Vol 14, No 4 (2024)

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Full Issue

REVIEWS

The principle of ecological and molecular consensus in reconstructed plague microbe Yersinia pestis phylogeny

Suntsov V.V.

Abstract

In the second half of the 20th century, through the efforts of scientists from many countries, a coherent theory of natural plague foci (sylvatic plague) was formulated, attempted to describe the history of the origin and evolution of the causative agent of plague infection, the microbe Yersinia pestis. But the accumulated knowledge in this regard remained extremely limited. Envisioned by the modern phylogenetics, the methods of phylogenetic constructions in the pregenomic time were rather primitive, “manual”, characteristic of early empirico-intuitive Haeckel phylogenetics. Since the beginning of the 21st century, the introduction of genomic methodologies in the study of the plague pathogen allowed to detail the intraspecific diversity (subspecies, genovariants) of this particularly dangerous pathogen at the level of geographical and local populations (individual natural foci) around the world and to bring the diagnostics and description of intraspecific diversity to a high degree of perfection. Two important discoveries were made. First, the direct ancestor of the plague microbe was reliably established, it turned out to be the causative agent of intestinal infection — Far Eastern scarlet-like fever (Y. pseudotuberculosis 0:1b). Secondly, the evolutionary youth of the plague pathogen was shown, the “molecular clock” showed the time of its divergence from the ancestral population no earlier than 30 thousand years ago. Thus, the root of the phylogenetic tree of Y. pestis was fully characterized. Nevertheless, molecular genetic (MG) achievements do not yet allow to reveal the secrets of its phylogeny, i.e. the origin and sequence of world expansion. The most important reason is the high dependence of the MG of phylogeny reconstructions on the choice of evolutionary model for the analyzed characters: the model of neutral evolution is traditionally accepted, but its adequacy in relation to Y. pestis phylogeny is questioned by many well-known ecological (in the broad sense) facts. At the same time, MG achievements contributed to the creation of an ecological (ECO) approach based on the provisions of the theory of natural plague foci in an updated version, according to which the plague pathogen is an evolutionarily young pathogen descended from a psychrophilic pseudotuberculous ancestor. The presumptive ECO scenario has no obvious natural-scientific and historical contradictions and can serve as a null hypothesis for improving the MG methodology of phylogenetic constructions for plague and other similar microbes. It is suggested that the creation of a real phylogeny of the plague microbe is possible only based on integration of MG and ECO approaches.

Russian Journal of Infection and Immunity. 2024;14(4):645-654
pages 645-654 views

Prospectives of developing therapeutic HPV vaccines

Raevskaya N.M., Nikitina T.N., Simbirtsev A.S., Solovyeva I.L., Volgin A.R., Korovkin A.S.

Abstract

Human papillomavirus (HPV) represents one of the most serious global public health problems. Malignant female and male diseases mainly result from persistent HPV infection. Cancer belongs to a high mortality rate disease. It has been established that HPV infection causes about 70% vaginal cancer, 50% male genital cancer, 90% anal cancer and 60% head-and-neck cancer. Annually, a large number of people develop various HPV-caused cancer types, dominated by cervical cancer, one of the most common and aggressive types of cancer that threatens health holding the fourth place among most female common cancer worldwide. According to the World Health Organization (WHO), in 2020, about 600 cases of cervical cancer are recorded daily in different countries. Emergence of cervical cancer is closely related to factors such as long-term (persistent) HPV infection and somatic mutations of the host genome. Although HPV infection can be detected and cured early with highly effective screening methods and surgical procedures, the carcinogenic risk of HPV related diseases constantly increases, which elimination faces certain difficulties, especially in low- and mid-developed countries. The most acceptable solution to this is development and implementation of therapeutic vaccines for prevention and treatment of HPV related diseases. Three licensed HPV vaccines based on L1 type virus-like particles (L1-VLPs) technology are available globally: bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent (HPV-9) vaccines. These vaccines demonstrated effectiveness in reducing HPV-related cervical cancer rate by up to 90% worldwide. However, the therapeutic effect of these vaccines on persistent HPV infection and lesions has not been observed. Therapeutic HPV vaccines candidates targeted Ye6/Ye7 cancer proteins activate cellular immunity that eliminates existing HPV infection. Here we review types, mechanisms of action and clinical effects of therapeutic HPV vaccines, as well as current and future developments in the field for prevention and treatment of HPV related diseases.

Russian Journal of Infection and Immunity. 2024;14(4):655-671
pages 655-671 views

New promising antiseptics for individual antiviral protection against seasonal infections including COVID-19

Lepekhova S.A., Grigor’ev G.E., Kurganskiy I.S.

Abstract

Seasonal viral infections of the upper respiratory tract are widespread throughout the world. The SARS-CoV-2 pandemic has revealed the importance of timely personalized prevention of acute viral diseases and related bacterial complications. One of the main directions in the preventing viral infections relies on the development of effective antiseptics to inactivate viruses on the hands and mucous membranes. To effectively destroy SARS-CoV-2, the WHO recommends two antiseptics: a 70% ethanol solution and sodium hypochlorite. The proposed antiseptics are outdated and have an irritating effect on the skin and mucous membranes. In connection with this, a promising research direction includes development of new antiseptics with selective toxicity, low volatility, low coefficients in the oil-water system, weak lipophilic properties, low absorption into the vacuolar skin structures and low content of toxic impurities. One of these antiseptics is anavidin. The development and selection of molecules has been carried out, the next planned stage will be assessment of the effectiveness and safety of new molecules, including preclinical and early phase clinical trials, also analyzing prevention of viral infections, e.g. COVID-19.

Russian Journal of Infection and Immunity. 2024;14(4):672-680
pages 672-680 views

ORIGINAL ARTICLES

Genetic profile of carbapenem-resistant Acinetobacter baumannii strains

Alekseeva A.E., Brusnigina N.F., Makhova M.A.

Abstract

The purpose of the research: the molecular genetic characteristic of A. baumannii carbapenem-resistant strains, including clonal affiliation, resistome and virulome pattern analysis, description of genetic environment resistance determinants, comparative genetic analysis, and assessment of phylogenetic relationships are presented in the work. The studied A. baumannii strains belonged to sequence types ST2Pas/ST2062.2063Oxf (n = 5) and ST78Pas/ST1757Oxf (n = 2). The nucleotide sequences of the studied A. baumannii ST2Pas/ST2062.2063Oxf strains were grouped into a single cluster according to phylogenetic analysis. And the sequences of the A. baumannii ST78Pas/ST1757Oxf strains were combined with the nucleotide sequence of the A. baumannii AbCTX5 strain, isolated in France in 2015. The presence of intrinsic (OXA-51-like) and acquired carbapenemases genes was shown in A. baumannii strains. In particular, blaOXA-23 are identified in members of ST2Pas/ST2062.2063Oxf, and in A. baumannii ST78Pas/ST1757Oxf strains — blaOXA-72 as part of the plasmid DNA. The A. baumannii ST78Pas strains possessed additional extended-spectrum beta-lactamase genes. Тhe CTX-M-115 cephalosporinase gene are present in both strains, and the A. baumannii strain NNAb_2023.3 has the blaCARB-16 gene. Most A. baumannii strains are characterized by the presence of acquired genes for enzymatic modification of macrolides (mph(E), msr(E)), chloramphenicols (catB8), aminoglycosides (aadA, aph(3'')-Ib, aph(6)-Id, aac(6')-Ib, aph(3')-Ia, armA). A comparative analysis showed that in A. baumannii ST2Pas/ST2062.2063Oxf strains the resistance determinants to macrolides and aminoglycosides are located in the Tn6279-like transposon, and the aminoglycosidases genes aph(3'')-Ib, aph(6)-Id are associated with the IS91-like mobile element. In A. baumannii ST78Pas/ST1757Oxf strains, resistance genes to aminoglycosides, macrolides, sulfonamides, and beta-lactamase genes are grouped in a region from 60 to 80 Kb long between the glmS and hutC genes. The presence of mutations in the gyrA and parC genes associated with resistance to fluoroquinolones were characterized in all A. baumannii strains. Thus, new knowledge about the genetic profile of carbapenem-resistant A. baumannii strains representing epidemically significant international clonal lineage has been obtained.

Russian Journal of Infection and Immunity. 2024;14(4):681-689
pages 681-689 views

Evaluating peripheral blood lymphocyte subset composition and lipopolysaccharide-induced cytokine secretory activity in mononuclear leukocyte cultures from patients with febrile and meningeal forms of tick-borne encephalitis

Ilyinskikh E.N., Voronkova O.V., Reshetova A.V., Hasanova R.R., Esimova I.E., Chernyshov N.A., Yampolskaya O.V., Yampolskaya A.V., Polomoshnova E.M., Minakova E.V.

Abstract

Introduction. Multiple studies on immune response in patients with various clinical forms of tick-borne encephalitis (TBE) have shown conflicting results. The study aim was to estimate the changes in peripheral blood lymphocyte subset counts and activity of spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production in the mononuclear leukocyte cultures in patients with febrile and meningeal acute TBE. Materials and methods. Groups 1 and 2 included 16 and 12 patients with febrile and meningeal acute TBE, respectively. The control group included 13 healthy donors. Hemogram and T-lymphocyte, T-helper cell, T-cytotoxic and NK cell counts were analyzed by flow cytometry at week 1 of the disease as well as the spontaneous and LPS-stimulated secretion levels of TNFα, IL-1β, IL-6, IL-10, IL-8, and MCP-1 were assessed by ELISA in the supernatants of mononuclear cell cultures twice: during hospitalization and two weeks later. Statistical analysis was performed by the Mann–Whitney U-test, and Wilcoxon test. Results. Group 2 demonstrated significant decrease in spontaneous and/or LPS-stimulated levels of proinflammatory cytokines IL-1β, IL-6, MCP-1, and TNFα, but showed higher IL-8 level as compared with Group 1. In addition, spontaneous and/or LPS-induced levels of IL-6 and TNFα in Group 2 did not significantly differ from the controls, which presumably also indicated the suppression of their production. In contrast, spontaneous and/or LPS-induced levels of IL-1β, IL-6, MCP-1, and TNFα in Group 1 were higher than in the controls. The spontaneous IL-10 level in the patients from both groups were higher than in the controls. Peripheral blood lymphocyte and T-cytotoxic T-lymphocyte counts in both groups of TBE patients were lower than in the controls. There was significant increase in neutrophil counts, decrease in NK cell count in Group 2 as compared to the patients with a milder febrile form. Conclusion. Meningeal acute TBE patients was presumably associated with inadequate immune response with NK cell deficiency, T-cell dysfunction, increased neutrophil count in the peripheral blood and impaired pro-inflammatory cytokine production related to innate immune response.

Russian Journal of Infection and Immunity. 2024;14(4):690-700
pages 690-700 views

Assessed correlation between biological diversity of oropharyngeal microbiota and atopic dermatitis severity and exacerbations

Pobezhimova O.O., Zhestkov A.V., Lyamin A.V., Reshetnikova V.P., Ereshchenko A.A., Alekseev D.V.

Abstract

Atopic dermatitis (AtD) is a multifactorial inflammatory skin disease characterized by itching, chronic recurrent course and age-related features of lesions. AtD pathogenesis has not been fully elucidated yet. An important factor for AtD emergence and progression is the imbalance in symbiotic microbiota. The research publications provide a few studies about a role for oropharyngeal microorganisms in AtD immunopathogenesis. The aim of the study is to analyze biological diversity of oropharyngeal microbial communities in varying AtD severity. 97 male patients, aged from 16 to 19 years, with different AtD severity were included in the study. Culture study of oropharyngeal discharge was also performed. Biological material was seeded on the expanded list of growth media and incubated for 5 days at the 37°С. To assess the biological diversity of the oropharyngeal microbiota, the coefficient of constancy (C) was used, in order to classify individual microorganisms as permanent, additional or transient. Statistical data processing was performed using the Stat Tech software (version 4.0.0, Stattech LLC, Russia). While examining biological diversity of the oropharyngeal microbiota in AtD patients, 58 microbial species were isolated and identified. After statistical analysis the significant differences in frequency of isolation, depending on different AtD severity were observed for microbes such as Streptococcus vestibularis and Rothia dentocariosa. When R. dentocariosa is isolated from the oropharynx, the chances of AtD exacerbation emergence decreased by 6 times, whereas in case of S. vestibularis, on the contrary, it increased by 5 times. Therefore, identification of transitions of individual microbes from transient to additional and permanent microbiota and vice versa, depending on the AtD stage and severity, allows to analyze an influence of specific microorganisms in AtD pathological processes and to establish definite new microbiological predictors of AtD exacerbation and remission.

Russian Journal of Infection and Immunity. 2024;14(4):701-708
pages 701-708 views

Features of influenza virus hemagglutinin genes and their recoding possibilities

Kharchenko E.P.

Abstract

The world has already entered the stage of increasing odds for a new pandemic, which prompts to seek out for new flu vaccines, because existing vaccines demonstrate only suboptimal effectiveness. With the Covid-19 pandemic, the possibility of using mRNA vaccines has been opened up, and a prospect of finding hemagglutinin (HA) gene mRNA-based new influenza vaccines seems very attractive. As a rule, the mRNA vaccine is a product of recoding, which ensures the mRNA stability. However, the results of mRNA recoding can be ambiguous. The purpose of this report is to analyze the features of genes and proteins and to consider opportunities and limitations in their recoding. Primary structures of NA proteins and relevant genes were retrieved from Internet publicly available databases. The amino acid composition and frequency of dipeptides, nucleotide and dinucleotide compositions, %GC, translational code and compositions of neighboring di- and tricodones, distribution along primary structure for explicit and synonymous mutations were determined. H1N1 and H3N2 subtypes have both specific and general features (limitations) in their genes, differing not only in the number of protein substitutions, but also in the number and distribution of gene synonymous codons, which do not manifest in the protein primary structure, but appear, apparently, as a hidden factor, which causes the low effectiveness of classical influenza vaccines. The identification of several limitations in gene structure suggests that its any modification (in any gene) must not contradict each of the restrictions established by nature. The frequency of CpG dinucleotides in all studied strains is low, but a potential for optimizing it in H1N1 strains due to the prohibition of the quartet in the gene for arginine-encoding codons is especially limited and can be implemented through synonymous codons of other amino acids (alanine, proline, threonine or serine). Compared to the H1N1 subtype, the H3N2 subtype can be expected to have more possibilities in constructing stable NA gene mRNA.

Russian Journal of Infection and Immunity. 2024;14(4):709-718
pages 709-718 views

Influenza and non-influenza ARVI in children. A relationship between cytokine profile, parameters of the “lipid peroxidation – antioxidant defense system” as well as clinical and laboratory indicators

Darenskaya M.A., Kazantseva E.D., Petrova A.G., Rychkova L.V., Kolesnikov S.I., Semenova N.V., Kurashova N.A., Lesnaya A.S., Sholokhov L.F., Kolesnikova L.I.

Abstract

Influenza and acute respiratory viral infections (ARVI) impose a substantial damage to the population health in the Russian Federation due to their seasonal circulation and predominantly affect young children. A very few data on the cytokine profile, the nonspecific LPO — AOD system and their relationships with clinical characteristics in such diseases in preschool children are available. The aim of this study was to assess the cytokine profile, LPO — AOD system parameters and their relationship with the clinical and laboratory characteristics of diseases in preschool children with influenza and other ARVI. 86 preschool children (3–6 years old) were examined: with an established diagnosis of influenza (n = 31), non-influenza ARVI (n = 28), apparently healthy children (control group (n = 27). All pediatric samples were analyzed by enzyme-linked immunosorbent assay assessing blood serum concentrations of C-reactive protein and cytokines IL-1β, IL-4, IL-6, IL-8, TNFα, IFNα, IFNγ. Spectrophotometric, fluorometric and enzyme immunoassay methods to assess the state of the “LPO — AOD” system were used. In the group of children with influenza vs other ARVI, a higher incidence of intoxication syndrome was revealed. Cytokine profile in children from both clinical groups compared with control cohort was featured with higher indicators of both pro-inflammatory and anti-inflammatory origin. Children with non-influenza ARVI, had increased magnitude of LPO final products in the nonspecific LPO — AOD system along with lowered concentration of fat-soluble vitamins, general antioxidant activity, GSH level, and SOD activity. In the group with influenza, the level of primary and final lipid peroxidation products was increased, whereas that of for retinol, α-tocopherol, and total antioxidant activity was decreased paralleled with higher GSSG and SOD levels. Numerous correlations were noted in the group of children with ARVI: IL-1β/ketones, IL-6/ketones, IL-8/ketones, TNFα/ketones, IL-4/ketones, IFNg/shortness of breath, IFNα/cough, double bonds/fever, double bonds/AST, SO/intoxication, retinol/fever, GSSG/cough. The influenza group differed in the following relationships: IL-4/ketones, IL-4/fever, IFNα/ketones, CDs/AST. It can be concluded that in preschool children with ARVI and influenza, changes in the cytokine profile are accompanied by increased pro- and anti-inflammatory cytokine levels, increased intensity of lipid peroxidation reactions along with reduced magnitude of antioxidant factors. In the group with ARVI, there was a relationship between the final toxic products of lipid peroxidation — Schiff bases — and the intoxication index, as well as the presence of protective mechanisms in the form of connections between interferons and disease clinical manifestations. The group with influenza was distinguished by the presence of protective relations, which may have a beneficial effect in the context of developing pathological process. The data obtained will help expand the understanding of the pathogenetic mechanisms related to immune reactivity and nonspecific lipid peroxidation reactions in preschool patients and formulate appropriate measures for correction.

Russian Journal of Infection and Immunity. 2024;14(4):719-730
pages 719-730 views

Altered leukocyte blood count in COVID-19 pandemic period

Kostarev S.N., Sereda T.G.

Abstract

Relevance. A potential for zoonotic transmission of highly pathogenic coronavirus strains to humans was of little concern to health care providers, which came as a surprise and led to a coronavirus pandemic in 2020 spring. In 2023 fall, there was higher number of humans infected with coronavirus infection. In 2024, influenza outbreaks characterized by wave-like temperature changes are observed, which may indicate the emergence of a new virus strain. Currently, it is of interest to study the effects related to novel coronavirus infection on human immune system. To date, the immune responses for individual parameters from leukocyte blood formula have been studied, but insufficient attention has been paid to the cumulative impact, due to the fact that many parameters behave ambiguously and it has not been possible to determine the cumulative impact on the immunogram. The aim of the study is to investigate models describing the dynamics in immunogram changes during the pandemic in adolescents living in Perm Krai. The objectives were to analyze differential equations describing a change in immunogram parameters; to summarize study results on impaired immunity due to exposure to coronavirus infection. Results. Differential equations were analyzed and the extremum and age patient parameters with the greatest deviation from the reference interval were determined. Conclusion. Despite the fact that individual elements of flow cytophotometric analysis are oscillatory in nature with large impulses, the generalization of flow cytophotometric analysis indices showed an interesting pattern characterized by a smooth change towards increasing deviation in older adolescence for all studied parameters. Flow cytophotometric analysis indices being within the reference range had the same modality towards negative trend with increasing age only differed by the fact that in the disease state the deviation was twice as large. Without disease, the excess of flow cytophotometric analysis indicators had a positive trend with increasing age, and the decrease of flow cytophotometric analysis indicators from the reference interval had a negative trend. In the disease state with decreased immunoglobulins, when flow cytophotometric analysis exceeded the reference interval, there was a convex deviation in the negative direction with increasing age. When decreasing from the reference interval, a convex curve with a positive trend is observed. Upon elevated immunoglobulins exceeding the reference interval flow cytophotometric analysis has a convex positive trend, whereas for at lowering the reference interval flow cytophotometric analysis also has a convex positive trend exceeding 5 times.

Russian Journal of Infection and Immunity. 2024;14(4):731-739
pages 731-739 views

The effect of a new coronavirus infection on hemogram parameters in the early convalescence period of patients with coronary heart disease

Agarkov N.M., Yakunchenko T.I., Okhotnikov O.I., Makkonen K.F., Alymova M.V.

Abstract

Laboratory data, especially a general blood test, play an important role in the treatment of infectious diseases, including COVID-19. However, in patients with coronary heart disease (CHD) and COVID-19, a general blood test is rarely analyzed and is insufficient to fully assess an impact of the new coronavirus infection on patients with cardiac diseases. The aim of the study was to analyze a COVID-19 effect on hemogram parameters in the early recovery period of patients with coronary heart disease. The study was performed at the Kursk City Clinical Hospital for Emergency Medical Care in the years 2021–2022, which involved 58 mature-aged patients (45–59 years old) suffering from coronary heart disease who had a new coronavirus infection and 62 elderly patients suffering from coronary heart disease alone. Morning blood sampling was carried out from the forearm superficial veins into Vacutainer test tubes added with a coagulation activator. In elderly patients, 3–4 weeks after recovery, significant changes in red blood parameters persisted — a decline in the level of peripheral blood erythrocytes, hemoglobin and hematocrit. Elderly patients with coronary heart disease comorbid with a moderate new coronavirus infection, 3–4 weeks later had also higher count of leukocytes, neutrophils, segmented neutrophils and ESR level relative to comparison group. It should be noted that in the early convalescence period elderly patients with coronary heart disease and COVID-19 had significantly elevated ESR, which confirms ongoing sustained inflammatory process. After evaluating the information content according to the calculated Kullback informativeness assessment for analyzed general blood test parameters, it was found to peak for platelet and leukocyte counts as well as ESR level. Thus, among the analyzed indicators in the general blood test, it turned out that platelet and leukocyte count along with ESR level were most informative and of prognostic significance during early convalescent period of elderly patients with coronary heart disease comorbid with a new coronavirus infection, which are proposed to be used as biomarkers of early convalescent period.

Russian Journal of Infection and Immunity. 2024;14(4):740-746
pages 740-746 views

Human body resistance dynamics in the post-covid period

Zhdanova E.V., Rubtsova E.V., Kostolomova E.G.

Abstract

The issue of the state of specific and nonspecific resistance in the post-COVID period and the possible consequences of COVID-19 remains poorly understood. A clinical and laboratory examination of 124 patients was conducted at various time points after COVID-19 infection. 62 patients recovered completely and 62 had post-COVID syndrome. The leukocyte count and leukogram were evaluated in all patients. Immunogram parameters were additionally evaluated in patients with post-COVID syndrome. The results showed that, regardless of post-COVID syndrome, leukocyte count is lower in all patients within six months after COVID-19 infection than in unaffected subjects. The absolute neutrophil count is restored only 12 months later. In the presence of post-COVID syndrome, the absolute number of CD3+, CD4+ and CD19+ lymphocytes was lower than in healthy people. At the same time, 3 to 15 months after that, IgA titer in patients with PCS was significantly lower and that of for total IgM and IgG was higher without any clinical or laboratory signs of inflammation. The total blood IgE level was significantly higher and increased by the end of the observation period. A decreased activity of nonspecific protection, as well as indicators of cellular and humoral immunity in patients with post-COVID syndrome is accompanied by higher rate of viral and bacterial infections of various localization. Whereas during the first period an increase in total blood ID is not accompanied by clinical signs of atopy, then 6 months later the frequency of allergy increases. During the same period, cases of a joint syndrome revealed as arthralgia or progressive joint destruction become more frequent. Atopic manifestations are often combined with joint syndrome. Thus, after a COVID-19 infection, a low long-term level of nonspecific protection remains in vivo. In patients with post-COVID syndrome, low nonspecific and specific body resistance is manifested by viral and bacterial infections of the mucous membranes and skin. An imbalance in the immune system contributes to developing allergic and autoimmune processes.

Russian Journal of Infection and Immunity. 2024;14(4):747-755
pages 747-755 views

Alterations in T cell immunity over 6–12 months post-COVID-19 infection in convalescent individuals: a screening study

Zurochka A.V., Dobrynina M.А., Safronova E.A., Zurochka V.A., Zuikova A.A., Sarapultsev G.P., Zabkov O.I., Mosunov A.A., Verkhovskaya M.D., Ducardt V.V., Fomina L.O., Kostolomova E.G., Ostankova Y.V., Kudryavtsev I.V., Totolian A.A.

Abstract

Acute COVID-19 is a viral infection caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in dramatically decreased peripheral blood CD3+ T cell count apparently due to alterations of thymic T cell maturation, that can persist long term afterwards. Therefore, we analyzed the levels of peripheral blood TRECs (T-cell receptor excision circles), and investigated the main alterations in peripheral blood T cell subsets in COVID-19 convalescents. We performed molecular quantification of TRECs with “TREC/KREC-AMP PS” kit and flow cytometric analysis of peripheral blood lymphocytes from three groups of patients. The first group contained 109 samples from COVID-19 convalescents (6–12 month post-acute COVID-19) with normal levels of TRECs (TRECn); the second was formed from COVID-19 convalescents (6–12 month post-acute COVID-19) with decreased levels of TRECs (TREClow, n = 29), and healthy control group (HC, n = 18). We noticed no significant differences between all three groups in CD3+ T cell relative and absolute numbers. However, CD4+ T cell frequencies were decreased in TREClow and TRECn groups compared to HC (40.8% (31.6; 50.1) and 46.4% (40.0; 53.0) vs 53.5% (47.36; 56.9), p < 0.001 and р = 0.004, respectively). Furthermore, Th cell levels were decreased in TREClow patients vs HC and TRECn groups (701 cell/1 µL (478; 807) vs 1005 cell/1 µL (700; 1419), р = 0.020, and 876 cell/ 1 µL (661; 1046), р = 0.008, respectively). Finally, both groups of COVID-19 convalescents had increased frequencies of circulating CD8+ T cells — 29.4% (20.7; 39.7) in TREClow group, 26.5% (21.1; 32.7) in TRECn group vs 21.3% (17.1; 26.0) in healthy controls (p = 0.024 and р = 0.026, respectively). In TRECn group, CD8+ T cell count was elevated vs control range (508 cell/1 µL (372; 622) vs 356 cell/1 µL (247; 531), р = 0.044). Thus, COVID-19 convalescents (6–12 month post-acute COVID-19) showed an imbalance in CD4+ and CD8+ T cell level even at 6–12 months post-acute SARS-CoV-2 infection, and the observed changes in peripheral blood T cells could be closely related to the alterations in thymic T cell maturation and differentiation. Such a long-term decline in TREC levels in the circulation may have a profound impact on immune system functions and requires immunocorrection therapy.

Russian Journal of Infection and Immunity. 2024;14(4):756-768
pages 756-768 views

Post-vaccination immunity and pneumonia incidence in medical workers in response to various flu vaccination regimens between the 1st and 2nd peaks of COVID-19 morbidity

Kostinov M.P., Nastaeva N.Y., Nikityuk N.F., Mashilov K.V., Khasanova A.A., Solovyeva I.L., Andreeva N.P., Li Y.А., Polishchuk V.B., Linok A.V., Loktionova M.N., Kostinova A.M., Khrapunova I.A.

Abstract

Background. In the absence of a vaccine against SARS-CoV-2, seasonal influenza vaccination during the pandemic contributed to lowered COVID-19 susceptibility and severity. The study was aimed to assess the state of post-influenza vaccination immunity, pneumonia frequency and severity in medical workers after using various flu vaccination regimens, between the 1st and 2nd peaks of COVID-19 epidemic rise. Materials and methods. Comparatively analyzed data on the levels of antibodies against influenza virus strains and pneumonia incidence in 487 medical workers was carried out: 1st group — unvaccinated in 2020–2021 (n = 281), 2nd group — vaccinated against influenza (Sovigripp), (n = 98), 3rd group — received combined vaccination against influenza and pneumococcus (Prevenar 13), (n = 108). Results. 6 months after vaccination, the highest rates of influenza virus were detected in the A(H3N2), the level of seroprotection (≥ 1:40) ranged from 49.0% in unvaccinated (1st group) to 53.4–53.2% in those who received combined vaccination (group III), as well as influenza alone (2nd group), p > 0.05; for strain A(H1N1) the level of seroprotection in 1st group is 24.5%, lower (p < 0.04) than in 2nd group — 32.7%, but does not differ from the levels of 40.4% in group III; for strain B the level of seroprotection is the lowest ranging from 19.4% in the group of unvaccinated subjects up to 22.4% in 2nd group and 23.4% in 3rd group. The pneumonia incidence in 1st group (3.9%), 2nd group (3.1%), 3rd group (4.6%) did not differ, however, among all vaccinated subjects severity of pneumonia clinical course was mild, whereas in unvaccinated employees, except for mild course (45.4%, 5 out of 11 people) pneumonia in 36.4% (4 out of 11 people) cases was assessed as moderate and in 18.2% (2 out of 11 people) cases — severe with fatal outcomes. Conclusion. The study showed that 6 months after seasonal influenza immunization between the 1st and 2nd peaks of COVID-19 epidemic rise, the immunogenicity of the vaccine meets the CPMP criterion for the A(H3N2) strain. In vaccinated patients, the proportion of pneumonia with COVID-19 clinical picture was mild in 100% of cases, and in unvaccinated patients in 36.4% of cases — of moderate severity and in 18.2% — severe with fatal outcome.

Russian Journal of Infection and Immunity. 2024;14(4):769-780
pages 769-780 views

Immunogenicity and safety of DTPW-HEPB-HIB (PRP-T) vaccine (Pentavac) in infants aged 2–7 months: a post marketing phase 4 clinical trial study

Masoumi-Asl H., Nateghian A., Baradaran H., Jafari E., Azizian R., Faramarzi M.

Abstract

Background. Vaccines play a critical role in safeguarding public health, particularly for children. It is imperative to proactively address safety concerns to uphold trust in their effectiveness and safety. Skepticism surrounding vaccines can have significant adverse effects on the overall well-being of the entire population, potentially leading to individuals opting out of vital vaccinations, thereby posing risks to public health. Thus, ensuring confidence in vaccine safety remains paramount. Materials and methods. This phase four clinical trial was conducted as a post-marketing study (PMS) on 2 to 7 month old healthy infants (N = 539) to evaluate immunity and safety of Indian pentavalent vaccine containing Diphtheria, Tetanus, Pertussis, Hepatitis B and Haemophilus influenza type b [DTPW-HEP B-HIB (PRP-T)/PENTAVAC] in four different centers at Tehran province. Blood samples were collected from eligible infants before receiving the vaccine (2 months of age) and 1 month after the third dose (7 months of age) to determine antibodies against all antigens in the pentavalent vaccine using ELISA. Results. The results indicated that the immune responses demonstrated seroprotection and protective antibody levels after three doses of the vaccine for Haemophilus influenza b, diphtheria, tetanus, hepatitis B virus and Bordetella pertussis were 99.1%, 98.7%, 99.8%, 99.4% and 69.6%, respectively. Statistical analysis showed that the P-value for all vaccine components was similar (P < 0.001). The five most common side effects reported were mild fever (10%), erythema at the vaccination site (9.1%), inflammation (4.3%), pain at the vaccination site (3.3%), and restlessness (2.6%). Conclusion. This study’s findings demonstrated a significant increase in antibody levels against all five vaccine components. In light of these results, it can be concluded that the Pentavalent vaccine is not only effective in enhancing immunity against multiple diseases but also presents minimal risk of side effects in the study population. These findings contribute to the body of evidence supporting the safety and efficacy of vaccines, underscoring their crucial role in protecting public health.

Russian Journal of Infection and Immunity. 2024;14(4):781-787
pages 781-787 views

Antibody titer after anti-idiotype rabies vaccination with nano-chitosan adjuvant

Paryati S.P., Ramadhanti S., Hasan K.

Abstract

Background. The rabies virus neutralizing antibodies titers is a public health problem in the world, including Indonesia. Rabies is zoonotic and causes death in humans with a case fatality rate of 100%. Anti-idiotype antibody (Ab2) from chicken immunoglobulin (IgY) can be a substitute antigen for the rabies virus. This research aims to study the potential of rabies vaccine based on anti-idiotype antibody (Ab2) with nano-chitosan as an adjuvant. Materials and methods. The production of Ab2 is derived from purified and characterized chicken immunoglobulins. Nano-chitosan is made from chitosan from shrimp shell waste. Vaccination tests were carried out on rats compared with commercial vaccines as a positive control and physiological solutions as a negative control. The characterization results of IgY Ab2 were IgY rabies with BM ~180 kDa, heavy chains (BM ~60 kDa), and light chains (BM ~30 kDa) of IgY. Nano-chitosan is less than 100 nm in size, can dissolve well, and does not cause side effects in experimental animals. Results. The vaccine formula uses a concentration of 0.5%, where the ratio of nano-chitosan and Ab2 is 1:1. The Ab2 concentration used was about 1000 units per mL of the Ab2 suspension. Conclusion. This study concludes that anti-idiotype antibodies dissolved in nano-chitosan adjuvant can induce the formation of antibodies with titers that are not statistically different from the antibody titers induced by commercial rabies vaccines. Nano-chitosan has a potential vaccine adjuvant candidate, safe to use, and can enhance the immunogenicity of an antigen applied subcutaneously. According to the results of this study, it is recommended that post-vaccination antibody titers be measured regularly: for example, every one week for six weeks after vaccination. This measurement determines the time of the peak of the antibody titer so that the time for revaccination can be determined.

Russian Journal of Infection and Immunity. 2024;14(4):788-794
pages 788-794 views

HIV protein profile characteristics in patients with first-time detected infection

Davydenko V.S., Ostankova Y.V., Schemelev A.N., Serikova E.N., Totolian A.A.

Abstract

The HIV-infection continues to be one of the most large-scale epidemics worldwide. Many techniques have been developed to detect this disease, but the Western blot based on the identification of specific viral proteins remains the most commonly used method that allows to monitor ongoing viral processes. Despite discussions regarding the criteria for a positive test assessment and selection of a minimum number of viral proteins to reliably interpret the data, a very few studies on the protein profiles in HIV-infected patients, particularly in the Russian Federation are available. The aim of this study was to assess the prevalence of HIV viral proteins in a group of people with newly diagnosed infections analyzing 2566 blood samples from individuals with newly diagnosed HIV infection for reference testing. The samples were assessed using ELISA and IHL techniques, followed by western blotting. Subsequently, the following viral proteins were analyzed to assess HIV life cycle and the predominance of its different stages: gp160, gp120, gp41, p55, p40, p24, p17, p66, p51, and p31. For comparison, gp110/120 was chosen as the reference protein due to its lowest prevalence frequency among all env gene products comprising 96.06%. A significantly reduced prevalence frequency was found for several protein groups: GAG — p55 (80.91%), p40 (72.14%), nucleocapsid p18/17 (67.37%); POL proteins — p68/66 (89.57%), p52/51 (81.91%), p34/31 (86.02%). Significant differences in frequency of viral proteins between age and sex groups are shown. Hypotheses explaining the obtained data are presented. By aligning anti-viral protein antibody profile with the course of the infection and patient’s condition, it will be possible to identify patterns and take necessary measures for early diagnostics with extended results, such as duration of the infection, viral load, and disease severity.

Russian Journal of Infection and Immunity. 2024;14(4):795-808
pages 795-808 views

Prevalence and antibiotics susceptibility of thermotolerant Campylobacter spp. isolated from humans and chickens in the Republic of Guinea

Balde R., Matveeva Z.N., Kaftyreva L.A., Makarova M.A.

Abstract

Background. The issue of diarrheal diseases remains relevant for modern health care in all countries. Campylobacteriosis is the most common infectious disease with foodborne transmission and poultry meat is a transmission factor. Materials and methods. 724 items of faeces sampled from patients with diarrheal syndrome and 283 samples of faeces of chickens raised on private farms and five poultry farms in the province were studied. For bacteriological method were used selective media. Traditional routine tests (cell morphology, cytochrome oxidase, catalase, hydrolysis of sodium hippurate and indoxyl acetate) and MALDI-ToF mass spectrometry was performed for identification. The susceptibility of strains to antibiotics was analysed using the disc-diffusion method. Results were interpreted according to the EUCAST criteria, versions 2019–2022. Results. Campylobacter spp. was cultured in 65 out of 724 faecal samples from patients with acute diarrhoea, of them 83.08% were identified as C. jejuni, and 16.92% as C. coli. Of the 237 Campylobacter strains from chicken were identified as C. jejuni (54.0%), as C. coli (46.0%). Campylobacter spp. strains from humans were resistant to tetracycline (40.0%), to erythromycin (6.15%), to ciprofloxacin (12.31%). The strains from chickens kept on farms, were resistant to tetracycline in 42.55%, to ciprofloxacin — in 22.70% and to erythromycin — in 11.35%. The strains from chickens kept on private farms were resistant to tetracycline in 4.17%, to ciprofloxacin — in 1.04%, all strains were sensitive to erythromycin. Conclusion. Thus, due to the widespread prevalence of Campylobacter spp., infectious diseases they cause remain a topical issue. Studying the resistance to antibiotics in Campylobacter spp. among poultry could allow to develop new approaches to confirming the significance of their foodborne nature and to improve the national disease prevention system.

Russian Journal of Infection and Immunity. 2024;14(4):809-815
pages 809-815 views

SHORT COMMUNICATIONS

Opisthorchiasis-related topical issues

Ryabenko Y.N., Ryabenko E.B.

Abstract

The article analyzes statistical data on the 2020 vs 2019 opisthorchiasis incidence rate on the territory of the Russian Federation and in foreign countries, provides absolute and intensive morbidity indicators across entire the Russian Federation and specifically in its subjects — republics and regions, general prevalence of helminthiasis, and opisthorchiasis particularly overall pattern of parasitic diseases, as well as contribution of opisthorchiasis to general pattern of biohelminthiasis, its dynamics, and prevalence of relevant causative agent. A comparative analysis for incidence rates in the regions where opisthorchiasis was recorded and mean country-wide statistical parameters was carried out. As a result, it was concluded that despite a decline in the Russia-wide overall parasitic morbidity, an excess of mean indicators, sometimes significant, was noted in some regions. Thus, compared to Russia-wide magnitude of intensive indicator, it was higher by 4-fold in the Komi Republic, whereas in the Kurgan, Vologda, Arkhangelsk Regions and the Nenets Autonomous Okrug — by 3-fold. The article provides an analysis of the population age groups as well as percentage of opisthorchis-affected urban and rural populations. In addition, the special clinical and epidemiological significance of opisthorchiasis remains urgent due to severity of its course, affected various body systems and organs, emergence of serious complications leading to disability, and in some cases to fatal outcomes, the presence of natural foci, most of which are located in the Russian Federation. Almost all territories adjacent to the basins of the Ob, Irtysh, Tom rivers and their tributaries pose special concern regarding opisthorchiasis. The data related to prevalence of helminthiasis larvae detected in fish in 2020 and 2019 since 2010 are presented. Based on the data shown above, strict adherence to preventive measures plays an important role in reducing opisthorchiasis incidence rate and preventing its spread.

Russian Journal of Infection and Immunity. 2024;14(4):816-822
pages 816-822 views

Serotonin and adrenaline as inhibitors of neutrophil extracellular traps formation (experimental study)

Skupnevskiy S.V., Saveljev R.V.

Abstract

Regulation of the NETosis can provoke cancer, inflammatory and autoimmune diseases and become a basis for effective targeted therapy. The aim: to study the modifying effects of serotonin and adrenaline on NETosis during phagocytosis in rats. Materials and methods. Wistar rats were divided into control (solvent, 0.9% NaCl solution) and experimental (serotonin and adrenaline 1.43 and 0.143 mg/kg body weight, respectively) groups. Intraperitoneal injection of test substances was carried out 90 minutes before blood sampling, in which phagocytic activity (PhA), phagocytic index (PhI) and degree of suicidal neutrophil NETosis were determined: with total and partial chromatin decondensation (TCD, PCD, accordingly). A paired Student’s t test was used to compare groups with numerical values and McNemar’s test (for dichotomous variables). Pearson’s linear correlation coefficient (rxy) was assessed to measure a linear relationship between time points. Results. The administration of adrenaline contributed to NETosis inhibition by 41.5% compared to control group (p < 0.001), serotonin — by 27.6% (p < 0.001). The ratio of neutrophils with total and partial chromatin decondensation for control group was 1.0:0.9; for serotonin and adrenaline it changed to 1.0:1.7 and 1.0:1.4, respectively. Relative to control group, phagocytic index after serotonin administration increased by 4.9%, in case of adrenaline, on the contrary, it decreased by 12.4% (p < 0.01). A high positive correlation was revealed between NETosis and phagocytic index for control group and experimental group with adrenaline: rxy = 0.823–0.997. For phagocytic index and NETosis in these groups there was a high negative (rxy = –0.714–(–0.871)) and a noticeable positive correlation for serotonin (rxy = 0.638). Conclusion. Serotonin and adrenaline in therapeutic dosages have a pronounced inhibitory effect on NETosis, which may pave the avenue for increasing the effectiveness of therapy for immunoinflammatory and oncological diseases. The use of serotonin is preferable because it has additional immunomodulatory effects and cause no direct stimulation of α- and β-adrenergic receptors.

Russian Journal of Infection and Immunity. 2024;14(4):823-826
pages 823-826 views

Laboratory support for seromonitoring of anti-pertussis post-vaccination immunity

Vidmanova M.V.

Abstract

Monitoring of humoral immunity in 3–4 year-old anti-pertussis vaccinated children is one of the approaches for pertussis epidemiological surveillance. It’s a predictive indicator for comprehensive assessment of morbidity in the region. The agglutination reaction (RA) used earlier has been displaced with enzyme immunoassay (ELISA). So, two questions arose: regarding i) a relevance of using ELISA in whole-cell vaccinated individuals, and ii) correctness of large-scale data interpretation without applying a unified IgG reference value. Study aims were to assess humoral anti-pertussis population immunity by ELISA, to determine features of humoral protection in vaccinated subjects after using various vaccine types, to identify age features, to make recommendations for evaluating seromonitoring data. Blood serum samples from anti-pertussis vaccinated children in Samara region (n = 1729) were examined in 2016–2020; children were divided into 4 age groups (< 3, 3–4, 5–7, ≥ 7.1 years) and into 3 type vaccines groups: cellular, acellular and combined. We used two ELISA kits, which are designed to assess post-vaccination immunity, according to the manufacturer’s instructions, quantifying IgG against B. pertussis, which differ in units and reference values. Statistical analysis was performed using StatTech program v.2.6.2. The largest and smallest percentage of seronegative children was in the cellular-vaccinated and acellular-vaccinated group, respectively. Seronegative percentage in the “indicator group” reaches 55.2% being significantly higher than acceptable 10.0%-level, and differs from the literature data (30–40%), which were obtained mainly with RA. This may suggest about an incorrect interpretation of post-vaccination immunity data evaluation strictly according to manufacturers’ reference criteria, especially for whole-cell vaccinated subjects. A method for calculating the seronegative percentage is proposed that relies on the prognostic negative data level as a correction factor. The required values were obtained during comparison studies of random serum samples from 3–4-year-old children (n = 70) using two ELISA kits (“RIDASCREEN® Bordetella”, “SeroPertussis™ IgG”) and intra-laboratory comparison panel. It should be given preference for sets with a greater prognostic negative data level, if population seronegative percentage is assessed.

Russian Journal of Infection and Immunity. 2024;14(4):827-832
pages 827-832 views


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