Expression of Toll-like Receptors on the Immune Cells in Patients with Common Variable Immune Deficiency after Different Schemes of Influenza Vaccination.

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.

Nonspecific Regulation of the Number of Immunocompetent Cells Under the Influence of DT Toxoid in Children With Glomerulonephritis.

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.

Cytokine Profile in Human Peripheral Blood Mononuclear Leukocytes Exposed to Immunoadjuvant and Adjuvant-Free Vaccines Against Influenza.

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.

Assessment of Immunogenicity of Adjuvanted Quadrivalent Inactivated Influenza Vaccine in Healthy People and Patients With Common Variable Immune Deficiency.

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.

Prospective randomized open-label comparative study of immunogenicity after subunit and polymeric subunit influenza vaccines administration among mothers and infants.

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.