanus with ADS-m toxoid. Fifteen children (i.e., controls) were not vaccinated. The vaccination tolerability and clinical characteristics of the underlying disease remission ware assessed. Lymphocyte subpopulations were investigated over time by flow cytometry at 1, 6, and 12 months. IgG anti-diphtheria and anti-tetanus toxoids levels were assessed by ELISA. Within the first day of the post-vaccination period, two (7.7%) children demonstrated moderate local reactions and increased body temperature (up to 38.0°C). Relapse and metastasis were not mentioned within a year after immunization. An increase in concentration of IgG antibodies, maintained for 12 months, were noted [2.1 (1.3-3.4) IU/ml against diphtheria (p <0.001), 6.4 (2.3-9.7) IU/ml against tetanus (p <0.001)]. In contrast to healthy children, those with a history of cancer demonstrated a decrease in the relative number of mature T lymphocytes, as well as in absolute number of cytotoxic T cells and B lymphocytes. In a month after the revaccination, a significant increase in absolute (p = 0.04) and relative (p = 0.007) numbers of T lymphocytes and T helpers was revealed. In a year, these values decreased to baseline levels. As for helpers, they decreased below baseline and control values (p = 0.004). In a year after the vaccination, there was a significant (p = 0.05) increase in lymphocyte level with a decrease in the number of NK cells and B cells as compared with controls. Revaccination against diphtheria and tetanus promoted proliferation of a total lymphocytic cell pool along with restoration of the T lymphocyte subpopulation in children with a history of solid tumors. The ADS-m toxoid has a certain nonspecific immunomodulatory effect. These findings are important, also in the midst of the coronavirus pandemic.
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Imunidade Adaptativa/imunologia , Vacina contra Difteria e Tétano/imunologia , Neoplasias/imunologia , Vacinação , Adolescente , Anticorpos Antibacterianos/imunologia , Criança , Difteria/imunologia , Difteria/prevenção & controle , Vacina contra Difteria e Tétano/administração & dosagem , Humanos , Imunização Secundária , Subpopulações de Linfócitos/imunologia , Linfócitos/imunologia , Neoplasias/patologia , Federação Russa , Tétano/imunologia , Tétano/prevenção & controleRESUMO
BACKGROUND: Influenza prophylaxis with the use of quadrivalent vaccines (QIV) is increasingly being introduced into healthcare practice. METHODS: In total, 32 healthy adults and 6 patients with common variable immunodeficiency (CVID) received adjuvant QIV during 2018-2019 influenza season. Depending on initial antibody titers, healthy volunteers were divided into seronegative (≤1:20) and seropositive (≥1:40). To evaluate immunogenicity hemagglutination inhibition assay was used. RESULTS: All participants completed the study without developing serious post-vaccination reactions. Analysis of antibody titer 3 weeks after immunization in healthy participants showed that seroprotection, seroconversion levels, GMR and GMT for strains A/H1N1, A/H3N2 and B/Colorado, B/Phuket among initially seronegative and seropositive participants meet the criterion of CHMP effectiveness. CVID patients showed increase in post-vaccination antibody titer without reaching conditionally protective antibody levels. CONCLUSION: Adjuvant QIV promotes formation of specific immunity to vaccine strains, regardless of antibodies' presence or absence before. In CVID patients search of new regimens should be continued.
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Background: Recent addition to vaccines of adjuvants has been actively used to enhance the immunogenicity. However, the use of adjuvants for the development of quadrivalent inactivated influenza vaccines (QIV) is currently limited. The aim of this study was to examine immunogenicity of adjuvanted QIV in healthy people and patients with primary immune deficiency-common variable immune deficiency (CVID). Methods: In total before the flu season 2018-2019 in the study were involved 32 healthy volunteers aged 18-52 years and 6 patients with a confirmed diagnosis of CVID aged 18-45 years. To evaluate antibody titers 21 days after vaccination against the influenza A and B strains a hemagglutination inhibition assay (HI) was used. Results: In healthy volunteers adjuvanted QIV has proved its immunogenicity to strains A/H1N1, A/H3N2, B/Phuket and B/Colorado in seroprotection (90, 97, 86, and 66%, respectively), seroconversion (50, 60, 52, and 45%, respectively), GMR (6.2, 5.7, 4.2, and 3.4, respectively). Statistically significant differences in the level of all criteria were revealed between groups of healthy and CVID patients regardless of the virus strain. Most patients with CVID showed an increase in post-vaccination antibody titer without reaching conditionally protective antibody levels. Conclusion: Immunization with single dose of adjuvanted QIV with decreased amount of hemagglutinin protein to all virus strains due to the use of azoximer bromide forms protective immunity in healthy people, but in patients with CVID the search for new vaccination schemes is the subject of further investigations, as well as the effectiveness of boosterization with adjuvant vaccines.
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Imunodeficiência de Variável Comum , Imunogenicidade da Vacina/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Adulto , Anticorpos Antivirais/imunologia , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Masculino , Pessoa de Meia-Idade , Vacinas Combinadas/imunologiaRESUMO
Background: In the last decade, adjuvant-containing vaccines, exerting different effects on the immune system, including the production of cytokines, which are one of the most important regulatory systems of the body, are introduced into practice. Objectives: An effect of the immunoadjuvant polymer-subunit and adjuvant-free vaccines against influenza on the cytokine profile of mononuclear leukocytes in 27 healthy women was studied. Methods: The study of cytokine profile in human peripheral blood mononuclear leukocytes exposed to vaccines against influenza virus was determined by flow cytometry method (Cytomix FC-500, Beckman Coulter, USA) using the Multiplex-13 test system (Bender MedSystems, Austria). Results: It was established that all the studied vaccines leaded to somewhat increased levels of Th1/Th2/Th17/Th9/Th22 cytokines in the culture fluid of peripheral blood mononuclear leukocytes (PBML), which indicates the activation of both humoral and cellular immunity. An immunoadjuvant vaccine has been shown to be superior in activating the synthesis of Th1 (IL-12, INF-g, IL-2, IL-6, IL-1ß, TNF-α) cytokines, IL-9 and IL-22, while the subunit vaccine was superior in activating the synthesis of IL-4, and split vaccine-of IL-5. Conclusions: Immunoadjuvant vaccine is superior in terms of inducing cellular immune effectors to a greater extent compared to subunit and split vaccines.
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Adjuvantes Imunológicos/farmacologia , Citocinas/imunologia , Vacinas contra Influenza/imunologia , Leucócitos Mononucleares/imunologia , Adulto , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/prevenção & controle , Piperazinas/imunologia , Piperazinas/farmacologia , Polímeros/farmacologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
Pregnant women are risk group for influenza infection. Results of new subunit vaccines application have not been studied enough. Prospective, randomized, open-label comparative study of subunit (Agrippal) and polymeric subunit (Grippol plus) vaccines. 42 pairs of mothers-infants were participated in the study. Protective antibodies (≥ 1:40) to different influenza strains were registered on day 1 after the birth on the same level as 53% of cases in pairs mothers-infants after immune adjuvant polymeric subunit and subunit vaccines administration. There were the same level of protective antibodies (AB) among mothers after 3 month, but transplacental antibodies decreased among infants and registered in the 13-22% cases of Grippol plus group and 31-43% cases in Agrippal S1 group. AB titre to influenza virus A/H1N1/pdm09 and A/H3N2/in pairs mothers-infants were the same in both groups in first days after birth, but AB levels to B strain were lower among infants without regard to vaccine. There is no difference in AB titres among infants of both groups at 3 month of age, but their levels were twice lower versus initial data. An immune adjuvant polymeric subunit as well as subunit vaccines application in pregnant women forms protective AB in pairs mothers-infants.
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Pregnancy is a condition of modulated immune suppression, so this group of patients has increased risk of infectious diseases. Trivalent subunit vaccines, unadjusted Agrippal S1 (group I) and immunoadjuvant Grippol Plus (group II), containing 5â µg of actual influenza virus strains, were administered respectively to 37 and 42 women in the second and third trimester of physiological pregnancy. The administration of subunit influenza vaccines was accompanied by the development of local reactions in no more than 10% of patients, compared with 4.9% of the 41 pregnant women in the placebo group (group III). Systemic reactions were of a general somatic nature, did not differ between vaccinated and placebo groups, and were not associated with vaccination. Physiological births in groups I, II and III were 94.6%, 92.9% and 85.4%, respectively, and the birth rates of children without pathologies were 91.9%, 90.5% and 80.5%, respectively, and were comparable between groups. Vaccination stimulated the production of protective antibodies against influenza virus strains in 64.8-94.5% of patients after immunisation with an unadjusted vaccine and in 72.5-90.0% of patients after the administration of an immunoadjuvant vaccine. After 9â months, antibody levels were recorded in 51.3-72.9% in group I and 54.2-74.2% in group II. Immunisation against influenza in pregnant women provided a high level of seroprotection and seroconversion. Nevertheless, the level of seroprotection against the influenza strain A(H3N2, Victoria) was slightly lower in the group immunised with an unadjusted vaccine compared to those vaccinated with the immunoadjuvant vaccine.