ASSOCIATION BETWEEN VITAMIN D-BINDING PROTEIN (VDBP) GENE POLYMORPHISM AND VITAMIN D STATUS IN YOUNG CHILDREN

Object of the research: VDBP gene polymorphism. Problem being addressed: the effect of existing polymorphic variants of the VDBP gene on the absorption of vitamin D in young children. The main scientific results. At the beginning of the survey, vitamin D supplementation was performed in 50.0±9.1 % (15/30) of children. The concentration of 25 (OH) D in the serum of the subjects was 32.9 ng/ml (23.2–60.0). All patients with the GG rs 7041 genotype of the VDBP gene had a concentration of 25 (OH) D in the range of 20-100 ng/ml, which is statistically more common than in children with the AA rs 4588 genotype (p=0.015), GT rs 7041 genotype (p=0.047) and genotype TT rs 7041 (p=0.033). Patients with CA rs 4588 genotypes – 23.7 ng/ml (14.8-35.8) and GT rs 7041 – 28.1 ng/ml (17.1–49) had the lowest serum levels of 25 (OH) D, the highest levels of 25 (OH) D – children with genotype AA rs 4588 – 122.6 ng/ml (23.2–124.1) and genotype TT rs 7041 – 78.6 ng/ml (23.2 –124.1). Carriers of the AA rs 4588 genotype were more likely than patients with the GG rs 7041 genotype to show dangerously high levels of 25 (OH) D (p=0.069). Patients with the AA rs 4588 genotype had lower alkaline phosphatase levels compared to the GT rs 7041 and CC rs 4588 genotypes – 185.0 U/l (147.0–212.0) versus 259.5 U/l (207.0–334.5), p=0.021 and against 251.0 U/l (222.0–346.0), p=0.016. Area of practical application of research results: The results of the study can be used by working groups to make recommendations for the prevention and treatment of vitamin D deficiency and in the practice of health care facilities. Innovative technological product: association between allelic variants of the VDBP gene and vitamin D status in young children. Scope of application of innovative technological product: pediatrics, medical genetics. Conclusions. Genetic variants of VDBP may affect the absorption of vitamin D and cause variability in 25 (OH) D levels, which complicates the development of uniform recommendations for optimal prophylactic doses of vitamin D and necessitates additional research. The highest levels of 25 (OH) D were recorded in children with genotypes AA rs 4588 and TT rs 7041 of the VDBP gene, which showed high absorption when taking vitamin D supplements at a dose of 500 IU and even excessive concentrations of 25 (OH) D with long-term supplementation in higher dose

Enhancement of the Local CD8⁺ T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes

Longitudinal Analysis of Neuraminidase and Hemagglutinin Antibodies to Influenza A Viruses after Immunization with Seasonal Inactivated Influenza Vaccines

Neuraminidase (NA)-based immunity could reduce the harmful impact of novel antigenic variants of influenza viruses. The detection of neuraminidase-inhibiting (NI) antibodies in parallel with anti-hemagglutinin (HA) antibodies may enhance research on the immunogenicity and duration of antibody responses to influenza vaccines. To assess anti-NA antibodies after vaccination with seasonal inactivated influenza vaccines, we used the enzyme-linked lectin assay, and anti-HA antibodies were detected in the hemagglutination inhibition assay. The dynamics of the anti-NA antibody response differed depending on the virus subtype: antibodies to A/H3N2 virus neuraminidase increased later than antibodies to A/H1N1pdm09 subtype neuraminidase and persisted longer. In contrast to HA antibodies, the fold increase in antibody titers to NA after vaccination poorly depended on the preexisting level. At the same time, NA antibody levels after vaccination directly correlated with titers before vaccination. A difference was found in response to NA antigen between split and subunit-adjuvanted vaccines and in NA functional activity in the vaccine formulations

Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs

New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of M.tb within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent M.tb strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against M.tb when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent M.tb strain H37Rv