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4,632 results on '"Ishmukhametov A"'

4. Deep Active Learning with Concept Drifts for Detection of Mercury’s Bow Shock and Magnetopause Crossings

Author

Julka, Sahib, Ishmukhametov, Rodion, Granitzer, Michael, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Nicosia, Giuseppe, editor, Ojha, Varun, editor, La Malfa, Emanuele, editor, La Malfa, Gabriele, editor, Pardalos, Panos M., editor, and Umeton, Renato, editor

Published
2024
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5. Structural diversity of tick-borne encephalitis virus particles in the inactivated vaccine based on strain Sofjin

Author

Andrey Moiseenko, Yichen Zhang, Mikhail F. Vorovitch, Alla L. Ivanova, Zheng Liu, Dmitry I. Osolodkin, Alexey M. Egorov, Aydar A. Ishmukhametov, and Olga S. Sokolova

Subjects
Tick-borne encephalitis virus, inactivated vaccines, cryoelectron microscopy, image analysis, variability analysis, asymmetry, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

ABSTRACTThe main approach to preventing tick-borne encephalitis (TBE) is vaccination. Formaldehyde-inactivated TBE vaccines have a proven record of safety and efficiency but have never been characterized structurally with atomic resolution. We report a cryoelectron microscopy (cryo-EM) structure of the formaldehyde-inactivated TBE virus (TBEV) of Sofjin-Chumakov strain representing the Far-Eastern subtype. A 3.8 Å resolution reconstruction reveals the structural integrity of the envelope E proteins, specifically the E protein ectodomains. The comparative study shows a high structural similarity to the previously published structures of the TBEV European subtype strains Hypr and Kuutsalo-14. A fraction of inactivated virions exhibits asymmetric features including the deformations of the membrane profile. We propose that the heterogeneity is caused by inactivation and perform a local variability analysis on the small parts of the envelope protein shell to reveal membrane curvature features possibly induced by the inactivation. The results of this study will have implications for the design of novel vaccines against diseases caused by flaviviruses.

Published
2024
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6. The structure of inactivated mature tick-borne encephalitis virus at 3.0 Å resolution

Author

Evgeny B. Pichkur, Mikhail F. Vorovitch, Alla L. Ivanova, Elena V. Protopopova, Valery B. Loktev, Dmitry I. Osolodkin, Aydar A. Ishmukhametov, and Valeriya R. Samygina

Subjects
Cryo-electron microscopy, inactivated vaccines, structural virology, tick-borne encephalitis virus, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

ABSTRACTTick-borne encephalitis virus (TBEV) causes a severe disease, tick-borne encephalitis (TBE), that has a substantial epidemiological importance for Northern Eurasia. Between 10,000 and 15,000 TBE cases are registered annually despite the availability of effective formaldehyde-inactivated full-virion vaccines due to insufficient vaccination coverage, as well as sporadic cases of vaccine breakthrough. The development of improved vaccines would benefit from the atomic resolution structure of the antigen. Here we report the refined single-particle cryo-electron microscopy (cryo-EM) structure of the inactivated mature TBEV vaccine strain Sofjin–Chumakov (Far-Eastern subtype) at a resolution of 3.0 Å. The increase of the resolution with respect to the previously published structures of TBEV strains Hypr and Kuutsalo-14 (European subtype) was reached due to improvement of the virus sample quality achieved by the optimized preparation methods. All the surface epitopes of TBEV were structurally conserved in the inactivated virions. ELISA studies with monoclonal antibodies supported the hypothesis of TBEV protein shell cross-linking upon inactivation with formaldehyde.

Published
2024
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9. Investigation of oncolytic potential of vaccine strains of yellow fever and tick-borne encephalitis viruses against glioblastoma and pancreatic carcinoma cell lines

Author

Alina S. Nazarenko, Yulia K. Biryukova, Ekaterina O. Orlova, Kirill N. Trachuk, Alla L. Ivanova, Alla V. Belyakova, Nikolai B. Pestov, Mikhail F. Vorovitch, Aydar A. Ishmukhametov, and Nadezhda M. Kolyasnikova

Subjects
oncolytic viruses, flaviviruses, yellow fever virus, tick-borne encephalitis virus, glioblastoma cell, pancreatic carcinoma cell, virus sensitivity, viral oncolysis, Microbiology, QR1-502
Abstract

Introduction. Flaviviruses, possessing natural neurotropicity could be used in glioblastoma therapy using attenuated strains or as a delivery system for antitumor agents in an inactivated form. Objective. To investigate the sensitivity of glioblastoma and pancreatic carcinoma cell lines to vaccine strains of yellow fever and tick-borne encephalitis viruses. Materials and methods. Cell lines: glioblastoma GL-6, T98G, LN-229, pancreatic carcinoma MIA RaCa-2 and human pancreatic ductal carcinoma PANC-1. Viral strains: 17D yellow fever virus (YF), Sofjin tick-borne encephalitis virus (TBEV). Virus concentration were determined by plaque assay and quantitative PCR. Determination of cell sensitivity to viruses by MTT assay. Results. 17D YF was effective only against pancreatic carcinoma tumor cells MIA Paca-2 and had a limited effect against PANC-1. In glioblastoma cell lines (LN229, GL6, T98G), virus had no oncolytic effect and the viral RNA concentration fell in the culture medium. Sofjin TBEV showed CPE50 against MIA Paca-2 and a very limited cytotoxic effect against PANC-1. However, it had no oncolytic effect against glioblastoma cell lines (LN229, T98G and GL6), although virus reproduction continued in these cultures. For the GL6 glioblastoma cell line, the viral RNA concentration at the level with the infection dose was determined within 13 days, despite medium replacement, while in the case of the LN229 cell line, the virus concentration increased from 1 × 109 to 1 × 1010 copies/ml. Conclusion. Tumor behavior in organism is more complex and is determined by different microenvironmental factors and immune status. In the future, it is advisable to continue studying the antitumor oncolytic and immunomodulatory effects of viral strains 17D YF and Sofjin TBEV using in vivo models.

Published
2023
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10. The role of the encephalomyocarditis virus type 1 proteins L and 2A in the inhibition of the synthesis of cellular proteins and the accumulation of viral proteins during infection

Author

Yury Yu. Ivin, Anna A. Butusova, Ekaterina E. Gladneva, Galina Ya. Kolomijtseva, Yusuf K. Khapchaev, and Aydar A. Ishmukhametov

Subjects
emcv-1, cardioviruses, picornaviruses, «security» proteins, leader protein, 2a, translation inhibition, processing, Microbiology, QR1-502
Abstract

Introduction. Infection of cells with encephalomyocarditis virus type 1 (EMCV-1, Cardiovirus A: Picornaviridae) is accompanied by suppression of cellular protein synthesis. The main role in the inhibition of cellular translation is assigned to the L and 2A «security» proteins. The mechanism of the possible influence of the L protein on cellular translation is unknown. There are hypotheses about the mechanism of influence of 2A protein on the efficiency of cap-dependent translation, which are based on interaction with translation factors and ribosome subunits. However, the available experimental data are contradictory, obtained using different approaches, and do not form a unified model of the interaction between the L and 2A proteins and the cellular translation machinery. Aim. To study the role of L and 2A «security» proteins in the suppression of translation of cellular proteins and the efficiency of translation and processing of viral proteins in infected cells. Materials and methods. Mutant variants of EMCV-1 were obtained to study the properties of L and 2A viral proteins: Zfmut, which has a defective L; Δ2A encoding a partially deleted 2A; ZfmutΔ2A containing mutations in both proteins. Translational processes in infected cells were studied by Western-blot and the pulse method of incorporating radioactively labeled amino acids (14C) into newly synthesized proteins, followed by radioautography. Results. The functional inactivation of the 2A protein does not affect the inhibition of cellular protein synthesis. A direct correlation was found between the presence of active L protein and specific inactivation of cellular protein synthesis at an early stage of viral infection. Nonspecific suppression of the translational processes of the infected cell, accompanied by phosphorylation of eIF2α, occurs at the late stage of infection. Partial removal of the 2A protein from the EMCV-1 genome does not affect the development of this process, while inactivation of the L protein accelerates the onset of complete inhibition of protein synthesis. Partial deletion of the 2A disrupts the processing of viral capsid proteins. Suppression of L protein functions leads to a decrease in the efficiency of viral translation. Conclusion. A study of the role of EMCV-1 L and 2A proteins during the translational processes of an infected cell, first performed using infectious viral pathogens lacking active L and 2A proteins in one experiment, showed that 2A protein is not implicated in the inhibition of cellular translation in HeLa cells; L protein seems to play an important role not only in the specific inhibition of cellular translation but also in maintaining the efficient synthesis of viral proteins; 2A protein is involved not only in primary but also in secondary processing of EMCV-1 capsid proteins.

Published
2023
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11. Perspectives for applying Alphaviruses in antitumor therapy

Author

Alina S. Nazarenko, Yulia K. Biryukova, Nadezhda M Kolyasnikova, Mikhail F. Vorovich, Nikolai B. Pestov, and Aidar A. Ishmukhametov

Subjects
oncolytic viruses, alphaviruses, virotherapy, immunotherapy, viral vector, recombinant virus, cancer immunotherapy, Infectious and parasitic diseases, RC109-216
Abstract

Oncolytic viral therapy is a promising approach for treating tumors. Oncolytic viruses can directly lyse tumor cells and indirectly activate antitumor immunity. Alphaviruses, as oncolytic viruses, are particularly promising agents because they can selectively infect and lyse tumor cells, modulate microtumor environment, elicit immune-mediated lysis of tumor cells, and serve as a platform for transgene delivery. To ensure safety, attenuated strains of Alphaviruses are typically used for genetic engineering, and immunogenic tumor-associated antigens or cytokines are commonly chosen as transgenes. Studies evaluating both in vitro and in vivo oncolytic and immunomodulatory effects of Alphaviruses and vectors based on them have been growing exponentially. Animal models of various tumor types were used to examine the effectiveness of Alphaviruses, including Sindbis, Semliki Forest virus, Geta (strain M1), Venezuelan equine encephalitis virus, and vectors based on them. Additionally, Alphaviruses revealed enhanced antitumor activity while used in combination therapies with other oncolytic viruses. Alphavirus-like replicon particles based on attenuated Venezuelan equine encephalitis virus may serve for transgene delivery to express heterologous proteins at high levels, and induce both humoral and cellular immune responses. An alphaviral vector-based vaccine, encoding the HER2 extracellular and transmembrane domains, has demonstrated safety and efficacy in preclinical mouse models, as well as in phase I clinical trials for advanced breast cancer patients with HER2 overexpression. This vaccine is known to be safe, effective, and capable of inducing T-cell immunity. In this review, we discuss the current progress in preclinical and clinical investigations, as well as the future potential of Alphaviruses for oncolytic virotherapy.

Published
2023
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12. The Specificity of Epizootic and Epidemiological Processes in Natural Foci of Hemorrhagic Fever with Renal Syndrome and Tick-Borne Encephalitis in Russia, as the Basis for the Prospects of Creating a Combined Vaccine for the Prevention of These Infections

Author

Evgeniy Tkachenko, Alexandra Balkina, Dmitriy Trankvilevsky, Nadezda Kolyasnikova, Rostislav Teodorovich, Mikhail Vorovich, Yulia Popova, Svetlana Kurashova, Maria Egorova, Alla Belyakova, Petr Tkachenko, Aydar Ishmukhametov, and Tamara Dzagurova

Subjects
hantavirus, hemorrhagic fever with renal syndrome, tick-borne encephalitis, reservoir hosts, natural foci, incidence rate, Microbiology, QR1-502
Abstract

Hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) are the most common viral diseases in Russia. HFRS is caused by six different types of hantaviruses: Hantaan, Amur, Seoul, Puumala, Kurkino, and Sochi, which are transmitted to humans through small mammals of the Muridae and Cricetidae families. TBE is caused by viruses belonging to five different phylogenetic subtypes. The similarities in the ecology of HFRS and TBE pathogens is presented here. Hantavirus-infected small mammals can transmit the virus to uninfected animals, and ticks can also transmit hantavirus to other ticks and mammals. Hantavirus transmission from ticks to humans is possible only hypothetically based on indirect data. Over the past 23 years, 164,582 cases of HFRS (4.9 per 105 people) and 71,579 cases of TBE (2.5 per 105 people) were registered in Russia. The mortality rate was 0.4% (668 cases) in HFRS and 1.6% deaths (1136 cases) in TBE. There were 4030 HFRS (2.5%) and 9414 TBE (13%) cases in children under 14 years old. HFRS and TBE cases were registered in 42 out of 85 Russian regions; in 18—only HFRS, in 13—only TBE, and 12 had no reported cases. The prospects of applying a combined vaccine for HFRS and TBE prevention are shown in this paper.

Published
2024
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13. Prevalence and Clinical Impact of Viral and Bacterial Coinfections in Hospitalized Children and Adolescents Aged under 18 Years with COVID-19 during the Omicron Wave in Russia

Author

Alexander S. Yakovlev, Vladislav V. Afanasev, Svetlana I. Alekseenko, Ilmira K. Belyaletdinova, Ludmila N. Isankina, Irina A. Gryaznova, Anatoly V. Skalny, Liubov I. Kozlovskaya, Aydar A. Ishmukhametov, and Galina G. Karganova

Subjects
COVID-19, SARS-CoV-2, influenza virus, bacterial pathogens, coinfections, respiratory viruses, Microbiology, QR1-502
Abstract

The COVID-19 pandemic has altered respiratory infection patterns in pediatric populations. The emergence of the SARS-CoV-2 Omicron variant and relaxation of public health measures have increased the likelihood of coinfections. Previous studies show conflicting results regarding the impact of viral and bacterial coinfections with SARS-CoV-2 on severity of pediatric disease. This study investigated the prevalence and clinical impact of coinfections among children hospitalized with COVID-19 during the Omicron wave. A retrospective analysis was conducted on 574 hospitalized patients aged under 18 years in Russia, from January 2022 to March 2023. Samples from patients were tested for SARS-CoV-2 and other respiratory pathogens using qRT-PCR, bacterial culture tests and mass spectrometry, and ELISA. Approximately one-third of COVID-19 cases had coinfections, with viral and bacterial coinfections occurring at similar rates. Adenovirus and Staphylococcus aureus were the most common viral and bacterial coinfections, respectively. Viral coinfections were associated with higher fevers and increased bronchitis, while bacterial coinfections correlated with longer duration of illness and higher pneumonia rates. Non-SARS-CoV-2 respiratory viruses were linked to more severe lower respiratory tract complications than SARS-CoV-2 monoinfection. These findings suggest that during the Omicron wave, seasonal respiratory viruses may have posed a greater threat to children’s health than SARS-CoV-2.

Published
2024
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17. An Integrative Approach to the Study of Cognitive Abilities in a Non-Human Primate Model in a Virology Laboratory Environment

Author

Anastasia Rogova, Anna Kalyanova, Yulia Rogova, Maria Fedina, Alexandra Siniugina, Aydar Ishmukhametov, and Galina Karganova

Subjects
behavior, cognitive tests, cognitive function, training techniques, positive reinforcement training, non-human primates, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Non-human primates, due to their similarities in immune response to humans, are the preferred model for studying infectious processes and any associated cognitive impairments. Behavioral tests are indispensable for investigating pathogenesis in neuroinfections, especially those that do not manifest with noticeable clinical symptoms, as well as in the transition to a chronic form of the disease. Modeling viral infection requires specialized experimental conditions. Our work describes techniques for investigating mnemonic functions, tiredness, attentional focus, quick-wittedness, and basic behavioral responses in primates under the assumed conditions for infections with viruses that do not have an airborne route of transmission. It also outlines approaches to the training and selection of primates for virological research, as well as analyzing gender differences in learning abilities, the impact of housing conditions on the results, and the correlation between training success and behavioral test scores. These methods will allow a more detailed study of non-human primates as a model for researching cognitive and behavioral impairments under infectious and immune stress, as well as the design of less energy-intensive experiments for evaluating the efficacy and safety of therapeutic and prophylactic strategies at early stages of infection.

Published
2024
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18. Susceptibility of various cell lines to the Chikungunya virus and method selection for commercial-scale production of viral material

Author

K. V. Kaa, G. M. Ignatyev, A. A. Sinyugina, and A. A. Ishmukhametov

Subjects
cell line, chikungunya virus, vaccine, multiplicity of infection, virus infectious titre, selection of the minimum infective dose, vero, c6/36, mrc-5, fek, 4647, Biotechnology, TP248.13-248.65, Medicine
Abstract

An increase in cases of chikungunya fever is reported in the Caribbean, Central and South America, and Southeast Asia. As there is no specific treatment for this disease and the only available treatment is symptomatic, it is very relevant to develop vaccines against chikungunya fever. To develop an inactivated whole-virion vaccine against the disease, it is important to choose a susceptible cell culture that both provides high virus yields and is used for vaccine production.The aim of the study was to evaluate the susceptibility of multiple cell lines to Chikungunya virus infection and to select the monolayer culture method with the highest virus accumulation and yield.Materials and methods. The study used the CHIKV_Nic strain of the Chikungunya virus and cell lines C6/36 (for virus titration), CEF, MRC-5, Vero, and 4647. While choosing the culture method, the authors used culture flasks, a cell factory, and roller bottles. The authors determined the susceptibility of the cell lines to viral infection by the degree of accumulation of the infectious agent in the culture fluid. The results of virus titration were calculated on day 5 on the basis of a pronounced viral cytopathic effect.Results. The Vero and 4647 cell lines demonstrated the highest susceptibility to infection and virus concentrations in the culture fluid. The СEF and MRC-5 cell lines accumulated the virus at lower concentrations. The maximum virus titres (7.10–7.75 log10 TCID50/mL) were observed in the culture fluid 48 h after infection. The optimal multiplicity of infection (MOI) ranged between 0.001 and 0.0001 MOI/cell. At 0.0001 MOI/cell, the virus accumulated in the Vero cells cultured in roller bottles on day 2, with the maximum virus titre being 8.6±0.2 log10 TCID50/mL.Conclusions. Vero cells meet the safety and stability requirements set for the production of chikungunya vaccines. The study determined the minimum MOI of the Chikungunya virus for cell culture. The roller bottle culture method provides the highest cell culture yield and the highest titre of the virus in the culture fluid.

Published
2023
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19. Changes within the central stalk of E. coli F1Fo ATP synthase observed after addition of ATP

Author

Meghna Sobti, Yi C. Zeng, James L. Walshe, Simon H. J. Brown, Robert Ishmukhametov, and Alastair G. Stewart

Subjects
Biology (General), QH301-705.5
Abstract

Cryo-EM structures of E. coli F1Fo ATP synthase highlight the role of the inhibitory ε subunit in regulating the torsional movement of the central stalk within the Fo motor and central stalk flexibility in coupling the F1 and Fo motors.

Published
2023
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22. Properties and Activity of Peptide Derivatives of ACE2 Cellular Receptor and Their Interaction with SARS-CoV-2 S Protein Receptor-Binding Domain

Author

Sidorova, M. V., Bibilashvili, R. S., Avdeev, D. V., Kozhokar, U. S., Palkeeva, M. E., Ovchinnikov, M. V., Molokoedov, A. S., Shirokov, D. A., Semyonova, A. V., Uvarova, V. I., Kulyaev, P. O., Khvatov, E. V., Ignatova, A. A., Feofanov, A. V., Osolodkin, D. I., Porozov, Yu. B., Kozlovskaya, L. I., Ishmukhametov, A. A., Parfyonova, Ye. V., and Egorov, A. M.

Published
2022
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23. Comprehensive Elucidation of the Role of L and 2A Security Proteins on Cell Death during EMCV Infection

Author

Yury Ivin, Anna Butusova, Ekaterina Gladneva, Anatoly Gmyl, and Aydar Ishmukhametov

Subjects
EMCV, leader protein, 2A protein, security protein, apoptosis, viral infection, Microbiology, QR1-502
Abstract

The EMCV L and 2A proteins are virulence factors that counteract host cell defense mechanisms. Both L and 2A exhibit antiapoptotic properties, but the available data were obtained in different cell lines and under incomparable conditions. This study is aimed at checking the role of these proteins in the choice of cell death type in three different cell lines using three mutants of EMCV lacking functional L, 2A, and both proteins together. We have found that both L and 2A are non-essential for viral replication in HeLa, BHK, and RD cell lines, as evidenced by the viability of the virus in the absence of both functional proteins. L-deficient infection led to the apoptotic death of HeLa and RD cells, and the necrotic death of BHK cells. 2A-deficient infection induced apoptosis in BHK and RD cells. Infection of HeLa cells with the 2A-deficient mutant was finalized with exclusive caspase-dependent death with membrane permeabilization, morphologically similar to pyroptosis. We also demonstrated that inactivation of both proteins, along with caspase inhibition, delayed cell death progression. The results obtained demonstrate that proteins L and 2A play a critical role in choosing the path of cell death during infection, but the result of their influence depends on the properties of the host cells.

Published
2024
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24. ARCHAIN: A Novel Blockchain Based Archival System

Author

Galiev, Albert, Ishmukhametov, Shamil, Latypov, Rustam, Prokopyev, Nikolai, Stolov, Evgeni, and Vlasov, Ilya

Subjects
Computer Science - Cryptography and Security
Abstract

In this paper, we propose a novel archival system called ARCHAIN, developed for the State archive-keeping committee of the Republic of Tatarstan (Russia). The blockchain is the primary part of the system, which stores transactions (facts of transfer of documents to the archive) in a protected form.

Published
2019

25. Electronic Tools for Development of Small and Medium Enterprise

Author

Gaisina, Radmila R., Ishmukhametov, Edgar M., Khisaeva, Aliya I., Shaykhutdinova, Gulnara F., Pisello, Anna Laura, Editorial Board Member, Hawkes, Dean, Editorial Board Member, Bougdah, Hocine, Editorial Board Member, Rosso, Federica, Editorial Board Member, Abdalla, Hassan, Editorial Board Member, Boemi, Sofia-Natalia, Editorial Board Member, Mohareb, Nabil, Editorial Board Member, Mesbah Elkaffas, Saleh, Editorial Board Member, Bozonnet, Emmanuel, Editorial Board Member, Pignatta, Gloria, Editorial Board Member, Mahgoub, Yasser, Editorial Board Member, De Bonis, Luciano, Editorial Board Member, Kostopoulou, Stella, Editorial Board Member, Pradhan, Biswajeet, Editorial Board Member, Abdul Mannan, Md., Editorial Board Member, Alalouch, Chaham, Editorial Board Member, O. Gawad, Iman, Editorial Board Member, Nayyar, Anand, Editorial Board Member, Amer, Mourad, Series Editor, and Popkova, Elena G., editor

Published
2022
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26. Immunogenicity and protectivity of intranasally delivered vector-based heterologous prime-boost COVID-19 vaccine Sputnik V in mice and non-human primates

Author

Amir I. Tukhvatulin, Ilya V. Gordeychuk, Inna V. Dolzhikova, Alina S. Dzharullaeva, Marina E. Krasina, Ekaterina O. Bayurova, Daria M. Grousova, Anna V. Kovyrshina, Alla S. Kondrashova, Daria V. Avdoshina, Stanislav A. Gulyaev, Tatiana V. Gulyaeva, Andrey V. Moroz, Viktoria V. Illarionova, Ilya D. Zorkov, Anna A. Iliukhina, Artem Y. Shelkov, Andrei G. Botikov, Alina S. Erokhova, Dmitry V. Shcheblyakov, Ilias B. Esmagambetov, Olga V. Zubkova, Elisaveta A. Tokarskaya, Daria M. Savina, Yulia R. Vereveyko, Anastasiya S. Ungur, Boris S. Naroditsky, Aydar A. Ishmukhametov, Denis Y. Logunov, and Alexander L. Gintsburg

Subjects
Sputnik V, Gam-COVID-Vac, intranasal vaccine, SARS-CoV-2, COVID-19, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Although unprecedented efforts aiming to stop the COVID-19 pandemic have been made over the past two years, SARSCoV-2 virus still continues to cause intolerable health and economical losses. Vaccines are considered the most effective way to prevent infectious diseases, which has been reaffirmed for COVID-19. However, in the context of the continuing virus spread because of insufficient vaccination coverage and emergence of new variants of concern, there is a high demand for vaccination strategy amendment. The ability to elicit protective immunity at the entry gates of infection provided by mucosal vaccination is key to block virus infection and transmission. Therefore, these mucosal vaccines are believed to be a “silver bullet” that could bring the pandemic to an end. Here, we demonstrate that the intranasally delivered Gam-COVID-Vac (Sputnik V) vaccine induced a robust (no less than 180 days) systemic and local immune response in mice. High immunogenic properties of the vaccine were verified in non-human primates (common marmosets) by marked IgG and neutralizing antibody (NtAb) production in blood serum, antigen-specific Tcell proliferation and cytokine release of peripheral blood mononuclear cells accompanied by formation of IgA antibodies in the nasal mucosa. We also demonstrate that Sputnik V vaccine can provide sterilizing immunity in K18-hACE2 transgenic mice exposed to experimental lethal SARS-CoV-2 infection protecting them against severe lung immunopathology and mortality. We believe that intranasal Sputnik V vaccine is a promising novel needle-free mucosal vaccine candidate for primary immunization as well as for revaccination and is worth further clinical investigation.

Published
2022
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27. Vaccine-associated paralytic poliomyelitis in a child: fast transformation from Sabin-like virus to vaccine-derived poliovirus triggered an epidemiological response in two countries of the European region

Author

Olga E. Ivanova, Liubov I. Kozlovskaya, Tatiana P. Eremeeva, Armen K. Shakaryan, Alexander P. Ivanov, Olga Y. Baykova, Alexander Y. Krasota, Elena Y. Shustova, Aida N. Mustafina, Nadezhda S. Morozova, Makhtob S. Bobokhonova, Sergei E. Deshevoi, and Aidar A. Ishmukhametov

Subjects
AFP, VAPP, Genome analysis, Epidemiological surveillance, Immunization, VDPV, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: The detection of a vaccine-derived poliovirus (VDPV) requires an epidemiological assessment and response. Using repeated stool sampling from a child who is immunocompetent and was vaccinated against poliomyelitis with acute flaccid paralysis, a case of an extremely rapid evolution of Sabin-like poliovirus (PV) type 3 was traced in the child's body. Methods: The case was independently identified in two countries—Tajikistan and Russia. Stool samples for the study were also independently collected in two countries on different days from the onset of paralysis. Virological, serological, and molecular methods; full genome Sanger; and high-throughput sequencing were performed to characterize isolates. Results: PV isolates from samples collected on days 2, 3, and 14 contained eight, seven, and seven mutations in the VP1-coding region, respectively, and were classified as Sabin-like PV type 3. The isolates from samples collected on days 15 and 18 had 11 mutations and were classified as vaccine-derived PVs, which required an epidemiological response in the two countries. Conclusion: The results indicate the need to continue acute flaccid paralysis surveillance, maintain high vaccination coverage, and develop and introduce new effective, genetically stable PV vaccines.

Published
2022
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28. Application of Ion Exchange Chromatography in the Development of Technology to Obtain Inactivated Poliovirus Vaccine

Author

A. N. Piniaeva, A. A. Kovpak, Y. Y. Ivin, S. H. Sandzhieva, A. A. Shishova, I. O. Tсelykh, V. E. Vasilenko, K. V. Kaa, Zh. H. Mazhed, Yu. Kh. Khapchaev, A. A. Siniugina, and A. A. Ishmukhametov

Subjects
инактивированная вакцина против полиомиелита (ипв), полиомиелит, штаммы сэбина, ионообменная хроматография, клеточная линия vero, остаточная клеточная днк, Epistemology. Theory of knowledge, BD143-237
Abstract

Relevance. The production and quality control of any drugs are strictly regulated. In the case of antiviral vaccines, the requirements for their safety and protective activity are getting tougher every year. Vaccine manufacturers face three tasks: ensuring high immunogenicity, safety and availability of the drug. During the development and production of immunobiological drugs, manufacturers must demonstrate sufficient purification from technological impurities to ensure the purity of the drug. Technological impurities directly depend on the technological process and the expression systems used. The Vero cell line has been widely used in the production of various antiviral vaccines for many decades. Thus, the improvement of technological processes for the purification of vaccine preparations from proteins and DNA of Vero cells is still matter of current interest.Aims. Selection of resins and reagents for ion exchange chromatography to reduce the amount of technological impurities in the inactivated polio vaccine production.Materials and Methods. To obtain viral suspensions, producer cultures were infected with poliovirus type 1 (Sabin strain LSc 2ab), type 2 (Sabin strain P712 Ch 2ab), and type 3 (Sabin strain Leon 12a1b). Multiplicity of infection was 0.02 ± 0.01 TCD50/cell. To evaluate the efficiency of ion-exchange chromatography we determined the degree of purification of fractions from ballast proteins, the degree of purification of fractions from residual cellular DNA, and the degree of extraction of the target antigen using specific formulas.Results and discussion. More than 80 experiments have been performed to purify type 1, type 2, and type 3 poliovirus concentrates using various sorbents. In quality control of purified concentrates of type 1, type 2 and type 3 polioviruses, in addition to analysis for total protein, an analysis was performed for the presence of Vero cell proteins.Conclusion. The use of the proposed modifications of purification of concentrates of Sabin strains of poliovirus types 1, 2 and 3 using ion exchange chromatography allows to obtain inactivated viral products that meet the requirements of WHO and the European Pharmacopoeia both in biochemical parameters (the content of host-cell DNA and the content of ballast proteins, including host-cell proteins) and specific activity (D-antigen content). Furthermore, additional purification of vaccines using ion exchange chromatography allows to reduce the content of residual cellular DNA to almost zero, which makes the inactivated polio vaccine the most attractive for its inclusion in various combined vaccines.

Published
2022
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29. Immune response evaluation in the guinea pigs after immunization with the experimental Puumala virus vaccine

Author

S. S. Kurashova, M. V. Balovneva, A. A. Ishmukhametov, R. D. Teodorovich, Yu. V. Popova, E. A. Tkachenko, and T. K. Dzagurova

Subjects
hemorrhagic fever with renal syndrome, puumala virus, hantavirus vaccine, vaccination schedule, neutralizing antibodies, immune response, Infectious and parasitic diseases, RC109-216
Abstract

In the Russian Federation, the vaccine against hemorrhagic fever with renal syndrome is at the stage of preclinical and clinical trials. The aim of the study was to analyze an effect of vaccine schedule on neutralizing antibodies (nAB) dynamics in guinea pig models applied with experimental Puumala virus based hantavirus vaccine (HV). Quantitative evaluation of neutralizing antibodies was presented as antibody titer geometric mean expressed in binary logarithms (log2) by the 50% reduction of focus-forming units (FRNT50) in Vero cell in the focus reduction neutralization test. The HV dual inoculation to guinea pigs was carried out in 14 day intervals, booster injection was applied on day 182 after the onset, in the thigh muscle tissue by using 0.3 ml undiluted (HV-u/d) and in the 1/10 dilution (HV-1/10). nAB titer on day 14 after the first HV-u/d and HV-1/10 injection was measured to be at titer of 5.50.3 and 4.80.3, respectively. After the second injection, the nAB peak was as high as 90.2 on day 42 after the first HV-u/f injection, and 6.50.2 on day 14 after the HV-1/10 injection. nAB decreased down to 6.20.3 and 50.3, respectively, on day 364 after the first injection. The booster HV-u/d and HV-1/10 injection induced increase in nAB up to 9.50.3 and 6.50.3, respectively. After the booster injection, it induced significantly higher nAB observed on day 238 after the first HV-u/d injection and delayed up to the 294 day for the HV-1/10. The results of the study indicated the early formation of the immune response, long-term nAB persistence and significantly enhanced immune response after the booster injection on day 182, which indicated a potential for the booster injection a year later. The immunological efficacy and protective activity of the vaccine schedule may be finally assessed according to the results of clinical trials.

Published
2022
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32. Urine excreted antibodies significance in the hemorrhagic fever with renal syndrome specific diagnosis

Author

T. K. Dzagurova, R. T. Murzabaeva, F. G. Kutluguzhina, V. G. Morozov, E. V. Volnyh, S. S. Kurashova, M. V. Balovneva, P. E. Tkachenko, A. A. Ishmukhametov, A. V. Belyakova, and E. A. Tkachenko

Subjects
hemorrhagic fever with renal syndrome, hantaviruses, indirect fluorescent antibody assay, early specific diagnosis, Infectious and parasitic diseases, RC109-216
Abstract

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is an acute viral zoonosis. Being widespread in Eurasia, it holds a leading place in Russia among natural focal human diseases. The vast majority of HFRS cases in Russia, about 98%, are associated with Puumala virus. The disease is characterized by a wide range of clinical manifestations. Early specific diagnostics appears to be of a great importance for starting timely pathogenic therapy. The aim of the study was to clarify the diagnostic value of detecting hantavirus antibodies in the HFRS suspected patient urine. Materials and methods. Blood sera and urine samples from 68 patients at the Infectious Diseases Hospital in the city of Ufa, obtained with a 2-day interval, as well as urine and blood serum samples from 15 convalescents 1, 2, 3 and 6 months after disease onset were examined for hantavirus antibodies. 53 blood sera and urine samples from patients residing in Moscow, Moscow and Samara regions collected at different time points during the disease course were investigated in parallel. Antibodies were detected by the indirect immunofluorescence method. Results. On day 3, 4, 5 and 6 of disease, while specific antibodies were detected in the blood serum, antibodies in the urine were found in 85.7%, 89.4%, 93.1% and 100% of patients, respectively. The peak quantity of antibodies was excreted in the urine from days 5 to 11, which corresponds to the oliguric stage of the disease. In the convalescent period, antibodies were still detected in urine 1, 2 and 3 months afterwards in 86.7%, 46% and 20% of cases, respectively, but not detected 6 months later, which probably reflects the process of long-term restoration of the kidneys function. A moderate positive correlation between specific antibodies in serum and urine was observed only in the oliguric period of the disease. Conclusions. Detection of hantavirus antibodies simultaneously in blood serum and urine of febrile patients instead of paired blood sera allows to conduct HFRS diagnostics within the very first days of hospitalization and prevent severe complications due to timely pathogenic therapy.

Published
2022
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33. Phenotypic assessment of antiviral activity for spiro‐annulated oxepanes and azepenes

Author

Osolodkin, Dmitry I., primary, Kozlovskaya, Liubov I., additional, Iusupov, Ildar R., additional, Kurkin, Alexander V., additional, Shustova, Elena Y., additional, Orlov, Alexey A., additional, Khvatov, Evgeny V., additional, Mutnykh, Elena S., additional, Kurashova, Svetlana S., additional, Vetrova, Anna N., additional, Yatsenko, Darya O., additional, Goryashchenko, Alexander S., additional, Ivanov, Vladimir N., additional, Lukyanenko, Evgeny R., additional, Karpova, Evgenia V., additional, Stepanova, Daria A., additional, Volok, Viktor P., additional, Sotskova, Svetlana E., additional, Dzagurova, Tamara K., additional, Karganova, Galina G., additional, Lukashev, Alexander N., additional, and Ishmukhametov, Aydar A., additional

Published
2024
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35. Inapparent Tick-Borne Orthoflavivirus Infection in Macaca fascicularis: A Model for Antiviral Drug and Vaccine Research

Author

Victoria Illarionova, Anastasia Rogova, Ksenia Tuchynskaya, Viktor Volok, Yulia Rogova, Victoria Baryshnikova, Yuriy Turchenko, Alexander Litov, Anna Kalyanova, Alexandra Siniugina, Aydar Ishmukhametov, and Galina Karganova

Subjects
orthoflaviviruses, tick-borne encephalitis virus, Powassan virus, TBE vaccine, cognitive impairment, antibody spectrum, Medicine
Abstract

Tick-borne encephalitis virus (TBEV) and Powassan virus (POWV) are neurotropic tick-borne orthoflaviviruses. They cause mostly asymptomatic infections in hosts, but severe forms with CNS involvement can occur. Studying the early stages of viral infections in humans is challenging, and appropriate animal models are essential for understanding the factors determining the disease severity and for developing emergency prophylaxis and treatment options. In this work, we assessed the model of the early stages of TBEV and POWV mono- and co-infections in Macaca fascicularis. Serological, biochemical, and virological parameters were investigated to describe the infection, including its impact on animal behavior. Viremia, neutralizing antibody dynamics, and viral load in organs were chosen as the main parameters distinguishing early-stage orthoflavivirus infection. Levels of IFNα, monocyte count, and cognitive test scores were proposed as additional informative indicators. An assessment of a tick-borne encephalitis vaccine using this model showed that it provided partial protection against POWV infection in Macaca fascicularis without signs of antibody-dependent enhancement of infection.

Published
2023
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36. Production and Integration of the ATLAS Insertable B-Layer

Author

Abbott, B., Albert, J., Alberti, F., Alex, M., Alimonti, G., Alkire, S., Allport, P., Altenheiner, S., Ancu, L., Anderssen, E., Andreani, A., Andreazza, A., Axen, B., Arguin, J., Backhaus, M., Balbi, G., Ballansat, J., Barbero, M., Barbier, G., Bassalat, A., Bates, R., Baudin, P., Battaglia, M., Beau, T., Beccherle, R., Bell, A., Benoit, M., Bermgan, A., Bertsche, C., Bertsche, D., de Mendizabal, J. Bilbao, Bindi, F., Bomben, M., Borri, M., Bortolin, C., Bousson, N., Boyd, R., Breugnon, P., Bruni, G., Brossamer, J., Bruschi, M., Buchholz, P., Budun, E., Buttar, C., Cadoux, F., Calderini, G., Caminada, L., Capeans, M., Carney, R., Casse, G., Catinaccio, A., Cavalli-Sforza, M., Červ, M., Cervelli, A., Chau, C., Chauveau, J., Chen, S., Chu, M., Ciapetti, M., Cindro, V., Citterio, M., Clark, A., Cobal, M., Coelli, S., Collot, J., Crespo-Lopez, O., Betta, G. Dalla, Daly, C., D'Amen, G., Dann, N., Dao, V., Darbo, G., DaVia, C., David, P., Debieux, S., Delebecque, P., De Lorenzi, F., de Oliveira, R., Dette, K., Dietsche, W., Di Girolamo, B., Dinu, N., Dittus, F., Diyakov, D., Djama, F., Dobos, D., Dondero, P., Doonan, K., Dopke, J., Dorholt, O., Dube, S., Dzahini, D., Egorov, K., Ehrmann, O., Einsweiler, K., Elles, S., Elsing, M., Eraud, L., Ereditato, A., Eyring, A., Falchieri, D., Falou, A., Fausten, C., Favareto, A., Favre, Y., Feigl, S., Perez, S. Fernandez, Ferrere, D., Fleury, J., Flick, T., Forshaw, D., Fougeron, D., Franconi, L., Gabrielli, A., Gaglione, R., Gallrapp, C., Gan, K., Garcia-Sciveres, M., Gariano, G., Gastaldi, T., Gavrilenko, I., Gaudiello, A., Geffroy, N., Gemme, C., Gensolen, F., George, M., Ghislain, P., Giangiacomi, N., Gibson, S., Giordani, M., Giugni, D., Gjersdal, H., Glitza, K., Gnani, D., Godlewski, J., Gonella, L., Gonzalez-Sevilla, S., Gorelov, I., Gorišek, A., Gössling, C., Grancagnolo, S., Gray, H., Gregor, I., Grenier, P., Grinstein, S., Gris, A., Gromov, V., Grondin, D., Grosse-Knetter, J., Guescini, F., Guido, E., Gutierrez, P., Hallewell, G., Hartman, N., Hauck, S., Hasi, J., Hasib, A., Hegner, F., Heidbrink, S., Heim, T., Heinemann, B., Hemperek, T., Hessey, N., Hetmánek, M., Hinman, R., Hoeferkamp, M., Holmes, T., Hostachy, J., Hsu, S., Hügging, F., Husi, C., Iacobucci, G., Ibragimov, I., Idarraga, J., Ikegami, Y., Ince, T., Ishmukhametov, R., Izen, J. M., Janoška, Z., Janssen, J., Jansen, L., Jeanty, L., Jensen, F., Jentzsch, J., Jezequel, S., Joseph, J., Kagan, H., Kagan, M., Karagounis, M., Kass, R., Kastanas, A., Kenney, C., Kersten, S., Kind, P., Klein, M., Klingenberg, R., Kluit, R., Kocian, M., Koffeman, E., Korchak, O., Korolkov, I., Kostyukhina-Visoven, I., Kovalenko, S., Kretz, M., Krieger, N., Krüger, H., Kruth, A., Kugel, A., Kuykendall, W., La Rosa, A., Lai, C., Lantzsch, K., Lapoire, C., Laporte, D., Lari, T., Latorre, S., Leyton, M., Lindquist, B., Looper, K., Lopez, I., Lounis, A., Lu, Y., Lubatti, H., Maeland, S., Maier, A., Mallik, U., Manca, F., Mandelli, B., Mandić, I., Marchand, D., Marchiori, G., Marx, M., Massol, N., Mättig, P., Mayer, J., Goldrick, G. Mc, Mekkaoui, A., Menouni, M., Menu, J., Meroni, C., Mesa, J., Michal, S., Miglioranzi, S., Mikuž, M., Miucci, A., Mochizuki, K., Monti, M., Moore, J., Morettini, P., Morley, A., Moss, J., Muenstermann, D., Murray, P., Nakamura, K., Nellist, C., Nelson, D., Nessi, M., Nisius, R., Nordberg, M., Nuiry, F., Obermann, T., Ockenfels, W., Oide, H., Oriunno, M., Ould-Saada, F., Padilla, C., Pangaud, P., Parker, S., Pelleriti, G., Pernegger, H., Piacquadio, G., Picazio, A., Pohl, D., Polini, A., Pons, X., Popule, J., Bueso, X. Portell, Potamianos, K., Povoli, M., Puldon, D., Pylypchenko, Y., Quadt, A., Quayle, B., Rarbi, F., Ragusa, F., Rambure, T., Richards, E., Riegel, C., Ristic, B., Rivière, F., Rizatdinova, F., Røhne, O., Rossi, C., Rossi, L., Rovani, A., Rozanov, A., Rubinskiy, I., Rudolph, M., Rummler, A., Ruscino, E., Sabatini, F., Salek, D., Salzburger, A., Sandaker, H., Sannino, M., Sanny, B., Scanlon, T., Schipper, J., Schmidt, U., Schneider, B., Schorlemmer, A., Schroer, N., Schwemling, P., Sciuccati, A., Seidel, S., Seiden, A., Šícho, P., Skubic, P., Sloboda, M., Smith, D., Smith, M., Sood, A., Spencer, E., Stramaglia, M., Strauss, M., Stucci, S., Stugu, B., Stupak, J., Styles, N., Su, D., Takubo, Y., Tassan, J., Teng, P., Teixeira, A., Terzo, S., Therry, X., Todorov, T., Tomášek, M., Toms, K., Travaglini, R., Trischuk, W., Troncon, C., Troska, G., Tsiskaridze, S., Tsurin, I., Tsybychev, D., Unno, Y., Vacavant, L., Verlaat, B., Vigeolas, E., Vogt, M., Vrba, V., Vuillermet, R., Wagner, W., Walkowiak, W., Wang, R., Watts, S., Weber, M., Weingarten, J., Welch, S., Wenig, S., Wensing, M., Wermes, N., Wittig, T., Wittgen, M., Yildizkaya, T., Yang, Y., Yao, W., Yi, Y., Zaman, A., Zaidan, R., Zeitnitz, C., Ziolkowski, M., Zivkovic, V., Zoccoli, A., and Zwalinski, L.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

During the shutdown of the CERN Large Hadron Collider in 2013-2014, an additional pixel layer was installed between the existing Pixel detector of the ATLAS experiment and a new, smaller radius beam pipe. The motivation for this new pixel layer, the Insertable B-Layer (IBL), was to maintain or improve the robustness and performance of the ATLAS tracking system, given the higher instantaneous and integrated luminosities realised following the shutdown. Because of the extreme radiation and collision rate environment, several new radiation-tolerant sensor and electronic technologies were utilised for this layer. This paper reports on the IBL construction and integration prior to its operation in the ATLAS detector., Comment: 90 pages in total. Author list: ATLAS IBL Collaboration, starting page 2. 69 figures, 20 tables. Published in Journal of Instrumentation. All figures available at: https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PLOTS/PIX-2018-001

Published
2018
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37. Vaccine-associated paralytic poliomyelitis in a child: fast transformation from Sabin-like virus to vaccine-derived poliovirus triggered an epidemiological response in two countries of the European region

Author

Ivanova, Olga E., Kozlovskaya, Liubov I., Eremeeva, Tatiana P., Shakaryan, Armen K., Ivanov, Alexander P., Baykova, Olga Y., Krasota, Alexander Y., Shustova, Elena Y., Mustafina, Aida N., Morozova, Nadezhda S., Bobokhonova, Makhtob S., Deshevoi, Sergei E., and Ishmukhametov, Aidar A.

Published
2022
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40. SARS-CoV-2 infection in children in Moscow in 2020: clinical features and impact on circulation of other respiratory viruses

Author

Alexander S. Yakovlev, Ilmira K. Belyaletdinova, Lyudmila N. Mazankova, Elmira R. Samitova, Ismail M. Osmanov, Nataly V. Gavelya, Viktor P. Volok, Ekaterina S. Kolpakova, Anna A. Shishova, Natalia A. Dracheva, Liubov I. Kozlovskaya, Galina G. Karganova, and Aydar A. Ishmukhametov

Subjects
COVID-19, Molecular diagnostics, Respiratory viruses, SARS-CoV-2, Obesity, Children, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: This study aimed to estimate the impact of the COVID-19 pandemic on the circulation of non-SARS-CoV-2 respiratory viruses and the clinical characteristics of COVID-19 in hospitalized children. Methods: A total of 226 and 864 children admitted to the Children's City Clinical Hospital with acute respiratory infection in September to November of 2018 and 2020 in Moscow were tested for respiratory viruses using multiplex polymerase chain reaction (PCR) and Mycoplasma pneumoniae/Chlamydia pneumoniae using enzyme-linked immunosorbent assay. Results: The detection rate of non-SARS-CoV-2 viruses in 2020 was lower than in 2018, 16.9% versus 37.6%. An increase in the median age of children with respiratory viruses was observed during the pandemic (3 years vs 1 year). There was no significant difference in the frequency of intensive care unit (ICU) admission in children with SARS-CoV-2 and other respiratory virus infections (2.7% vs 2.9%). SARS-CoV-2 and human rhinoviruses, human metapneumoviruses, and human adenoviruses showed significantly lower than expected co-detection rates during co-circulation. An increase in body mass index (BMI) or bacterial coinfection leads to an increased risk of ICU admission and a longer duration of COVID-19 in children. Conclusions: The COVID-19 pandemic led to significant changes in the epidemiological characteristics of non-SARS-CoV-2 respiratory viruses during the autumn peak of the 2020 pandemic, compared with the same period in 2018.

Published
2022
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41. Erratum to: Search for single top-quark production via flavour-changing neutral currents at 8 TeV with the ATLAS detector

Author

G. Aad, B. Abbott, J. Abdallah, O. Abdinov, R. Aben, M. Abolins, O. S. AbouZeid, H. Abramowicz, H. Abreu, R. Abreu, Y. Abulaiti, B. S. Acharya, L. Adamczyk, D. L. Adams, J. Adelman, S. Adomeit, T. Adye, A. A. Affolder, T. Agatonovic-Jovin, J. Agricola, J. A. Aguilar-Saavedra, S. P. Ahlen, F. Ahmadov, G. Aielli, H. Akerstedt, T. P. A. Åkesson, A. V. Akimov, G. L. Alberghi, J. Albert, S. Albrand, M. J. Alconada Verzini, M. Aleksa, I. N. Aleksandrov, C. Alexa, G. Alexander, T. Alexopoulos, M. Alhroob, G. Alimonti, L. Alio, J. Alison, S. P. Alkire, B. M. M. Allbrooke, P. P. Allport, A. Aloisio, A. Alonso, F. Alonso, C. Alpigiani, A. Altheimer, B. Alvarez Gonzalez, D. Álvarez Piqueras, M. G. Alviggi, B. T. Amadio, K. Amako, Y. Amaral Coutinho, C. Amelung, D. Amidei, S. P. Amor Dos Santos, A. Amorim, S. Amoroso, N. Amram, G. Amundsen, C. Anastopoulos, L. S. Ancu, N. Andari, T. Andeen, C. F. Anders, G. Anders, J. K. Anders, K. J. Anderson, A. Andreazza, V. Andrei, S. Angelidakis, I. Angelozzi, P. Anger, A. Angerami, F. Anghinolfi, A. V. Anisenkov, N. Anjos, A. Annovi, M. Antonelli, A. Antonov, J. Antos, F. Anulli, M. Aoki, L. Aperio Bella, G. Arabidze, Y. Arai, J. P. Araque, A. T. H. Arce, F. A. Arduh, J-F. Arguin, S. Argyropoulos, M. Arik, A. J. Armbruster, O. Arnaez, V. Arnal, H. Arnold, M. Arratia, O. Arslan, A. Artamonov, G. Artoni, S. Asai, N. Asbah, A. Ashkenazi, B. Åsman, L. Asquith, K. Assamagan, R. Astalos, M. Atkinson, N. B. Atlay, K. Augsten, M. Aurousseau, G. Avolio, B. Axen, M. K. Ayoub, G. Azuelos, M. A. Baak, A. E. Baas, M. J. Baca, C. Bacci, H. Bachacou, K. Bachas, M. Backes, M. Backhaus, P. Bagiacchi, P. Bagnaia, Y. Bai, T. Bain, J. T. Baines, O. K. Baker, E. M. Baldin, P. Balek, T. Balestri, F. Balli, E. Banas, Sw. Banerjee, A. A. E. Bannoura, H. S. Bansil, L. Barak, E. L. Barberio, D. Barberis, M. Barbero, T. Barillari, M. Barisonzi, T. Barklow, N. Barlow, S. L. Barnes, B. M. Barnett, R. M. Barnett, Z. Barnovska, A. Baroncelli, G. Barone, A. J. Barr, F. Barreiro, J. Barreiro Guimarães da Costa, R. Bartoldus, A. E. Barton, P. Bartos, A. Basalaev, A. Bassalat, A. Basye, R. L. Bates, S. J. Batista, J. R. Batley, M. Battaglia, M. Bauce, F. Bauer, H. S. Bawa, J. B. Beacham, M. D. Beattie, T. Beau, P. H. Beauchemin, R. Beccherle, P. Bechtle, H. P. Beck, K. Becker, M. Becker, M. Beckingham, C. Becot, A. J. Beddall, A. Beddall, V. A. Bednyakov, C. P. Bee, L. J. Beemster, T. A. Beermann, M. Begel, J. K. Behr, C. Belanger-Champagne, W. H. Bell, G. Bella, L. Bellagamba, A. Bellerive, M. Bellomo, K. Belotskiy, O. Beltramello, O. Benary, D. Benchekroun, M. Bender, K. Bendtz, N. Benekos, Y. Benhammou, E. Benhar Noccioli, J. A. Benitez Garcia, D. P. Benjamin, J. R. Bensinger, S. Bentvelsen, L. Beresford, M. Beretta, D. Berge, E. Bergeaas Kuutmann, N. Berger, F. Berghaus, J. Beringer, C. Bernard, N. R. Bernard, C. Bernius, F. U. Bernlochner, T. Berry, P. Berta, C. Bertella, G. Bertoli, F. Bertolucci, C. Bertsche, D. Bertsche, M. I. Besana, G. J. Besjes, O. Bessidskaia Bylund, M. Bessner, N. Besson, C. Betancourt, S. Bethke, A. J. Bevan, W. Bhimji, R. M. Bianchi, L. Bianchini, M. Bianco, O. Biebel, D. Biedermann, S. P. Bieniek, M. Biglietti, J. Bilbao De Mendizabal, H. Bilokon, M. Bindi, S. Binet, A. Bingul, C. Bini, S. Biondi, C. W. Black, J. E. Black, K. M. Black, D. Blackburn, R. E. Blair, J.-B. Blanchard, J. E. Blanco, T. Blazek, I. Bloch, C. Blocker, W. Blum, U. Blumenschein, G. J. Bobbink, V. S. Bobrovnikov, S. S. Bocchetta, A. Bocci, C. Bock, M. Boehler, J. A. Bogaerts, D. Bogavac, A. G. Bogdanchikov, C. Bohm, V. Boisvert, T. Bold, V. Boldea, A. S. Boldyrev, M. Bomben, M. Bona, M. Boonekamp, A. Borisov, G. Borissov, S. Borroni, J. Bortfeldt, V. Bortolotto, K. Bos, D. Boscherini, M. Bosman, J. Boudreau, J. Bouffard, E. V. Bouhova-Thacker, D. Boumediene, C. Bourdarios, N. Bousson, A. Boveia, J. Boyd, I. R. Boyko, I. Bozic, J. Bracinik, A. Brandt, G. Brandt, O. Brandt, U. Bratzler, B. Brau, J. E. Brau, H. M. Braun, S. F. Brazzale, W. D. Breaden Madden, K. Brendlinger, A. J. Brennan, L. Brenner, R. Brenner, S. Bressler, K. Bristow, T. M. Bristow, D. Britton, D. Britzger, F. M. Brochu, I. Brock, R. Brock, J. Bronner, G. Brooijmans, T. Brooks, W. K. Brooks, J. Brosamer, E. Brost, J. Brown, P. A. Bruckman de Renstrom, D. Bruncko, R. Bruneliere, A. Bruni, G. Bruni, M. Bruschi, N. Bruscino, L. Bryngemark, T. Buanes, Q. Buat, P. Buchholz, A. G. Buckley, S. I. Buda, I. A. Budagov, F. Buehrer, L. Bugge, M. K. Bugge, O. Bulekov, D. Bullock, H. Burckhart, S. Burdin, C. D. Burgard, B. Burghgrave, S. Burke, I. Burmeister, E. Busato, D. Büscher, V. Büscher, P. Bussey, J. M. Butler, A. I. Butt, C. M. Buttar, J. M. Butterworth, P. Butti, W. Buttinger, A. Buzatu, A. R. Buzykaev, S. Cabrera Urbán, D. Caforio, V. M. Cairo, O. Cakir, N. Calace, P. Calafiura, A. Calandri, G. Calderini, P. Calfayan, L. P. Caloba, D. Calvet, S. Calvet, R. Camacho Toro, S. Camarda, P. Camarri, D. Cameron, R. Caminal Armadans, S. Campana, M. Campanelli, A. Campoverde, V. Canale, A. Canepa, M. Cano Bret, J. Cantero, R. Cantrill, T. Cao, M. D. M. Capeans Garrido, I. Caprini, M. Caprini, M. Capua, R. Caputo, R. Cardarelli, F. Cardillo, T. Carli, G. Carlino, L. Carminati, S. Caron, E. Carquin, G. D. Carrillo-Montoya, J. R. Carter, J. Carvalho, D. Casadei, M. P. Casado, M. Casolino, E. Castaneda-Miranda, A. Castelli, V. Castillo Gimenez, N. F. Castro, P. Catastini, A. Catinaccio, J. R. Catmore, A. Cattai, J. Caudron, V. Cavaliere, D. Cavalli, M. Cavalli-Sforza, V. Cavasinni, F. Ceradini, B. C. Cerio, K. Cerny, A. S. Cerqueira, A. Cerri, L. Cerrito, F. Cerutti, M. Cerv, A. Cervelli, S. A. Cetin, A. Chafaq, D. Chakraborty, I. Chalupkova, P. Chang, J. D. Chapman, D. G. Charlton, C. C. Chau, C. A. Chavez Barajas, S. Cheatham, A. Chegwidden, S. Chekanov, S. V. Chekulaev, G. A. Chelkov, M. A. Chelstowska, C. Chen, H. Chen, K. Chen, L. Chen, S. Chen, X. Chen, Y. Chen, H. C. Cheng, Y. Cheng, A. Cheplakov, E. 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Valladolid Gallego, S. Vallecorsa, J. A. Valls Ferrer, W. Van Den Wollenberg, P. C. Van Der Deijl, R. van der Geer, H. van der Graaf, N. van Eldik, P. van Gemmeren, J. Van Nieuwkoop, I. van Vulpen, M. C. van Woerden, M. Vanadia, W. Vandelli, R. Vanguri, A. Vaniachine, F. Vannucci, G. Vardanyan, R. Vari, E. W. Varnes, T. Varol, D. Varouchas, A. Vartapetian, K. E. Varvell, F. Vazeille, T. Vazquez Schroeder, J. Veatch, L. M. Veloce, F. Veloso, T. Velz, S. Veneziano, A. Ventura, D. Ventura, M. Venturi, N. Venturi, A. Venturini, V. Vercesi, M. Verducci, W. Verkerke, J. C. Vermeulen, A. Vest, M. C. Vetterli, O. Viazlo, I. Vichou, T. Vickey, O. E. Vickey Boeriu, G. H. A. Viehhauser, S. Viel, R. Vigne, M. Villa, M. Villaplana Perez, E. Vilucchi, M. G. Vincter, V. B. Vinogradov, I. Vivarelli, F. Vives Vaque, S. Vlachos, D. Vladoiu, M. Vlasak, M. Vogel, P. Vokac, G. Volpi, M. Volpi, H. von der Schmitt, H. von Radziewski, E. von Toerne, V. Vorobel, K. Vorobev, M. Vos, R. Voss, J. H. Vossebeld, N. Vranjes, M. Vranjes Milosavljevic, V. Vrba, M. Vreeswijk, R. Vuillermet, I. Vukotic, Z. Vykydal, P. Wagner, W. Wagner, H. Wahlberg, S. Wahrmund, J. Wakabayashi, J. Walder, R. Walker, W. Walkowiak, C. Wang, F. Wang, H. Wang, J. Wang, K. Wang, R. Wang, S. M. Wang, T. Wang, X. Wang, C. Wanotayaroj, A. Warburton, C. P. Ward, D. R. Wardrope, A. Washbrook, C. Wasicki, P. M. Watkins, A. T. Watson, I. J. Watson, M. F. Watson, G. Watts, S. Watts, B. M. Waugh, S. Webb, M. S. Weber, S. W. Weber, J. S. Webster, A. R. Weidberg, B. Weinert, J. Weingarten, C. Weiser, H. Weits, P. S. Wells, T. Wenaus, T. Wengler, S. Wenig, N. Wermes, M. Werner, P. Werner, M. Wessels, J. Wetter, K. Whalen, A. M. Wharton, A. White, M. J. White, R. White, S. White, D. Whiteson, F. J. Wickens, W. Wiedenmann, M. Wielers, P. Wienemann, C. Wiglesworth, L. A. M. Wiik-Fuchs, A. Wildauer, H. G. Wilkens, H. H. Williams, S. Williams, C. Willis, S. Willocq, A. Wilson, J. A. Wilson, I. Wingerter-Seez, F. Winklmeier, B. T. Winter, M. Wittgen, J. Wittkowski, S. J. Wollstadt, M. W. Wolter, H. Wolters, B. K. Wosiek, J. Wotschack, M. J. Woudstra, K. W. Wozniak, M. Wu, S. L. Wu, X. Wu, Y. Wu, T. R. Wyatt, B. M. Wynne, S. Xella, D. Xu, L. Xu, B. Yabsley, S. Yacoob, R. Yakabe, M. Yamada, D. Yamaguchi, Y. Yamaguchi, A. Yamamoto, S. Yamamoto, T. Yamanaka, K. Yamauchi, Y. Yamazaki, Z. Yan, H. Yang, Y. Yang, W-M. Yao, Y. Yasu, E. Yatsenko, K. H. Yau Wong, J. Ye, S. Ye, I. Yeletskikh, A. L. Yen, E. Yildirim, K. Yorita, R. Yoshida, K. Yoshihara, C. Young, C. J. S. Young, S. Youssef, D. R. Yu, J. Yu, J. M. Yu, L. Yuan, S. P. Y. Yuen, A. Yurkewicz, I. Yusuff, B. Zabinski, R. Zaidan, A. M. Zaitsev, J. Zalieckas, A. Zaman, S. Zambito, L. Zanello, D. Zanzi, C. Zeitnitz, M. Zeman, A. Zemla, Q. Zeng, K. Zengel, O. Zenin, T. Ženiš, D. Zerwas, D. Zhang, F. Zhang, H. Zhang, J. Zhang, L. Zhang, R. Zhang, X. Zhang, Z. Zhang, X. Zhao, Y. Zhao, Z. Zhao, A. Zhemchugov, J. Zhong, B. Zhou, C. Zhou, L. Zhou, M. Zhou, N. Zhou, C. G. Zhu, H. Zhu, J. Zhu, Y. Zhu, X. Zhuang, K. Zhukov, A. Zibell, D. Zieminska, N. I. Zimine, C. Zimmermann, S. Zimmermann, Z. Zinonos, M. Zinser, M. Ziolkowski, L. Živković, G. Zobernig, A. Zoccoli, M. zur Nedden, G. Zurzolo, L. Zwalinski, and ATLAS Collaboration

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Published
2022
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42. Development of specific immunity in laboratory animals after co-immunization against seasonal influenza and COVID-19

Author

G. M. Ignatyev, I. A. Leneva, A. V. Atrasheuskaya, L. I. Kozlovskaya, N. P. Kartashova, I. T. Fediakina, E. Yu. Shustova, A. A. Sinyugina, V. V. Zverev, V. P. Trukhin, and A. A. Ishmukhametov

Subjects
influenza, sars-cov-2, co-vaccination, Microbiology, QR1-502
Abstract

Introduction. In clinical practice, the differential diagnosis of COVID-19 can be challenging during the flu season, entailing serious consequences such as delays in appropriate control measures against the SARS-CoV-2 pandemic. Another problem is posed by co-infection of SARS-CoV-2 and influenza virus (IV), which significantly contributes to the severity of the COVID-19 disease. This study was aimed to explore the cross-impact of co-administration of Russian influenza and COVID-19 vaccines on development of specific immunity in laboratory animals.Materials and methods. The study was conducted on BALB/c mice. The animals were inoculated intramuscularly with the vaccine for COVID-19 prevention (CoviVac) and the vaccine for influenza prevention (Flu-M). The sera from the immunized animals were examined separately. Three IV strains were used in the hemagglutination inhibition assay. Antibodies (Abs) against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA). The neutralization test was performed to detect virus neutralizing antibodies against SARS-CoV-2 and IV.Results. Relatively high titers of specific Abs were found in the groups of animals inoculated with one vaccine and with two vaccines concurrently. In the groups of animals inoculated with CoviVac and with two vaccines concurrently, both in the ELISA test and in the neutralization test, the average titers of specific Abs against SARSCoV- 2 did not demonstrate any statistical difference. The group of animals inoculated concurrently with two vaccines demonstrated statistically higher titers of Abs against IV after the second immunization compared to the group of animals inoculated with Flu-M.Discussion. The study has shown that post-vaccination immunity both to IV and to SARS-CoV-2 develops after co-vaccination with two vaccines. The observed enhanced post-vaccination immune response to IV in the coimmunized laboratory animals needs further research.Conclusion. The performed studies suggest the possibility of co-administration of two vaccines to prevent influenza and COVID-19.

Published
2022
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43. SARS-CoV-2 infection in children in Moscow in 2020: clinical features and impact on circulation of other respiratory viruses: SARS-CoV-2 infection in children in Moscow in 2020

Author

Yakovlev, Alexander S., Belyaletdinova, Ilmira K., Mazankova, Lyudmila N., Samitova, Elmira R., Osmanov, Ismail M., Gavelya, Nataly V., Volok, Viktor P., Kolpakova, Ekaterina S., Shishova, Anna A., Dracheva, Natalia A., Kozlovskaya, Liubov I., Karganova, Galina G., and Ishmukhametov, Aydar A.

Published
2022
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44. Ensemble docking based virtual screening of SARS‐CoV‐2 main protease inhibitors.

Author

Fomina, Anastasia D., Uvarova, Victoria I., Kozlovskaya, Liubov I., Palyulin, Vladimir A., Osolodkin, Dmitry I., and Ishmukhametov, Aydar A.

Subjects
CORONAVIRUSES, PROTEASE inhibitors, DRUG target, DATA integrity, COVID-19
Abstract

During the first years of COVID‐19 pandemic, X‐ray structures of the coronavirus drug targets were acquired at an unprecedented rate, giving hundreds of PDB depositions in less than a year. The main protease (Mpro) of severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) is the primary validated target of direct‐acting antivirals. The selection of the optimal ensemble of structures of Mpro for the docking‐driven virtual screening campaign was thus non‐trivial and required a systematic and automated approach. Here we report a semi‐automated active site RMSD based procedure of ensemble selection from the SARS‐CoV‐2 Mpro crystallographic data and virtual screening of its inhibitors. The procedure was compared with other approaches to ensemble selection and validated with the help of hand‐picked and peer‐reviewed activity‐annotated libraries. Prospective virtual screening of non‐covalent Mpro inhibitors resulted in a new chemotype of thienopyrimidinone derivatives with experimentally confirmed enzyme inhibition. [ABSTRACT FROM AUTHOR]

Published
2024
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45. The Specificity of Epizootic and Epidemiological Processes in Natural Foci of Hemorrhagic Fever with Renal Syndrome and Tick-Borne Encephalitis in Russia, as the Basis for the Prospects of Creating a Combined Vaccine for the Prevention of These Infections

Author

Tkachenko, Evgeniy, Balkina, Alexandra, Trankvilevsky, Dmitriy, Kolyasnikova, Nadezda, Teodorovich, Rostislav, Vorovich, Mikhail, Popova, Yulia, Kurashova, Svetlana, Egorova, Maria, Belyakova, Alla, Tkachenko, Petr, Ishmukhametov, Aydar, and Dzagurova, Tamara

Subjects
HEMORRHAGIC fever with renal syndrome, TICK-borne encephalitis, VIRUS diseases, COMBINED vaccines, INFECTION prevention
Abstract

Hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) are the most common viral diseases in Russia. HFRS is caused by six different types of hantaviruses: Hantaan, Amur, Seoul, Puumala, Kurkino, and Sochi, which are transmitted to humans through small mammals of the Muridae and Cricetidae families. TBE is caused by viruses belonging to five different phylogenetic subtypes. The similarities in the ecology of HFRS and TBE pathogens is presented here. Hantavirus-infected small mammals can transmit the virus to uninfected animals, and ticks can also transmit hantavirus to other ticks and mammals. Hantavirus transmission from ticks to humans is possible only hypothetically based on indirect data. Over the past 23 years, 164,582 cases of HFRS (4.9 per 105 people) and 71,579 cases of TBE (2.5 per 105 people) were registered in Russia. The mortality rate was 0.4% (668 cases) in HFRS and 1.6% deaths (1136 cases) in TBE. There were 4030 HFRS (2.5%) and 9414 TBE (13%) cases in children under 14 years old. HFRS and TBE cases were registered in 42 out of 85 Russian regions; in 18—only HFRS, in 13—only TBE, and 12 had no reported cases. The prospects of applying a combined vaccine for HFRS and TBE prevention are shown in this paper. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Prevalence and Clinical Impact of Viral and Bacterial Coinfections in Hospitalized Children and Adolescents Aged under 18 Years with COVID-19 during the Omicron Wave in Russia.

Author

Yakovlev, Alexander S., Afanasev, Vladislav V., Alekseenko, Svetlana I., Belyaletdinova, Ilmira K., Isankina, Ludmila N., Gryaznova, Irina A., Skalny, Anatoly V., Kozlovskaya, Liubov I., Ishmukhametov, Aydar A., and Karganova, Galina G.

Subjects
SARS-CoV-2 Omicron variant, COVID-19 pandemic, CHILD patients, HOSPITAL care of children, MIXED infections, SARS-CoV-2
Abstract

The COVID-19 pandemic has altered respiratory infection patterns in pediatric populations. The emergence of the SARS-CoV-2 Omicron variant and relaxation of public health measures have increased the likelihood of coinfections. Previous studies show conflicting results regarding the impact of viral and bacterial coinfections with SARS-CoV-2 on severity of pediatric disease. This study investigated the prevalence and clinical impact of coinfections among children hospitalized with COVID-19 during the Omicron wave. A retrospective analysis was conducted on 574 hospitalized patients aged under 18 years in Russia, from January 2022 to March 2023. Samples from patients were tested for SARS-CoV-2 and other respiratory pathogens using qRT-PCR, bacterial culture tests and mass spectrometry, and ELISA. Approximately one-third of COVID-19 cases had coinfections, with viral and bacterial coinfections occurring at similar rates. Adenovirus and Staphylococcus aureus were the most common viral and bacterial coinfections, respectively. Viral coinfections were associated with higher fevers and increased bronchitis, while bacterial coinfections correlated with longer duration of illness and higher pneumonia rates. Non-SARS-CoV-2 respiratory viruses were linked to more severe lower respiratory tract complications than SARS-CoV-2 monoinfection. These findings suggest that during the Omicron wave, seasonal respiratory viruses may have posed a greater threat to children's health than SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Published
2024
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47. An Integrative Approach to the Study of Cognitive Abilities in a Non-Human Primate Model in a Virology Laboratory Environment.

Author

Rogova, Anastasia, Kalyanova, Anna, Rogova, Yulia, Fedina, Maria, Siniugina, Alexandra, Ishmukhametov, Aydar, and Karganova, Galina

Subjects
REINFORCEMENT (Psychology), COGNITIVE testing, KRA, AIRBORNE infection, VIRUS diseases
Abstract

Non-human primates, due to their similarities in immune response to humans, are the preferred model for studying infectious processes and any associated cognitive impairments. Behavioral tests are indispensable for investigating pathogenesis in neuroinfections, especially those that do not manifest with noticeable clinical symptoms, as well as in the transition to a chronic form of the disease. Modeling viral infection requires specialized experimental conditions. Our work describes techniques for investigating mnemonic functions, tiredness, attentional focus, quick-wittedness, and basic behavioral responses in primates under the assumed conditions for infections with viruses that do not have an airborne route of transmission. It also outlines approaches to the training and selection of primates for virological research, as well as analyzing gender differences in learning abilities, the impact of housing conditions on the results, and the correlation between training success and behavioral test scores. These methods will allow a more detailed study of non-human primates as a model for researching cognitive and behavioral impairments under infectious and immune stress, as well as the design of less energy-intensive experiments for evaluating the efficacy and safety of therapeutic and prophylactic strategies at early stages of infection. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Flaviviruses in AntiTumor Therapy

Author

Alina S. Nazarenko, Mikhail F. Vorovitch, Yulia K. Biryukova, Nikolay B. Pestov, Ekaterina A. Orlova, Nickolai A. Barlev, Nadezhda M. Kolyasnikova, and Aydar A. Ishmukhametov

Subjects
oncolytic viruses, flavivirus, immunotherapy, viral vector, recombinant strain, cancer immunotherapy, Microbiology, QR1-502
Abstract

Oncolytic viruses offer a promising approach to tumor treatment. These viruses not only have a direct lytic effect on tumor cells but can also modify the tumor microenvironment and activate antitumor immunity. Due to their high pathogenicity, flaviviruses have often been overlooked as potential antitumor agents. However, with recent advancements in genetic engineering techniques, an extensive history with vaccine strains, and the development of new attenuated vaccine strains, there has been a renewed interest in the Flavivirus genus. Flaviviruses can be genetically modified to express transgenes at acceptable levels, and the stability of such constructs has been greatly improving over the years. The key advantages of flaviviruses include their reproduction cycle occurring entirely within the cytoplasm (avoiding genome integration) and their ability to cross the blood–brain barrier, facilitating the systemic delivery of oncolytics against brain tumors. So far, the direct lytic effects and immunomodulatory activities of many flaviviruses have been widely studied in experimental animal models across various types of tumors. In this review, we delve into the findings of these studies and contemplate the promising potential of flaviviruses in oncolytic therapies.

Published
2023
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49. Safety and Immunogenicity of Inactivated Whole Virion COVID-19 Vaccine CoviVac in Clinical Trials in 18–60 and 60+ Age Cohorts

Author

Ilya V. Gordeychuk, Liubov I. Kozlovskaya, Aleksandra A. Siniugina, Nadezhda V. Yagovkina, Vladimir I. Kuzubov, Konstantin A. Zakharov, Viktor P. Volok, Maria S. Dodina, Larissa V. Gmyl, Natalya A. Korotina, Rostislav D. Theodorovich, Yulia I. Ulitina, Dmitry I. Vovk, Marina V. Alikova, Anna A. Kataeva, Anna V. Kalenskaya, Irina V. Solovjeva, Elena V. Tivanova, Larissa Y. Kondrasheva, Antonina A. Ploskireva, Vasiliy G. Akimkin, Ksenia A. Subbotina, Georgy M. Ignatyev, Anastasia K. Korduban, Elena Y. Shustova, Ekaterina O. Bayurova, Alla S. Zhitkevich, Daria V. Avdoshina, Anastasia N. Piniaeva, Anastasia A. Kovpak, Liliya P. Antonova, Yulia V. Rogova, Anna A. Shishova, Yury Y. Ivin, Svetlana E. Sotskova, Konstantin A. Chernov, Elena G. Ipatova, Ekaterina A. Korduban, and Aydar A. Ishmukhametov

Subjects
COVID-19, inactivated vaccine, neutralizing antibodies, phase I-II clinical trials, 18–60 age cohort, 60+ age cohort, Microbiology, QR1-502
Abstract

We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial phase I/II of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in volunteers aged 18–60 and open multi-center comparative phase IIb clinical trial in volunteers aged 60 years and older. The safety of the vaccine was assessed in 400 volunteers in the 18–60 age cohort who received two doses of the vaccine (n = 300) or placebo (n = 100) and in 200 volunteers in 60+ age cohort all of whom received three doses of the vaccine. The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AEs), or other significant AEs related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p < 0.05). Immunogenicity assessment in stage 3 of Phase II was performed on 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening. On Day 42 after the 1st vaccination, the seroconversion rate in participants who were seronegative at screening was 86.9%, with the average geometric mean neutralizing antibody (nAB) titer of 1:20. A statistically significant (p < 0.05) increase in IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the 1st vaccination. In participants who were seropositive at screening but had nAB titers below 1:256, the rate of fourfold increase in nAB levels was 85.2%, while in the participants with nAB titers > 1:256, the rate of fourfold increase in nAB levels was below 45%; the participants who were seropositive at screening of the 2nd vaccination did not lead to a significant increase in nAB titers. In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with over 85% NT seroconversion rates after complete vaccination course in participants who were seronegative at screening in both age groups: 18–60 and 60+. In participants who were seropositive at screening and had nAB titers below 1:256, a single vaccination led to a fourfold increase in nAB levels in 85.2% of cases. These findings indicate that CoviVac can be successfully used both for primary vaccination in a two-dose regimen and for booster vaccination as a single dose in individuals with reduced neutralizing antibody levels.

Published
2023
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50. Cases of Hemorrhagic Fever with Renal Syndrome in Russia during 2000–2022

Author

Evgeniy Tkachenko, Svetlana Kurashova, Alexandra Balkina, Alexander Ivanov, Mariya Egorova, Oksana Leonovich, Yulia Popova, Rostislav Teodorovich, Alla Belyakova, Petr Tkachenko, Dmitriy Trankvilevsky, Ekaterina Blinova, Aydar Ishmukhametov, and Tamara Dzagurova

Subjects
orthohantavirus, hemorrhagic fever with renal syndrome, zoonotic viral diseases, epidemics, morbidity, incidence rate, Microbiology, QR1-502
Abstract

During 2000–2022, a total of 69 of Russia’s 85 administrative regions reported 164,580 hemorrhagic fever with renal syndrome (HFRS) cases, with an annual average rate of 4.9 cases/100,000 population (105 popul.). European Russia reported 162,045 (98.5%) cases in 53/60 regions with 9.7 cases/105 popul. Asian Russia reported 2535 (1.5%) cases in 16/25 regions with 0.6 cases/105 popul. In the same period, Russia reported 668 (0.4%) fatal HFRS cases, and 4030 (2.4%) cases among children under the age of 14 years. Most HFRS cases occurred during autumn and winter. The incidence among rural residents was 6.7 per 105 popul., higher than the urban 4.4 per 105 popul.; however, among HFRS patients, rural and urban residents account for 35% and 65%, respectively. Six hantaviruses, causing HFRS of different clinical severity, were recognized as pathogens: Hantaan (HTNV) and Amur (AMUV) of Orthohantavirus hantanense species, Seoul (SEOV) of Orthohantavirus seoulense species, Puumala (PUUV) of Orthohantavirus puumalaense species, and Kurkino (KURV) and Sochi (SOCV) of Orthohantavirus dobravaense species, with the principal hosts Apodemus agrarius coreae, Apodemus peninsulae, Rattus norvegicus, Myodes glareolus, Apodemus agrarius agrarius, and Sylvaemus ponticus, respectively. It was found that 97.7% of HFRS cases are caused by PUUV, therefore, this virus plays the main role in the HFRS morbidity structure in Russia.

Published
2023
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