FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology
Objective: to perform a clinical and economic analysis of using drugs containing follitropin alfa... more Objective: to perform a clinical and economic analysis of using drugs containing follitropin alfa as an active substance and to assess the impact of the studied drugs on the budget of the state healthcare system of the Russian Federation considering cost data for 2022 in the population of women with infertility and poor ovarian response who are undergoing treatment with the use of assisted reproductive technologies (ART).Material and methods. Clinical and economic evaluation of follitropin alfa use in patients with infertility and poor ovarian response was performed by a cost minimization method, using data from the Uniform Information System for Procurement for the period from July to December 2022 inclusive. The budget impact analysis model compared the costs required for ovarian stimulation of patients with poor ovarian response receiving only a fixed dose combination (FDC) of follitropin alfa + lutropin alfa with the expected practice of switching 25% of these patients to follit...
Relevance. Combined foci of zoonotic infections are found in all regions of the Russian Federatio... more Relevance. Combined foci of zoonotic infections are found in all regions of the Russian Federation. A feature of combined foci is the common biocenosis for populations of pathogens of various etiologies (bacteria, viruses, parasitic infections) and the formation of natural foci by them. Aim. Epizootological study of the territory in the south of the Arkhangelsk region for the presence of combined foci of zoonotic infections (tularemia, leptospirosis and hemorrhagic fever with renal syndrome – HFRS). Materials and methods. 135 small mammals were captured and examined in the Ustyansky district of the Arkhangelsk region. Established the species composition and mixed infection among small mammals pathogens of tularemia, leptospirosis, hemorrhagic fever with renal syndrome. Results. In the south of the Arkhangelsk Region in the Ustyansky District, in 2019, for the first time, a combined natural focus of the forest type was identified and characterized. The bank vole and the common shrew ...
Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination... more Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by obvious shortage in supply of licensed vaccines. Development of new vaccines that are easy to manufacture and administer is highly desirable to overcome hurdles in vaccine scaling up and distribution, especially in developing countries. In the effort to satisfy vaccine demands we developed a new single dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein – “Sputnik Light”. Methods: We conducted an open label, two-stage, prospective, non-randomized phase I-II trial aimed to assess safety, tolerability and immunogenicity of “Sputnik Light” vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-Cov2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). The trial is registered at ClinicalTrials.gov (NCT04713488). Findings: Between January 14 and 27, 2021, 150 participants were screened, of whom 110 were enrolled. Most of solicited adverse reactions were mild (66.4% from all vaccinees), few were moderate (5.5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-Cov2 antibodies revealed group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data according to pre-existing immunity to SARS-Cov2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (GMT) 594.4 at a baseline up to 26899 comparing to 29.09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time in seropositive group seroconversion rate by day 42 was 92.9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81.7% (76/93) and 92.9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15.18 and 579.7 in the seronegative and seropositive groups, respectively. Each test to assess cell-mediated immune reactions was carried out on a separate group of 30 volunteers on day 10 upon vaccination. Antigen-specific T cell proliferation, formation of IFNy-producing cells, as well as IFNy secretion were detected in 96.7% (26/27), 96% (24/25) and 96% (24/25) seronegative and in 100% (3/3) 100% (5/5) and 100% (5/5) seropositive vaccinees, correspondingly. Interpretation: The single dose rAd26 vector-based COVID-19 vaccine “Sputnik Light” has a good safety profile and induced strong humoral and cellular immune responses both in seronegative and seropositive participants. Further investigation is needed to assess the effectiveness of this vaccine against COVID-19 used for primary and secondary vaccination. Clinical Trial Registration Details: The trial is registered at ClinicalTrials.gov (NCT04713488). Funding Information: Russian Direct Investment Fund. Declaration of Interests: OVZ, TAO, IVD, OP, DVS, DMG, ASD, AIT, DNS, IBE, EAT, AGB, ASE, FMI, NAN, NLL, ASS, SVB, BSN, DYL, ALG report patents for an immunobiological expression vector, pharmaceutical agent, and its method of use to prevent COVID-19. All other authors declare no competing interests. Ethics Approval Statement: The trial was approved by the local ethic committee and was conducted with the approval of the Ministry of Health of Russian Federation in compliance with International Conference on Harmonization and National Good Clinical Practice guidelines and Declaration of Helsinki.
The influence of both, the composite material based on the protein-mineral components including t... more The influence of both, the composite material based on the protein-mineral components including the prolonged form of the recombinant human bone morphogenetic protein 2 (rhBMP-2) and the method of the titanium implant's surface treatment, on the reparative osteogenesis and adhesion strength of the bone tissue – implant's surface contact was evaluated. Covering of implants with the composite coating promotes significant acceleration of the bone tissue regeneration processes in the site of implants loading. The composition coating with prolonged form of the rhBMP-2 promoted increasing of the neogenic bone tissue's adhesion with the implants, as compared with the coating without recombinant human bone morphogenetic protein. The implants treated with microarc oxidation demonstrated higher values of the breakout force during the separation of the implants from the bone than the implants treated with sandblasting method.
Семихин Александр Сергеевич – канд. биол. наук, ст. науч. сотр.,Котнова Алина Петровна – канд. хи... more Семихин Александр Сергеевич – канд. биол. наук, ст. науч. сотр.,Котнова Алина Петровна – канд. хим. наук, науч. сотр.,Башкиров Виктор Николаевич – канд. биол. наук, ст. науч. сотр., e-mail: [email protected],Карягина-Жулина Анна Станиславовна – д-р биол. наук, гл. науч. сотр., e-mail: akaryagina@ gmail.com,Лунин Владимир Глебович – д-р биол. наук, зав. лаб., e-mail: [email protected],Гинцбург Александр Леонидович – акад. РАМН, д-р биол. наук, проф., дир.Институт инженерной иммунологииКуликова Наталья Леонидовна – ст. науч. сотр.,Хлебников Валентин Сергеевич – д-р биол. наук, проф., зав. лаб.,Центральный НИИ туберкулеза РАМНКондратьева Татьяна Константиновна – д-р биол. наук, вед. науч. сотр.,Апт Александр Соломонович – д-р биол. наук, проф., зав. лаб.,НИИ Фхб им. А.Н. белозерского МГУВеселов Андрей Михайлович – аспирант.
Background While the world is experiencing another wave of COVID-19 pandemic, global vaccination ... more Background While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by an evident shortage in the supply of licensed vaccines. In an effort to satisfy vaccine demands we developed a new single-dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein – “Sputnik Light”. Methods We conducted an open label, prospective, non-randomised phase 1/2 trial aimed to assess safety, tolerability, and immunogenicity of “Sputnik Light” vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-CoV-2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). Findings Most of the solicited adverse reactions were mild (66·4% from all vaccinees), few were moderate (5·5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-CoV-2 antibodies revealed a group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data based on pre-existing immunity to SARS-CoV-2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (GMT) 594·4 at a baseline up to 26899 comparing to 29·09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time, in the seropositive group, seroconversion rate by day 42 was 92·9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81·7% (76/93) and 92·9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15·18 and 579·7 in the seronegative and seropositive groups, respectively. Antigen-specific T cell proliferation, formation of IFNy-producing cells, and IFNy secretion were observed in 96·7% (26/27), 96% (24/25), and 96% (24/25) of the seronegative group respectively and in 100% (3/3), 100% (5/5), and 100% (5/5) of the seropositive vaccinees, respectively. Interpretation The single-dose rAd26 vector-based COVID-19 vaccine “Sputnik Light” has a good safety profile and induces a strong humoral and cellular immune responses both in seronegative and seropositive participants. Funding Russian Direct Investment Fund.
ObjectivesVaccination remains the most effective response to the COVID-19 pandemic. Most vaccines... more ObjectivesVaccination remains the most effective response to the COVID-19 pandemic. Most vaccines use two-dose regimens. In turn, single-dose vaccines also have high potential, since, on the one hand, they simplify the vaccination program, make it more accessible and convenient for more people around the world, and on the other hand, they are better suited for subsequent revaccination. However, there is not enough data on the effectiveness of single-dose vaccine variants against new genetic lines to assess their current potential. It is not clear how much a single dose of immunization protects against the globally dominant delta variant. In this work, we investigated the effectiveness of a single dose vaccine (Sputnik Light, the first component of Sputnik V vaccine) against the Delta variant in Moscow.MethodsTo assess the effectiveness of one dose of viral vector vaccine based on rAd26 against the delta variant in Moscow, we used data from the Moscow registries of vaccination agains...
BACKGROUND Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunog... more BACKGROUND Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4·5 h after symptom onset. METHODS We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0-1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. FINDINGS Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89-89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1·47, 95% CI 0·93 to 2·32; p=0·10). The difference in the rate of favourable outcome at day 90 was 9·5% (95% CI -1·7 to 20·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0·044). INTERPRETATION Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. FUNDING The Russian Academy of Sciences.
Molekuliarnaia genetika, mikrobiologiia i virusologiia, 2012
Protein genes Ag85A, Esat-6, and Cfp10 of Mycobacterium tuberculosis were sequenced using the dat... more Protein genes Ag85A, Esat-6, and Cfp10 of Mycobacterium tuberculosis were sequenced using the database GenBank to implement selection and synthesis of primer pairs of given genes. PCR was used to obtain target amplicons of the genes. Chromosome DNA of M. tuberculosis H37Rv was used as the DNA amplification matrix. The PCR products were obtained using the plasmid pQE6, cloned, and amplified in the Escherichia coli M15 strain. Chimere products containing mycobacterial genes and cellulose binding protein domain (CBD), were obtained using the plasmid treated with restriction endonucleases. CBD fragment obtained using similar treatment of the ptt10 plasmid. The plasmids containing merged sequences of mycobacterial genes-antigenes and CBD were selected. The 3 mycobacterial genes were expressed in the E. coli M15 cells resulting in biosynthesis of corresponding recombinant proteins of expected molecular weight. Concentration of CBD, Cfp10-CBD, Ag85A-CBD, and ESAT6-CBD was 20%, 15%, and 15%...
Molekuliarnaia genetika, mikrobiologiia i virusologiia, 2009
Fusion gene consisting of dextran-binding domain from Leuconostoc mesenteroides subsp. Mesenteroi... more Fusion gene consisting of dextran-binding domain from Leuconostoc mesenteroides subsp. Mesenteroides (DBD) and human recombinant interferon-beta (IFN-beta) incorporated between the nucleotide sequence encoding for the recognition site of human enteropeptidase (DDDDK) was installed and constructed in Escherichia coli. The overproducing strain of the chimeric protein DBD-IFN-beta consisting of the IFN-beta, spacer including 10 GS-repeats, human enteropeptidase recognition site, and dextran-binding domain from Leuconostoc mesenteroides was constructed. Free human recombinant interferon-beta was obtained as a result of treatment of the chimeric protein DBD-IFN-beta immobilized on sephadex G-25 with human enteropeptidase. The ability of free and immobilized protein to protect human cells from viral infection was demonstrated. The developed approach can be used for purification of the recombinant proteins with different biological activity and possible construction of new immunostimulatin...
Bone morphogenetic protein-2 (rhBMP-2) represents the osteoinductive protein factor which plays a... more Bone morphogenetic protein-2 (rhBMP-2) represents the osteoinductive protein factor which plays a dominant role in growth and regeneration of a bone tissue. In clinical practice the bone grafting materials on the basis of rhBMP-2 are widely applied; the Russian analogues of similar materials are not produced. The fragment of the bmp2gene coding for a mature protein was cloned in Escherichia coli. The effective overproducing strain of rhBMP-2 was created on a basis of the E. coli BL21 (DE3). The rhBMP-2 production was about 25% of total cell protein. The biologically active dimeric form of rhBMP-2 was obtained by isolation and purification of protein from inclusion bodies with subsequent refolding. The rhBMP-2 sample with more than 80% of the dimeric form was obtained, which is able to interact with specific antibodies to BMP-2. Biological activity of the received rhBMP-2 samples was shown in the in vitro experiments by induction of alkaline phosphatase synthesis in C2C12 and C3H10T1/2 cell cultures. On model of the ectopic osteogenesis it was shown that received rhBMP-2 possesses biological activity in vivo, causing tissue calcification in the place of an injection. The protein activity in vivo depends on way of protein introduction and characteristics of protein sample: rhBMP-2 may be introduced in an acid or basic buffer solution, with or without the carrier. The offered method of rhBMP-2 isolation and purification results in increasing common protein yield as well as the maintenance of biologically active dimeric form in comparison with the analogues described in the literature.
FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology
Objective: to perform a clinical and economic analysis of using drugs containing follitropin alfa... more Objective: to perform a clinical and economic analysis of using drugs containing follitropin alfa as an active substance and to assess the impact of the studied drugs on the budget of the state healthcare system of the Russian Federation considering cost data for 2022 in the population of women with infertility and poor ovarian response who are undergoing treatment with the use of assisted reproductive technologies (ART).Material and methods. Clinical and economic evaluation of follitropin alfa use in patients with infertility and poor ovarian response was performed by a cost minimization method, using data from the Uniform Information System for Procurement for the period from July to December 2022 inclusive. The budget impact analysis model compared the costs required for ovarian stimulation of patients with poor ovarian response receiving only a fixed dose combination (FDC) of follitropin alfa + lutropin alfa with the expected practice of switching 25% of these patients to follit...
Relevance. Combined foci of zoonotic infections are found in all regions of the Russian Federatio... more Relevance. Combined foci of zoonotic infections are found in all regions of the Russian Federation. A feature of combined foci is the common biocenosis for populations of pathogens of various etiologies (bacteria, viruses, parasitic infections) and the formation of natural foci by them. Aim. Epizootological study of the territory in the south of the Arkhangelsk region for the presence of combined foci of zoonotic infections (tularemia, leptospirosis and hemorrhagic fever with renal syndrome – HFRS). Materials and methods. 135 small mammals were captured and examined in the Ustyansky district of the Arkhangelsk region. Established the species composition and mixed infection among small mammals pathogens of tularemia, leptospirosis, hemorrhagic fever with renal syndrome. Results. In the south of the Arkhangelsk Region in the Ustyansky District, in 2019, for the first time, a combined natural focus of the forest type was identified and characterized. The bank vole and the common shrew ...
Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination... more Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by obvious shortage in supply of licensed vaccines. Development of new vaccines that are easy to manufacture and administer is highly desirable to overcome hurdles in vaccine scaling up and distribution, especially in developing countries. In the effort to satisfy vaccine demands we developed a new single dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein – “Sputnik Light”. Methods: We conducted an open label, two-stage, prospective, non-randomized phase I-II trial aimed to assess safety, tolerability and immunogenicity of “Sputnik Light” vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-Cov2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). The trial is registered at ClinicalTrials.gov (NCT04713488). Findings: Between January 14 and 27, 2021, 150 participants were screened, of whom 110 were enrolled. Most of solicited adverse reactions were mild (66.4% from all vaccinees), few were moderate (5.5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-Cov2 antibodies revealed group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data according to pre-existing immunity to SARS-Cov2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (GMT) 594.4 at a baseline up to 26899 comparing to 29.09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time in seropositive group seroconversion rate by day 42 was 92.9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81.7% (76/93) and 92.9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15.18 and 579.7 in the seronegative and seropositive groups, respectively. Each test to assess cell-mediated immune reactions was carried out on a separate group of 30 volunteers on day 10 upon vaccination. Antigen-specific T cell proliferation, formation of IFNy-producing cells, as well as IFNy secretion were detected in 96.7% (26/27), 96% (24/25) and 96% (24/25) seronegative and in 100% (3/3) 100% (5/5) and 100% (5/5) seropositive vaccinees, correspondingly. Interpretation: The single dose rAd26 vector-based COVID-19 vaccine “Sputnik Light” has a good safety profile and induced strong humoral and cellular immune responses both in seronegative and seropositive participants. Further investigation is needed to assess the effectiveness of this vaccine against COVID-19 used for primary and secondary vaccination. Clinical Trial Registration Details: The trial is registered at ClinicalTrials.gov (NCT04713488). Funding Information: Russian Direct Investment Fund. Declaration of Interests: OVZ, TAO, IVD, OP, DVS, DMG, ASD, AIT, DNS, IBE, EAT, AGB, ASE, FMI, NAN, NLL, ASS, SVB, BSN, DYL, ALG report patents for an immunobiological expression vector, pharmaceutical agent, and its method of use to prevent COVID-19. All other authors declare no competing interests. Ethics Approval Statement: The trial was approved by the local ethic committee and was conducted with the approval of the Ministry of Health of Russian Federation in compliance with International Conference on Harmonization and National Good Clinical Practice guidelines and Declaration of Helsinki.
The influence of both, the composite material based on the protein-mineral components including t... more The influence of both, the composite material based on the protein-mineral components including the prolonged form of the recombinant human bone morphogenetic protein 2 (rhBMP-2) and the method of the titanium implant's surface treatment, on the reparative osteogenesis and adhesion strength of the bone tissue – implant's surface contact was evaluated. Covering of implants with the composite coating promotes significant acceleration of the bone tissue regeneration processes in the site of implants loading. The composition coating with prolonged form of the rhBMP-2 promoted increasing of the neogenic bone tissue's adhesion with the implants, as compared with the coating without recombinant human bone morphogenetic protein. The implants treated with microarc oxidation demonstrated higher values of the breakout force during the separation of the implants from the bone than the implants treated with sandblasting method.
Семихин Александр Сергеевич – канд. биол. наук, ст. науч. сотр.,Котнова Алина Петровна – канд. хи... more Семихин Александр Сергеевич – канд. биол. наук, ст. науч. сотр.,Котнова Алина Петровна – канд. хим. наук, науч. сотр.,Башкиров Виктор Николаевич – канд. биол. наук, ст. науч. сотр., e-mail: [email protected],Карягина-Жулина Анна Станиславовна – д-р биол. наук, гл. науч. сотр., e-mail: akaryagina@ gmail.com,Лунин Владимир Глебович – д-р биол. наук, зав. лаб., e-mail: [email protected],Гинцбург Александр Леонидович – акад. РАМН, д-р биол. наук, проф., дир.Институт инженерной иммунологииКуликова Наталья Леонидовна – ст. науч. сотр.,Хлебников Валентин Сергеевич – д-р биол. наук, проф., зав. лаб.,Центральный НИИ туберкулеза РАМНКондратьева Татьяна Константиновна – д-р биол. наук, вед. науч. сотр.,Апт Александр Соломонович – д-р биол. наук, проф., зав. лаб.,НИИ Фхб им. А.Н. белозерского МГУВеселов Андрей Михайлович – аспирант.
Background While the world is experiencing another wave of COVID-19 pandemic, global vaccination ... more Background While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by an evident shortage in the supply of licensed vaccines. In an effort to satisfy vaccine demands we developed a new single-dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein – “Sputnik Light”. Methods We conducted an open label, prospective, non-randomised phase 1/2 trial aimed to assess safety, tolerability, and immunogenicity of “Sputnik Light” vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-CoV-2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). Findings Most of the solicited adverse reactions were mild (66·4% from all vaccinees), few were moderate (5·5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-CoV-2 antibodies revealed a group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data based on pre-existing immunity to SARS-CoV-2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (GMT) 594·4 at a baseline up to 26899 comparing to 29·09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time, in the seropositive group, seroconversion rate by day 42 was 92·9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81·7% (76/93) and 92·9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15·18 and 579·7 in the seronegative and seropositive groups, respectively. Antigen-specific T cell proliferation, formation of IFNy-producing cells, and IFNy secretion were observed in 96·7% (26/27), 96% (24/25), and 96% (24/25) of the seronegative group respectively and in 100% (3/3), 100% (5/5), and 100% (5/5) of the seropositive vaccinees, respectively. Interpretation The single-dose rAd26 vector-based COVID-19 vaccine “Sputnik Light” has a good safety profile and induces a strong humoral and cellular immune responses both in seronegative and seropositive participants. Funding Russian Direct Investment Fund.
ObjectivesVaccination remains the most effective response to the COVID-19 pandemic. Most vaccines... more ObjectivesVaccination remains the most effective response to the COVID-19 pandemic. Most vaccines use two-dose regimens. In turn, single-dose vaccines also have high potential, since, on the one hand, they simplify the vaccination program, make it more accessible and convenient for more people around the world, and on the other hand, they are better suited for subsequent revaccination. However, there is not enough data on the effectiveness of single-dose vaccine variants against new genetic lines to assess their current potential. It is not clear how much a single dose of immunization protects against the globally dominant delta variant. In this work, we investigated the effectiveness of a single dose vaccine (Sputnik Light, the first component of Sputnik V vaccine) against the Delta variant in Moscow.MethodsTo assess the effectiveness of one dose of viral vector vaccine based on rAd26 against the delta variant in Moscow, we used data from the Moscow registries of vaccination agains...
BACKGROUND Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunog... more BACKGROUND Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4·5 h after symptom onset. METHODS We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0-1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. FINDINGS Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89-89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1·47, 95% CI 0·93 to 2·32; p=0·10). The difference in the rate of favourable outcome at day 90 was 9·5% (95% CI -1·7 to 20·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0·044). INTERPRETATION Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. FUNDING The Russian Academy of Sciences.
Molekuliarnaia genetika, mikrobiologiia i virusologiia, 2012
Protein genes Ag85A, Esat-6, and Cfp10 of Mycobacterium tuberculosis were sequenced using the dat... more Protein genes Ag85A, Esat-6, and Cfp10 of Mycobacterium tuberculosis were sequenced using the database GenBank to implement selection and synthesis of primer pairs of given genes. PCR was used to obtain target amplicons of the genes. Chromosome DNA of M. tuberculosis H37Rv was used as the DNA amplification matrix. The PCR products were obtained using the plasmid pQE6, cloned, and amplified in the Escherichia coli M15 strain. Chimere products containing mycobacterial genes and cellulose binding protein domain (CBD), were obtained using the plasmid treated with restriction endonucleases. CBD fragment obtained using similar treatment of the ptt10 plasmid. The plasmids containing merged sequences of mycobacterial genes-antigenes and CBD were selected. The 3 mycobacterial genes were expressed in the E. coli M15 cells resulting in biosynthesis of corresponding recombinant proteins of expected molecular weight. Concentration of CBD, Cfp10-CBD, Ag85A-CBD, and ESAT6-CBD was 20%, 15%, and 15%...
Molekuliarnaia genetika, mikrobiologiia i virusologiia, 2009
Fusion gene consisting of dextran-binding domain from Leuconostoc mesenteroides subsp. Mesenteroi... more Fusion gene consisting of dextran-binding domain from Leuconostoc mesenteroides subsp. Mesenteroides (DBD) and human recombinant interferon-beta (IFN-beta) incorporated between the nucleotide sequence encoding for the recognition site of human enteropeptidase (DDDDK) was installed and constructed in Escherichia coli. The overproducing strain of the chimeric protein DBD-IFN-beta consisting of the IFN-beta, spacer including 10 GS-repeats, human enteropeptidase recognition site, and dextran-binding domain from Leuconostoc mesenteroides was constructed. Free human recombinant interferon-beta was obtained as a result of treatment of the chimeric protein DBD-IFN-beta immobilized on sephadex G-25 with human enteropeptidase. The ability of free and immobilized protein to protect human cells from viral infection was demonstrated. The developed approach can be used for purification of the recombinant proteins with different biological activity and possible construction of new immunostimulatin...
Bone morphogenetic protein-2 (rhBMP-2) represents the osteoinductive protein factor which plays a... more Bone morphogenetic protein-2 (rhBMP-2) represents the osteoinductive protein factor which plays a dominant role in growth and regeneration of a bone tissue. In clinical practice the bone grafting materials on the basis of rhBMP-2 are widely applied; the Russian analogues of similar materials are not produced. The fragment of the bmp2gene coding for a mature protein was cloned in Escherichia coli. The effective overproducing strain of rhBMP-2 was created on a basis of the E. coli BL21 (DE3). The rhBMP-2 production was about 25% of total cell protein. The biologically active dimeric form of rhBMP-2 was obtained by isolation and purification of protein from inclusion bodies with subsequent refolding. The rhBMP-2 sample with more than 80% of the dimeric form was obtained, which is able to interact with specific antibodies to BMP-2. Biological activity of the received rhBMP-2 samples was shown in the in vitro experiments by induction of alkaline phosphatase synthesis in C2C12 and C3H10T1/2 cell cultures. On model of the ectopic osteogenesis it was shown that received rhBMP-2 possesses biological activity in vivo, causing tissue calcification in the place of an injection. The protein activity in vivo depends on way of protein introduction and characteristics of protein sample: rhBMP-2 may be introduced in an acid or basic buffer solution, with or without the carrier. The offered method of rhBMP-2 isolation and purification results in increasing common protein yield as well as the maintenance of biologically active dimeric form in comparison with the analogues described in the literature.
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Papers by A. Semikhin