Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Nozdracheva AV, Gritsik AA, Kuzin SN, Semenenko TA

As the modern society becomes more vaccine-dependent, the need arises for population immunity studies aimed to estimate the prevalence of antibodies against a particular infection in the donors from different populations, including sentinel groups. This work reveals the actual susceptibility of the Russian population to a number of vaccine preventable infections, including measles, rubella, and mumps. The study was conducted using blood serum samples provided by the Blood serum bank of Gamaleya Federal Research Center for Epidemiology and Microbiology (Moscow). Of 866 samples used in the study, 293 and 117 samples had been collected from healthcare workers in 2011 and 2017, respectively; 220 samples had been obtained from military servants in 2016–2017, and 236 samples had been collected from healthy donors in 2016. All samples were studied by solid phase enzyme immunoassay using diagnostic kits by Vector-Best (Russia). We discovered that 19.4 % and 28.8 % of individuals were susceptible to measles and mumps, respectively, which is insufficient for ensuring epidemiological safety (the herd immunity thresholds for these diseases are 7 % and 15 %, respectively) and puts the population at risk of infection spread, should the pathogens enter the country. The proportion of individuals susceptible to rubella was 6.5 %, which is below the herd immunity threshold (7 %).

Received: 2017-09-22

Published online: 2018-01-14

DOI: 10.24075/brsmu.2017-05-05

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VIEWS 5103

Mazunina EP, Kleymenov DA, Manuilov VA, Gushchin VA, Tkachuk AP

Multiplex screening assays for measuring antibodies to vaccine-preventable infections are routinely used in large-scale seroepidemiological studies, but not commercially available, because such studies are too specific and normally employ a particular type of the assay only once. This prompts researchers to develop their own solutions for exploring herd immunity. In this work we discuss theoretical principles and practical approaches to developing multiplex screening assays and give examples of protocols and recommendations based on our own experience in the field.

Received: 2017-09-26

Published online: 2018-01-13

DOI: 10.24075/brsmu.2017-05-04

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VIEWS 6187

Cell-mediated immunity and the cytokine interferon gamma (IFNγ) have an important role in promoting host resistance against tuberculosis-causing mycobacteria (TBM), but the exact mechanism of developing immunity against tuberculosis (TB) is unknown. In this work we evaluate the immune response in TB and the association between IFNG gene polymorphism rs2069705 (T-1488C) and the intensity of specific immune reactions in children. The study was conducted in 310 children below 18 years distributed into 3 groups: the TB group included 110 children with TB confirmed by medical evaluation; the LTB group consisted of 156 children with latent infection; and the NTB group was represented by 44 non-infected children. A few immunoassays and molecular-genetic tests were performed; specifically, we evaluated the immune status of patients and the distribution of genotypic frequencies of the studied polymorphism, in the context of previous vaccination against TB. The cell-mediated immune response was mild in children with LTB, while in children with TB inflammation showed signs of chronicity due to the lack of functional activity of immune cells (p < 0.05). We also measured IFN-γ synthesis induced by specific mitogens (PPD-L, CFP32B, Rv2660c, ESAT6, 85a and ESAT6-CFP10), only to detect attenuation of the immune response in patients with TB, which was associated with the heterozygous rs2069705 variant (p < 0.05). Children with homozygous TT and CC genotypes demonstrated a more pronounced immune response. Low effectiveness of the TB vaccine was shown to be associated with the heterozygous genotype (50 %), while its high effectiveness was associated with the homozygous T genotype (40 %), possibly indicating the protective role of the latter. Our findings suggest that the studied polymorphism (specifically, its heterozygous variant) can be a predictive marker of TB in children.

Received: 2017-09-24

Published online: 2018-01-13

DOI: 10.24075/brsmu.2017-05-03

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VIEWS 5042

Kleymenov DA, Mazunina EP, Lunin VG, Koptev EYu, Manuilov VA, Gushchin VA, Tkachuk AP

So far BCG, a live attenuated Mycobacterium bovis strain remains the only available vaccine for tuberculosis prevention and control. Although BCG is effective against miliary tuberculosis and tuberculous meningitis in children, it barely protects adults and adolescents from the pulmonary form of the disease or reactivation of the latent infection. Still, its effectiveness can be increased by using recombinant booster vaccines containing both M. bovis and M. tuberculosis antigens. This article reports preliminary data on the safety and immunogenicity of a recombinant vaccine candidate, GamTBvac, developed for tuberculosis prevention. Its immunogenicity was studied in 12 volunteers. Over the course of 20 weeks following GamTBvac administration, we measured cell-mediated and humoral immune responses using interferon-gamma release assays and multiplex xMAP- based immunoassays. On day 140 after the first administration of the vaccine, 10 participants of the study (83 %) still showed a positive cellular response to all antigens contained in the vaccine. Both sense antigens CFP10 and ESAT6 induced production of IgG antibodies between days 98 and 140 of the observation. The Ag85 antigen induced a relatively weak humoral response. On the whole, the recombinant GamTBvac is safe and activates cell-mediated and humoral components of the adaptive immunity, forming immunological memory.

Received: 2017-09-20

Published online: 2018-01-13

DOI: 10.24075/brsmu.2017-05-02

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VIEWS 5288

Gushchin VA, Manuilov VA, Mazunina EP, Kleymenov DA, Semenenko TA, Gintsburg AL, Tkachuk AP

Immunological memory is one of the key features of the adaptive immunity. It confers the ability to resist infection and prevents development of cancer or autoimmune diseases. Most importantly, immunological memory mediated by preexisting antigen- specific clones of T- and B-cells ensures a rapid and effective response to an invasion by a previously encountered pathogen. Since vaccination induces a specific long-lived response to infectious agents, it becomes a basis for preventive medicine. In a human population, immunological memory of individuals shapes the so-called herd or community immunity crucial for national health. The present review touches upon significant population-wide research studies of immunological memory with regard to immunization. We discuss the principles of serological testing and the outcomes of serological monitoring conducted in different countries, and talk about standard and innovative analytical approaches to studying immunological memory. We also pinpoint the drawbacks of methods used for herd immunity assessment in Russia and propose a comprehensive system for seroepidemiological surveillance.

Received: 2017-09-24

Published online: 2017-12-11

DOI: 10.24075/brsmu.2017-05-01

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VIEWS 5831

Vorobyeva ES, Lipengolts AA, Cherepanov AA, Grigorieva EYu, Nechkina IN, Kalygina NS, Sokovikov AV, Kulakov VN, Sheino IN

Contrast-enhanced radiotherapy (CERT) is a type of radiation therapy used to enhance the radiation dose absorbed by the tumor while sparing surrounding healthy tissues. The present study aims to assess feasibility of using 6 MV photons to increase radiation absorption in CERT. The dose absorbed by iodinated water was directly measured by ferrosulphate dosimetry. Concentrations of iodine (a dose-enhancing agent) ranged from 2.5 to 50 mg/ml. Solutions were exposed to 5 Gy radiation generated by the clinical linear accelerator SL75-5MT (Russia). The radiation dose applied did not account for increased absorbance due to the presence of iodine atoms. No reliable increase in the absorbed dose was observed for iodine concentrations ranging from 2.5 to 20 mg/ml. For 50 mg/ml concentrations the absorbed dose increased by 13% ± 5 % (p < 0.05). Normally, dose-enhancing concentrations observed in CERT studies range from 2.5 to 15 mg/ml, therefore, as demonstrated by our findings, employing 6 MV photon energy spectra in order to reach a therapeutically significant effect is unreasonable.

Received: 2017-08-25

Published online: 2017-10-31

DOI: 10.24075/brsmu.2017-04-10

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VIEWS 4748

Gordukova MA, Divilina YuV, Mishukova OV, Galeeva EV, Prodeus AP, Filipenko ML

In this article we present a clinical case of brain abscess in a girl aged 14 years and 11 months caused by a pathogen that could not be identified by routine microbiological testing. Before admission and during her stay in the hospital, the teenager did not have fever. Diagnosis and treatment were impeded by allergic responses to a wide range of antibiotics. The patient underwent three surgical interventions. Pus culture was performed 4 times, showing no growth. A PCR assay was run twice, but both times the results came out negative. Therefore, a decision was made to amplify and Sanger-sequence the 16S rRNA gene from the DNA extracted from patient’s pus. BLAST showed a 99 % homology of the obtained nucleotide sequence to the sequence of the 16S rRNA gene of Streptococcus intermedius (strain ChDC B589, KF733728.1) which had been previously shown to play a role in brain abscess development. Treatment ex juvantibus against the pathogen was started before sequencing results were available. The patient responded positively, the symptoms were alleviated and the condition improved. Thus, we conclude that in some cases sequencing may be the only diagnostic technique capable of identifying the pathogen.

Received: 2017-07-04

Published online: 2017-10-31

DOI: 10.24075/brsmu.2017-04-09

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VIEWS 4720

Kolomeichuk SN, Alekseev RV, Putilov AA, Meigal AYu

This work aims to study distribution of allele frequencies of the ACE and BDKRB2 genes coding for the angiotensin-converting enzyme and the bradykinin receptor β2, respectively, in athletes specializing in different sports and to establish the associations between the studied genotypes and heart rate variability. The study included 75 male athletes. Polymorphisms of ACE and BDKRB2 (I/D and +9/−9, respectively) were studied by PCR. A significant difference was revealed in the −9/−9 genotype frequency between the studied groups of athletes. Parasympathetic nerve activity prevailed in the athletes with the I allele of the ACE gene. Time-domain parameters of heart rate variability had low values in the carriers of the D/D genotype. In the athletes with the ACE I/I genotype the time-domain parameters differed from those typical for the I/D and D/D genotype carriers. Participants homozygous for −9 BDKRB2 had the lowest heart rate in the studied sample, implying an increased contribution of parasympathetic activity to heart rate regulation. The −9 allele of BDKRB2 was found to be associated with the minimal R — R interval between consecutive hear beats. We conclude that polymorphisms I/D of ACE and +9/−9 of BDKRB2 can indicate individual patterns of heart rate regulation in athletes from the Republic of Karelia.

Received: 2017-08-25

Published online: 2017-10-30

DOI: 10.24075/brsmu.2017-04-08

Comments 0

VIEWS 4948