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Vol 76, No 1 (2021)

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Immunogenicity and protectivity of the peptide vaccine against SARS-CoV-2
Ryzhikov A.B., Ryzhikov E.А., Bogryantseva M.P., Danilenko E.D., Imatdinov I.R., Nechaeva E.A., Pyankov O.V., Pyankova O.G., Susloparov I.M., Taranov O.S., Gudymo A.S., Danilchenko N.V., Sleptsova E.S., Bodnev S.A., Onkhonova G.S., Petrov V.N., Moiseeva A.A., Torzhkova P.Y., Pyankov S.A., Tregubchak T.V., Antonets D.V., Gavrilova E.V., Maksyutov R.A.

Background. In 2020, the pandemic caused by novel coronavirus infection has become one of the most critical global health challenges during the past century. The lack of a vaccine, as the most effective way to control the novel infection, has prompted the development of a large number of preventive products by the scientific community. We have developed a candidate vaccine (EpiVacCorona) against novel coronavirus infection caused by SARS-CoV-2 that is based on chemically synthesized peptides conjugated to a carrier protein and adsorbed on aluminum hydroxide and studied the specific activity of the developed vaccine.

Aims — study of the immunogenicity and protectivity of the peptide candidate vaccine EpiVacCorona.

Methods. The work was performed using standard molecular biological, virological and histological methods.

Results. It was demonstrated that EpiVacCorona, when administered twice, spaced 14 days apart, to hamsters, ferrets, and non-human primates (african green monkeys, rhesus macaques) at a dose of 260 μg, which is equal to one inoculation dose for humans, induces virus-specific antibodies in 100% of the animals. Experiments in hamsters showed this vaccine to be associated with the dose-dependent immunogenicity. The vaccine was shown to accelerate the elimination of the virus from the upper respiratory tract in ferrets and prevent the development of pneumonia in hamsters and non-human primates following a respiratory challenge with novel coronavirus.

Conclusions. The results of a preclinical specific activity study indicate that the use of EpiVacCorona has the potential for human vaccination.

Annals of the Russian academy of medical sciences. 2021;76(1):5-19
Management of the incidence of infectious diseases by applying preventive measures in the weakest period in its cyclicity
Savilov E.D.

Existing preventive measures have not been entirely efficient. Mainly they are aimed at solving social and economic issues, which demands both time and money. Considering this, it is necessary to find and sustain additional effective measures, based on patterns of development of infectious diseases, which could be more cost-effective. One of such approaches could be based on the theory of self-regulation of parasitic systems, which directs epidemiologists to conducting preventive measures before the rise of the number of cases to prevent increase in the agent’s virulence. Yet this theory does not provide the optimum time for preventive measures. Based on the main statements of the theory of self-regulation of parasitic systems and analysis of annual and/or long-term cyclicity, the article provides substantiation of the theory that the lowest level of incidence is the weakest period in its development. Epidemiological experiments, using bacterial dysentery as an example, showed that preventive administration of polyvalent dysenteric bacteriophage in risk groups (children going to preschool institutions) during two months of the lowest incidence level of the disease appeared to be effective. The positive effect took place in the stages of cyclic increase and decrease of long-term trends. The effect appeared in the groups of children and population in general with most marked decline in disease occurrence in its seasonal peak. The hypothesis that the lowest incidence level is directly related to seasonal climbs of the disease was proved by our earlier studies when we investigated influence of technogenic pollution of the environment on annual incidence rate of more than ten most common infectious diseases with different ways of transmission. Thus, the lowest incidence level of infectious diseases defines their future growth and/or decline, and, therefore, it can be used to conduct preventive measures.

Annals of the Russian academy of medical sciences. 2021;76(1):20-27
Pneumococcal infection in Russia: state of the issue
Briko N.I., Korshunov V.A., Lomonosov K.S.

Background: Pneumococcal disease is common cause of morbidity and mortality in adults and children worldwide. The severity of pneumococcal diseases determines their high socio-economic significance.

Aims: Estimate the burden of pneumococcal infection and vaccination coverage in Russia.

Methods: The data was obtained from federal surveillance system. The information obtained was analyzed using descriptive statistics methods.

Results: The annual incidence of community-acquired pneumonia in Russia was 491.7/100000 in 2011-2019. It ranges from 359.8/100000 among adults of working age to 1505.4/100000 among children 1-2 years old. The upward trend of incidence is observed throughout the period, most expressive among school-age children (7-17 years old). Total 29.2% of all pneumonia have an identified etiology. 94% of pneumonia with known etiology are bacterial, 8.4% among it are pneumococcal.

Pneumonia accounts for 57% of all deaths from respiratory diseases among children under five (3.7/100000) and 34% among elderly. The death rate from pneumonia in 2009-2018 tends to decrease. In 2018, 25.5 thousand deaths from pneumonia were registered (17.5/100000). The highest  rate is observed among children under one year (14.0 /100000) and elderly (41.2 /100000).

There is a downward trend in incidence of otitis media. The incidence in children under 14 was 2612.6/100 000 in 2018. The incidence of bacterial meningitis is 1.4/100 000. Every year 2-3 thousand cases are registered, 43-52% of which are among children (3.04/100000., maximally in children under one year old, 13.2/100000).

The level of vaccination against pneumococcal infection is increasing annually, but the proportion of children who have received a completed course of vaccination remains insufficient (64.6% in 2019). Coverage among the adult population was 2.3% (3.8% among those over 60). The main contingents of vaccinated adults are conscripts (coverage 67.4%) and people with chronic lung diseases (coverage 15.1%).

Conclusions: The socio-economic and epidemiological burden of diseases associated with pneumococcal infection in Russia remains high. Accurate assessment of morbidity and mortality rates caused by St. pneumoniae diseases isnt possible due to the insufficient level of their ethological identification. Further efforts are required to achieve high level of herd immunity against pneumococcal infection through vaccine prevention during COVID-19 pandemic.

Annals of the Russian academy of medical sciences. 2021;76(1):28-42
Conceptual approaches to finding effective treatment for a new coronavirus infection at different stages
Kamalov A.A., Mareev V.Y., Orlova I.A.

The article attempts to analyze the change in philosophy in approaches to the treatment of COVID-19 that have occurred in recent months, based on published research and their own experience in the treatment of a new coronavirus infection at the medical research and education center of Moscow state University.  Emphasis is placed on the rationale for the phased use of different types of therapy. The reasons for using spironolactone in patients with COVID-19 as a drug for etiotropic and pathogenetic therapy are discussed in detail. The authors conclude that the use of antiviral drugs in combination with drugs that prevent the entry of the SARS-CoV-2 virus into cells from the first days of the disease should be supplemented with pre-emptive anti-inflammatory therapy that interrupts the progression of the disease. The parallel use of anticoagulants that reduce the risk of thrombotic and thromboembolic complications.

Annals of the Russian academy of medical sciences. 2021;76(1):43-50
COVID-19-associated secondary hemophagocytic lymphohistiocytosis (cytokine storm syndrome)
Alekseeva E.I., Tepaev R.F., Shilkrot I.Y., Dvoryakovskaya T.M., Surkov A.G., Kriulin I.A.

In most cases, COVID-19 has a favorable outcome. However, the risk of developing critical forms of the disease, including secondary hemophagocytic lymphohistiocytosis – HLH (cytokine storm syndrome), remains high. This dictates the interest in studying pathogenetic mechanisms, features of the clinical picture, laboratory and instrumental criteria for covid-19 disease. The article analyzes the causes of acute respiratory distress syndrome and multiple organ failure as manifestations of HLH. The necessity of monitoring signs of hyperinflammation (ferritin, C-reactive protein, etc., biomarkers of inflammation) and activation of thrombosis is substantiated, in order to make timely decisions about the beginning of pathogenetic therapy. However, there are limitations for routine testing of the level of Pro-inflammatory cytokines. Information about the diagnostic criteria of HLH is summarized, and the expediency of these criteria for establishing secondary HLH, which has complicated the course of COVID-19, is emphasized.

Annals of the Russian academy of medical sciences. 2021;76(1):51-66
Genetic aspects of Ebstein anomaly and related heart diseases
Penyaeva E.V.

Ebstein anomaly is a congenital heart disease, which is characterized by the presence of atrialized portion of the right ventricle, formed as a result of displacement of the tricuspid valve leaflets into the right ventricle and their partial adherence to the underlying myocardium. Atrialized portion in the right ventricle occupies the space between the fibrous annulus of the right atrioventricular orifice and the functional annulus of tricuspid valve, which represents a zone of closure of free (non-adherent to the underlying myocardium) edges of its leaflets. Ebstein anomaly is very rarely isolated, and can be combined with a number of heart diseases and be an integral part of hereditary syndromes. Currently, the role of genetic research in the investigation of the etiology of human diseases as well as understanding of the relationship between different diseases is increasing. The review presents literature data on the combination of Ebstein anomaly with other heart diseases (congenital heart diseases, Wolf-Parkinson-White syndrome, cardiomyopathies, including left ventricular noncompaction), inter alia, within the scope of hereditary syndromes (Noonan syndrome, 8p deletion syndrome, 18q deletion syndrome, 1p36 deletion syndrome, Pierre Robin syndrome). Genetic factors (gene and chromosomal mutations) lying at the core of Ebstein anomaly, as well as heart diseases combined with it, are highlighted. The analysis of published data suggests that Ebstein anomaly is a monogenic disease, and is characterized by allelic and locus genetic heterogeneity. The combination of Ebstein anomaly with other heart diseases is based on their genetic linkage.

Annals of the Russian academy of medical sciences. 2021;76(1):67-74
Extracellular neutrophil traps (NETs) in the pathogenesis of thrombosis and thromboinflammation
Bitsadze V.O., Slukhanchuk E.V., Khizroeva J.H., Tretyakova M.V., Shkoda A.S., Radetskaya L.S., Makatsariya A.D., Elalamy I., Gris J., Grandone E.

This article summarizes numerous studies on the relationship of biological processes such as inflammation and thrombosis. The huge role of neutrophils and the extracellular neutrophil traps (NETs) secreted by them has been demonstrated. The discovery of NETs has opened new horizons in the understanding of neutrophil biology and the role of these cells in the body. The use of chromatin in combination with the intracellular proteins, as an effective antimicrobial agent has ancient roots and changes our understanding of chromatin only as a carrier of genetic information. Through NETs, neutrophils can contribute to the development of pathological venous and arterial thrombosis or “immunothrombosis”, as well as atherosclerosis. NETs release has been shown to be one of the causes of thrombosis in conditions such as sepsis and cancer. The presence of NETs in these diseases and conditions makes it possible to use them or individual components as potential biomarkers. NETs and their components may be attractive as therapeutic targets. Further studies of neutrophils and NETs are needed to develop new approaches to the diagnosis and treatment of inflammatory and thrombotic conditions. Perhaps long-forgotten drugs will find a new area for effective use.

Annals of the Russian academy of medical sciences. 2021;76(1):75-85
Human embryo genome editing: an interdisciplinary approach
Grebenshchikova E.G., Andreyuk D.S., Volchkov P.Y., Vorontsova M.V., Ginter E.K., Izhevskaya V.L., Lagunin A.A., Polyakov A.V., Popova O.V., Smirnikhina S.A., Tishchenko P.D., Trofimov D.Y., Kutsev S.I.

The prospects for the human embryos genome editing cause intense debates both in the scientific community and in general public. While the main attention of scientists is focused on the safety, effectiveness and clinical feasibility of the inherited genome editing, the public pays attention to the bioethical aspects of the issue - the prospects of a “baby design”, the development of new forms of social inequality and intervention in human evolution. The authors conducted an interdisciplinary analysis of medical genetics and bioethical issues of human embryo genome editing, revealed the possibilities and limitations of genome editing technology, and considered the specifics of ethical discussions. The conceptualization of the main approaches of natural and social sciences in a general theoretical framework made it possible not only to take into account the complex nature of the issues, but also to create the prerequisites for its further productive discussion.

Annals of the Russian academy of medical sciences. 2021;76(1):86-92
Interagency in health care children and adolescents: WHO recommendations and Russian realities
Schepin V.O., Chicherin L.P., Popov V.I., Esaulenko I.E.

The article presents the materials of systematization and scientific study of the main international and Russian normative documents in the field of healthcare and rights of children and adolescents aged 0-17, and of the practical implementation of an intersectoral/interdepartmental approach in relevant programs. A set of modern methods of socio-hygienic and medical-organizational research, including statistical, historical insights, expert evaluation, study of departments’ experience, and others was applied, with an emphasis on analysis.

Based on the model of the younger generation, the authors consider the current problems of implementing an interdepartmental approach to healthcare and protection of the rights of children and adolescents, recommended in recent years by leading international organizations, primarily The United Nations (UN): and the World Health Organization (WHO). The authors analyze the leading Russian normative documents based on international policy and illustrates the state of the approach in the Russian Federation, which is considered to be the leading, most effective mechanism for achieving the goals of strategies and integrated programs in this area, with an emphasis on preventive measures and the organization of primary healthcare as the most accessible and affordable to the public.

The results of a comprehensive analysis of federal and international official documents actualized the need for intersectoral activities in healthcare, education, social protection and other systems to strengthen the health promotion of the younger generation, which is considered to be the less protected group of population from the perspective of health and social well-being. The article shows the importance of further improvement of comprehensive research on the scientific justification of optimal, real and effective for the federal and territorial levels of organizational methods for interdepartmental healthcare of the younger generation in Russia.

Annals of the Russian academy of medical sciences. 2021;76(1):93-102
Vitamin D-binding protein: multifunctional component of blood serum
Povaliaeva A.A., Pigarova E.A., Romanova A.A., Dzeranova L.K., Zhukov A.Y., Rozhinskaya L.Y.

Vitamin D-binding protein (DBP) was discovered more than half a century ago as a polymorphic serum protein and is currently characterized by a variety of physiological properties. First of all, DBP carries the bulk of vitamin D metabolites circulating in the bloodstream, while albumin is the second most important transport protein, especially in patients with a low concentration of DBP in serum. Since it was discovered that only 1–2% of the total circulating DBP have occupied steroid binding sites, a vigorous study of other potential biological roles of DBP was initiated: actin utilization, regulation of inflammation and innate immunity mechanisms, fatty acid binding, effects on bone metabolism and participation in the tumor pathogenesis. This review focuses on the main known biological functions of DBP.

Annals of the Russian academy of medical sciences. 2021;76(1):103-110
A retrospective study of the clinical and laboratory predictors and morphological characteristics of the parathyroid carcinoma
Krupinova J.A., Voronkova I.A., Ajnetdinova A.R., Abrosimov A.Y., Kryukova I.V., Lukyanov S.V., Veretennikova J.S., Tevosyan L.K., Melnichenko G.A., Mokrysheva N.G.

Background: there are no specific markers of the parathyroid carcinoma (PC) therefore, the development of algorithms for identifying high-risk patients is an urgent task.

Aims: to determine the clinical and laboratory predictors of PC and to identify the factors of a poor prognosis.

Materials and methods: A multicenter retrospective study included 242 patients with primary hyperparathyroidism (PHPT) who were divided into groups: 162 with adenomas, 30 with аtypical adenomas (АА) and 50 patients with PC. Data collection and analysis was carried out from 2017 to 2020. The primary goal— assessment of the possibility of PС using preoperative laboratory and instrumental data. The group of PC was divided into subgroups: the patients in recurrences (n=17) and remission (n=33). The level of the total calcium, albumin, alkaline phosphatase (ALP), ionized calcium (Ca ++) in the blood were determined on the automatic biochemical analyzer; the level of parathyroid hormone (PTH) by electrochemoluminescent analyzer. The size of the PG determined by the ellipse formula: V (cm3) = (A × B × C) × 0.49. Statistical analysis was performed with Statistica 13 and SPSS software packages. For multiple comparisons, the Bonferroni correction was applied.

Results: the group of patients with increased risk of PC include persons with increased level of PTH >443 pg/ml, Ca++ >1.5 mmol/l, total calcium >3.2 mmol/l, ALP >176 IU/L, V of tumors >2.6 cm3, largest size >22.5 mm (p <0,001). Heterogeneous structure is more typical to PC compared to the АА (p = 0,004 and р = 0,011), the same applies to indefinite contour (р = 0,001 и р = 0,011). Pathological mitosis is a prognostically unfavorable factor of recurrence of PC (р=0,007).

Conclusions: the patients with PC and AA are characterized with more aggressive course of PHPT compared to the group of adenomas.

Annals of the Russian academy of medical sciences. 2021;76(1):111-124
Anniversary of RAS Academician Ivan Ivanovich Dedov
Starodubov V.I.

The Hero of Labor of the Russian Federation Ivan Ivanovich Dedov turned 80 on February 12! The Department of Medical Sciences of the Russian Academy of Sciences congratulates RAS Academician Ivan Ivanovich Dedov!

Annals of the Russian academy of medical sciences. 2021;76(1):125-127
Congratulations on the anniversary of Alexey Vasilyevich Shabunin!

The staff of the journal "Annals of the Russian Academy of Medical Sciences" congratulates on the 60th anniversary of the corresponding member of the RAS, chief physician of the S.P. Botkin City Clinical Hospital , Chief Surgeon of the Moscow Healthcare Department, Honored Doctor of the Russian Federation, Professor Alexei Vasilyevich Shabunin.

Annals of the Russian academy of medical sciences. 2021;76(1):128-128

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