Репозиторий Университета

© 2018 American Society for Microbiology. The tick-borne pathogen Borrelia burgdorferi is responsible for approximately 300,000 Lyme disease (LD) cases per year in the United States. Recent increases in the number of LD cases, in addition to the spread of the tick vector and a lack of a vaccine, highlight an urgent need for designing and developing an efficacious LD vaccine. Identification of protective epitopes that could be used to develop a second-generation (subunit) vaccine is therefore imperative. Despite the antigenicity of several lipoproteins and integral outer membrane proteins (OMPs) on the B. burgdorferi surface, the spirochetes successfully evade antibodies primarily due to the VlsE-mediated antigenic variation. VlsE is thought to sterically block antibody access to protective epitopes of B. burgdorferi. However, it is highly unlikely that VlsE shields the entire surface epitome. Thus, identification of subdominant epitope targets that induce protection when they are made dominant is necessary to generate an efficacious vaccine. Toward the identification, we repeatedly immunized immunocompetent mice with live-attenuated VlsE-deleted B. burgdorferi and then challenged the animals with the VlsE-expressing (host-adapted) wild type. Passive immunization and Western blotting data suggested that the protection of 50% of repeatedly immunized animals against the highly immune-evasive B. burgdorferi was antibody mediated. Comparison of serum antibody repertoires identified in protected and nonprotected animals permitted the identification of several putative epitopes significantly associated with the protection. Most linear putative epitopes were conserved between the main pathogenic Borrelia genospecies and found within known subdominant regions of OMPs. Currently, we are performing immunization studies to test whether the identified protection-associated epitopes are protective for mice.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To specify the duration of persistence of antigens and DNA of Mycoplasma pneumoniae (M. pneumoniae) and Mycoplasma hominis (M. hominis) cells in the free state and as part of circulating immune complexes in blood of children suffering from bronchial asthma. Patients and methods. In the University Children’s Clinical Hospital of the Sechenov University, 161 children aged 1 to 14 years were observed. Group 1 (treatment group) included 126 children with bronchial asthma. 55 children (43.7%) had a mild course of disease, 52 children – moderate (42.1%) and 19 children (15.1%) – severe. All children were in the exacerbation period. Group 2 (control) consisted of 35 children with ARVI. The mean age of children in group 1 – 5.4 ± 1.8 years (79 boys (62.7%) and 47 girls (37.3%)); in group 2 – 5.7 ± 1.9 years (20 boys (57.1%) and 15 girls (42.9%). Diagnostic methods used: cultivation of mycoplasmas, preparation of immune serums, aggregate-haemagglutination assays (AHAA), polymerase chain reaction (PCR), direct immunofluorescence (DIF), methods of detection of circulating immune complexes (CIC). Results. AHAA examination of 126 serum samples of children from group 1 with BA, M. pneumoniae and M. hominis antigens in the free state were found in 73 and 50% of cases, respectively. In children of group 2 AHAA detected M. pneumoniae and M. hominis significantly more rarely: M. pneumoniae was found in 3 (8.6%) children (p = 95.3), M. hominis – in 2 (5.7%) children (p = 97.1). Further examination of serum samples of children with BA found M. pneumoniae and M. hominis cell DNA in 7.14 and 16.6% of cases, respectively. The work has shown that M. pneumoniae antigens are found in the composition of CIC in 55.5% of cases, M. hominis antigens – in 46.8% of cases, DNA – in 26.98 and 46.8%, respectively. For treatment of mycoplasma infection, children with BA received three azitromicin courses in the dose 10 mg/kg for 3 days with a 4-day interval. Conclusion. These data are indicative of long-term persistence of mycoplasma cell antigens and DNA in the free state and in CIC in blood of children with BA. Mycoplasmas can be regarded as one of the factors of inducing BA exacerbations in children. Tests for mycoplasma infection are indicated in patients with BA. Addition of macrolides to standard BA therapy in children with mycoplasma infection, as a rule, yields positive results.

© 2018 Media Sphera Publishing Group. All rights reserved. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults and is classified as either primary (idiopatic) or secondary MN according to underlying etiology (the later result from some known disease such as systemic autoimmune diseases, infections, malignancies, drugs, etc). In recent years, phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as two major podocytic antigens involved in the pathogenesis of idiopatic MN (IMN). And the discovery of circulating antibodies specific for these target antigens has transformed the diagnostic workup and significally improved management of IMN. However why do such antibodies develop is not conclusively established. The role of underlying genetic factors is discussed. The review presents the results of recent studies, that have shown significant associations of specific genetic factors (particularly human leucocyte antigen class II and PLA2R1 genes) with IMN.

© 2018 Russian Academy of Medical Sciences. All Rights Reserved. Cancer immunotherapy represents a promising and rapidly developing approach for the treatment of oncological diseases. Among the methods of personalized adjuvant immunotherapy, neoantigenic peptide-based drugs have demonstrated substantial efficiency. These drugs are designed to target mutant proteins arising from somatic alterations in the genome of tumor cells and thus stimulate immune response against tumor tissues. The methods of individual screening for potentially immunogenic mutations are mostly based on next-generation exome sequencing of tumor samples, which is a complex and costly procedure for clinical application. Targeted gene sequencing panels limited to a certain set of genes represent a reasonable alternative to WES. Targeted sequencing is also more efficient when there is a low amount of the sample DNA available. We have estimated the potential efficiency of targeted oncological panels in terms of somatic neoantigen profiling in colorectal cancer (colon and rectal adenocarcinoma). The clinical practice of identification of frequent somatic variants does not provide enough data for designing an efficient personalized drug when applied to low and medium mutated cancers such as colorectal cancer. Our analysis of 11 commercially available panels containing different number of genes has shown that neither the larger size of a panel nor its initial customization for colorectal cancer provides a significantly better estimation of an individual somatic mutation profile. The optimal approach is to use the general-purpose medium-sized cancer panels (2300-11200 amplicons and/or 150-600 genes). These panels allow to detect a sufficient number of immunogenic epitopes (>3) per patient for over 30-50% of patients.