The aim. Study of pharmacodynamic parameters and confirmation of pharmacodynamic equivalence (bioequivalence) of the drugs Antareit® (INN: magaldrate), chewable tablets, 800 mg (Valenta Pharm JSC, Russia) and Riopan (INN magaldrate), chewable tablets, 800 mg (Takeda GmbH, Germany). Material and methods. An open randomized crossover study was conducted to investigate the pharmacodynamics of the study drug Antareit® and the reference drug Riopan, assessing their bioequivalence after taking 2 chewable tablets of the study or reference drug 3 times a day. The study involved 40 healthy volunteers who were randomized into 2 groups of 20 people depending on the sequence of drug administration in study periods I and II. Intragastric acidity was measured with a pH-probe within 30 minutes before and for one hour after taking the study drugs. Based on the data obtained, 90% confidence intervals (CI) were calculated for the pharmacodynamic parameter AUCABL, reflecting the area above the baseline pH. The safety of the study drugs was assessed by the frequency and severity of adverse events (AEs). Results. Statistical analysis showed that the 90% CI for the ratio of the mean values of the AUC ABL parameter of the study drug to the reference drug did not fall below 80% (90% CI: 80.55–119.49). During the study, 18 adverse events (AEs) were reported in 15.4% (6 of 39) of volunteers in the safety population, and there were no statistically significant differences in the incidence of AEs between groups, nor in the incidence of AEs depending on the drug taken. Conclusion. The studied drugs are pharmacodynamically equivalent and have a similar safety profile when administered repeatedly.

In order to combat resistance, it is necessary to develop antimicrobial agents that act differently from conventional antibiotics. Fluorothiazinone, 300 mg tablet (The Gamaleya National Research Center), is an original antibacterial drug based on a new small molecule T3SS and flagellum inhibitor. A total of 357 patients with complicated urinary tract infections (UTIs) were divided into two groups and given Fluorothiazinone 1200 mg/day or a placebo for 7 days to evaluate the efficacy and safety of the drug. Additionally, all patients were given Cefepime 2000 mg/day. Fluorothiazinone with Cefepime showed superiority over placebo/Cefepime based on the assessment of the proportion of patients with an overall outcome in the form of a cure after 21 days post-therapy (primary outcome), overall outcome in cure rates, clinical cure rates, and microbiological efficacy at the end of therapy and after 21 days post-therapy (secondary outcomes). In patients who received Fluorothiazinone, the rate of infection recurrences 53 and 83 days after the end of the therapy was lower by 18.9%, compared with patients who received placebo. Fluorothiazinone demonstrated a favorable safety profile with no serious unexpected adverse events reported. The results showed superiority of the therapy with Fluorothiazinone in combination with Cefepime compared with placebo/Cefepime in patients with cUTIs.

We have developed Convacell®—a COVID-19 vaccine based on the recombinant nucleocapsid (N) protein of SARS-CoV-2. This paper details Convacell’s® combined phase I/II and IIb randomized, double-blind, interventional clinical trials. The primary endpoints were the frequency of adverse effects (AEs) and the titers of specific anti-N IgGs induced by the vaccination; secondary endpoints included the nature of the immune response. Convacell® demonstrated high safety in phase I with no severe AEs detected, 100% seroconversion by day 42 and high and sustained for 350 days anti-N IgG levels in phase II. Convacell® also demonstrated a fused cellular and humoral immune response. Phase IIb results showed significant post-vaccination increases in circulating anti-N IgG and N protein-specific IFNγ+-producing PBMC quantities among 438 volunteers. Convacell® showed same level of immunological efficacy for single and double dose vaccination regimens, including for elderly patients. The clinical studies indicate that Convacell® is safe and highly immunogenic.

All antipsychotics currently used in clinic block D2 dopamine receptors. Trace amine-associated receptor 1 is emerging as a new therapeutic target for schizophrenia and several other neuropsychiatric disorders. SEP-363856 (International Nonproprietary Name: Ulotaront) is an investigational antipsychotic drug with a novel mechanism of action that does not involve antagonism of dopamine D2 receptors. Ulotaront is an agonist of trace amine-associated receptor 1 and serotonin 5-HT1A receptors, but can modulate dopamine neurotransmission indirectly. In 2019, the United States Food and Drug Administration granted Breakthrough Therapy Designation for ulotaront for the treatment of schizophrenia. Phase 2 clinical studies indicated that ulotaront can reduce both positive and negative symptoms of schizophrenia without causing the extrapyramidal or metabolic side effects that are inherent to most currently used antipsychotics. At present, it is in phase 3 clinical development for the treatment of schizophrenia and is expected to be introduced into clinical practice in 2023–2024. Clinical studies evaluating the potential efficacy of ulotaront in Parkinson’s disease psychosis, generalized anxiety disorder, and major depressive disorder have also been started. The aim of this scoping review is to summarize all currently available preclinical and clinical evidence on the utility of ulotaront in the treatment of schizophrenia. Here, we show the main characteristics and distinctive features of this drug. Perspectives and limitations on the potential use of ulotaront in the pharmacotherapy of several other neuropsychiatric disorders are also discussed.

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.

Starting from a screening hit, a set of analogs was synthesized based on a 4-(2-aminoethyl)piperidine core not associated previously with trace amine-associated receptor 1 (TAAR1) modulation in the literature. Several structure–activity relationship generalizations have been drawn from the observed data, some of which were corroborated by molecular modeling against the crystal structure of TAAR1. The four most active compounds (EC50 for TAAR1 agonistic activity ranging from 0.033 to 0.112 μM) were nominated for evaluation in vivo. The dopamine transporter knockout (DAT-KO) rat model of dopamine-dependent hyperlocomotion was used to evaluate compounds’ efficacy in vivo. Out of four compounds, only one compound (AP163) displayed a statistically significant and dose-dependent reduction in hyperlocomotion in DAT-KO rats. As such, compound AP163 represents a viable lead for further preclinical characterization as a potential novel treatment option for disorders associated with increased dopaminergic function, such as schizophrenia.

ABSTRACTWe present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in adult volunteers aged 18-60.Safety of the vaccine was assessed in 398 volunteers who received two doses of the vaccine (n=298) or placebo (n=100). The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AE), or other significant AE related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p<0.05).Immunogenicity assessment was performed in 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.At Day 42 after the first immunization the seroconversion rate in participants who were seronegative at screening was 86.9% with average the geometric mean neutralizing antibody (nAB) titer of 1:20. Statistically significant (p<0.05) increase of IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the first immunization.In participants who were seropositive at screening but had nAB titers below 1:256 the rate of 4-fold increase in nAB levels was 85.2%, while in the participants with nAB titers >1:256 the rate of 4-fold increase in nAB levels was below 45%. For the participants who were seropositive at screening the second immunization did not lead to a significant increase in nAB titers.In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with 86.9% seroconversion rates in participants, who were seronegative at screening. In participants who were seropositive at screening and had nAB titers below 1:256, a single immunization lead to a 4-fold increase in nAB levels in 85.2% cases.

A focused in-house library of about 1000 compounds comprising various heterocyclic motifs in combination with structural fragments similar to β-phenylethylamine or tyramine was screened for the agonistic activity towards trace amine-associated receptor 1 (TAAR1). The screening yielded two closely related hits displaying EC50 values in the upper submicromolar range. Extensive analog synthesis and testing for TAAR1 agonism in a BRET-based cellular assay identified compound 62 (LK00764) with EC50 = 4.0 nM. The compound demonstrated notable efficacy in such schizophrenia-related in vivo tests as MK-801-induced hyperactivity and spontaneous activity in rats, locomotor hyperactivity of dopamine transporter knockout (DAT-KO) rats, and stress-induced hyperthermia (i.p. administration). Further preclinical studies are necessary to evaluate efficacy, safety and tolerability of this potent TAAR1 agonist for the potential development of this compound as a new pharmacotherapy option for schizophrenia and other psychiatric disorders.

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.

Fludarabine is a purine antimetabolite with a pronounced immunosuppressive effect. The inhibitory effect of fludarabine depends on its concentration in blood plasma. In addition, the phenotypic characteristics of patients affect the pharmacokinetic and pharmacodynamic profile of the drug, which necessitates a personalized approach to the dosage regimen. The chromatography-mass spectrometric method for the quantitative determination of 2-fluorine in blood plasma was developed for studying the individual parameters of pharmacokinetics of the international non-proprietary name (INN) fludarabine in patients with B-cell chronic lymphocytic leukemia during the standard course. Such method for the quantitative determination of 2-fluorine in blood plasma was developed and validated in accordance with international requirements. Significant individual variability of the main pharmacokinetic parameters in patients with B-cell chronic lymphocytic leukemia with a single oral administration of the drug with INN fludarabine at a dose of 40 mg/m2 was established, so the coefficient of variability Cmax was 42 %, Tmax — 92 %, AUC0-t — 45 %, Kel — 23 %, T1/2 — 26 %. It should be noted that there is a high interindividual variability of fludarabine, for example, 24 hours after taking the study drug, the maximum and minimum plasma concentrations of the fludarabine metabolite 2-fluoro-ara-A in different in patients with B-cell chronic lymphocytic leukemia differed 9 times. Individual variability of pharmacokinetic parameters characterizing absorption (Cmax/AUC0-t) and total clearance of the active metabolite of fludarabine is statistically significantly associated with a combination of gender and anthropometric factors.

A high demand for sildenafil-based drugs puts a premium on the development of methods for quantitation of sildenafil in bio-substrates to facilitate pharmacokinetic analysis in bioequivalence studies. High performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was proposed for the method development due to its high sensitivity, selectivity, reproducibility, and performance. The aim of the study was to develop and validate an HPLC-MS/MS method for quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma. Approbation of the developed technique in the study of the pharmacokinetic profiles of sildenafil and N-desmethyl sildenafil in healthy volunteers in the study of the bioequivalence of the drug sildenafil in the form of a spray. Materials and methods: the method was implemented using the Agilent 1200 high-performance liquid chromatography system with the Agilent 6440 triple quadrupole system, and Poroshell 120 EC-C18 chromatographic column, 4.6 m × 150 mm × 2.7 μm. Calibration samples were prepared using sildenafil citrate and N-desmethyl sildenafil reference standards with 99.5 and 98.5% purity, respectively. Vardenafil was used as an internal standard. Pharmacokinetic profiles of sildenafil and N-desmethyl sildenafil were studied in 44 healthy male volunteers as part of a bioequivalence study approved by the Ministry of Health of the Russian Federation. The primary data processing was performed using Mass Hunter software version B 06.00, and statistical processing was performed using Microsoft Office Excel 2010 and Statistica 6.1. Results: the authors developed and validated a method for quantitation of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma. The developed method was used successfully to study pharmacokinetic profiles of the discussed compounds in healthy volunteers. Conclusions: the developed method of quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma is simple, reproducible, fast, and robust. The results of the pharmacokinetic studies using the developed method demonstrated bioequivalence of the test product and the reference product.

A high demand for sildenafil-based drugs puts a premium on the development of methods for quantitation of sildenafil in bio-substrates to facilitate pharmacokinetic analysis in bioequivalence studies. High performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was proposed for the method development due to its high sensitivity, selectivity, reproducibility, and performance. The aim of the study was to develop and validate an HPLC-MS/MS method for quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma. Approbation of the developed technique in the study of the pharmacokinetic profiles of sildenafil and N-desmethyl sildenafil in healthy volunteers in the study of the bioequivalence of the drug sildenafil in the form of a spray. Materials and methods : the method was implemented using the Agilent 1200 high-performance liquid chromatography system with the Agilent 6440 triple quadrupole system, and Poroshell 120 EC-C18 chromatographic column, 4.6 m × 150 mm × 2.7 μm. Calibration samples were prepared using sildenafil citrate and N-desmethyl sildenafil reference standards with 99.5 and 98.5% purity, respectively. Vardenafil was used as an internal standard. Pharmacokinetic profiles of sildenafil and N-desmethyl sildenafil were studied in 44 healthy male volunteers as part of a bioequivalence study approved by the Ministry of Health of the Russian Federation. The primary data processing was performed using Mass Hunter software version B 06.00, and statistical processing was performed using Microsoft Office Excel 2010 and Statistica 6.1. Results : the authors developed and validated a method for quantitation of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma. The developed method was used successfully to study pharmacokinetic profiles of the discussed compounds in healthy volunteers. Conclusions : the developed method of quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma is simple, reproducible, fast, and robust. The results of the pharmacokinetic studies using the developed method demonstrated bioequivalence of the test product and the reference product.

AIM:In order to evaluate the bioequivalence and benefits of a new dosage form of the type 5 phosphodiesterase inhibitor, sildenafil, two open-label studies in healthy male volunteers were carried out.MATERIALS AND METHODS:An open, randomized, crossover study to compare the pharmacokinetics after a single dose of sildenafil at a dosage of 50 mg on an empty stomach in a new spray form (test drug) and in a traditional tablet form (comparison drug) on 44 volunteers (18 to 43 years old) was done. To assess the effect of food intake on pharmacokinetics, an open, non-randomized study was conducted on 6 healthy male volunteers (from 23 to 35 years old) who received sildenafil (50 mg) after a meal in timely fashion: 1) spray, under the tongue, without drinking, 2) spray , in the mouth, drinking water and 3) the tablet form, drinking water. For pharmacokinetic analysis, blood was analyzed for 24 hours. Plasma concentration of sildenafil was determined by high performance liquid chromatography with tandem mass spectrometric detection (HPLC/TM/SD). The main parameters were the rate (maximum concentration; Cmax) and the degree of absorption (area under the pharmacokinetic curve "concentration-time" during the observation period; AUC0-t) after a single dose of drugs. In addition, the pharmacokinetic profiles of the bioavailability of sildenafil and its active metabolite, N-desmethyl sildenafil, as well as the safety of the different dosage forms, were evaluated.RESULTS:When comparing taking drugs on an empty stomach, the 90% confidence intervals (CI) of the ratios of the mean Cmax and AUC0-t values of sildenafil were 82-106% and 82-101%, respectively. An earlier achievement of the maximum concentration of sildenafil was detected when taking the test drug compared with the standard form (51 and 62 minutes, respectively, Z-value=-2.25, p-value=0.0244). In addition, it was shown that when taking Viagra after a meal, the determination of sildenafil in plasma was delayed (after 30 minutes) compared to the tested drugs (after 10 minutes), however, significant differences in Tmax between the dosage forms were not seen. In two studies, most adverse events were mild to moderate and resolved uneventfully.DISCUSSION:The bioavailability of the new dosage form, the sildenafil spray, is equivalent to the traditional form, however, it has an advantage in terms of onset of action. For example, when taking a spray, an earlier achievement of the maximum concentration of sildenafil and an earlier detection of sildenafil in plasma are shown compared to the traditional tablet form.CONCLUSIONS:Our results suggest that the new dosage form of sildenafil is a reliable alternative therapeutic option for the treatment of erectile dysfunction.

Study aims: The study purpose was to analyze the results of the clinical and laboratory monitoring of HBeAg-negative chronic hepatitis B patients after discontinuation of longterm nucleosides analogues antiviral therapy in order to determine further management.Materials and methods: A retrospective-prospective investigation was performed in 106 patients with diagnosis of HBeAg-negative chronic hepatitis B during the course of antiviral therapy using nucleosides analogues. Average treatment duration was 190,1±77,7 weeks. The therapy was discontinued for 29 patients in the period of time from two to five years of the treatment, they were followed up from 6 months to 6 years. The activity of aminotransferases, the levels of HBV DNA were evaluated, the liver elastometry was performed during the patients monitoring. The relapse of disease after the treatment discontinuation was considered when the viral load exceeded 2.0x103 IU / ml and/or alanine aminotransferase levels were above the reference values.Results:The viral load varied from 4,0х102 IU/ml to 2,87 х 107 IU/ml at 86,2% cases after the 6 months of discontinuation of the treatment. However median levels of viral load were not higher than 2,5 х 103 IU/ml at different timepoints of observation. The VL was higher than 2,0 х 103 IU/ml in 62,1% patients and it matched to relapse criterion. Clinical relapse was not revealed in 13,8% cases at observational period from 6 months to 2 years. The second course of antiviral therapy was not required for 37,9% patients, at the same time it was necessary to consider it for the rest ones.Conclusion: Regular medical checkups with periodical clinical, laboratory and instrumental examinations after antiviral treatment discontinuation are required for timely detection of relapse and decision regarding the next course of antiviral therapy.

Currently, second-generation hepatitis B vaccines are widely used. They are produced in biotechnological eukaryotic yeast-based systems and contain the S-protein domain of HBsAg particle in the complete absence of pre-S1 and pre-S2 domains. At the same time, these antigens were proved to significantly influence immunogenicity, which makes the development and use of third-generation vaccines containing all antigenic determinants a long-range objective. A randomized, double-blind clinical study was conducted to compare immunogenicity of second- and third-generation vaccines Engerix-B™ and Sci-B-Vac™, respectively. Healthy subjects of both sexes aged 18 to 45 years (n = 94) who are seronegative for HBsAg, HBsAb, HBcAb at screening and who previously had not received immunobiological agents for hepatitis B prophylaxis were included in the study. Group I (n = 47) received the second-generation vaccine Engerix-B™, Group II (n = 47) — the third-generation vaccine Sci-B-Vac™. Subjects received vaccines three times — on days 1, 28 and 180 of the study. HBsAb levels, rates of seroconversion (the proportion of subjects with HBsAb levels > 2.1 mIU/mL) and seroprotection (the proportion of subjects with HBsAb levels ≥ 10 mIU/mL) were assessed on days 28, 90, 180 and 210 of the study. Early seroconversion rate assessed on Day 28 was 76.60% in Group I and 93.88% in Group II (p < 0.05); seroprotection rate was 51.06 and 61.22%, respectively. These differences in the proportion of subjects who achieved seroconversion on Day 28 may indicate a faster immunological response to Sci-B-Vac™ vaccine. Statistically significant differences between the level of antibodies on days 90 and 180 (p < 0.05) were observed when analyzing the average values of HBsAb concentration in Groups I and II. The concentration of HBsAb on Day 90 was 378.68±60.95 mIU/mL in Group I, and 618.31±58.34 mIU/mL in Group II. On Day 180, the concentration of HBsAb reached 441.34±63.83 mIU/mL in Group I, and 757.72±55.14 mIU/mL in Group II. The significance of dependence of antibody level on sex, age and body weight was analyzed. It was revealed that the age of a vaccinated subject affects antibody level after administration of Engerix-B™ (p < 0.05). The results obtained suggest that there is a rapid and strong immune response to the third-generation vaccine Sci-B-Vac™. This may indicate advantage of the vaccine containing all three recombinant proteins of hepatitis B virus envelope, which, in turn, can play a key role in clinical practice for urgent prophylaxis of hepatitis B, as well as for treatment of immunocompromised conditions.

Previously, we showed that CD206-targeted liposomal delivery of co-encapsulated immunodominant myelin basic protein (MBP) sequences MBP46–62, MBP124–139 and MBP147–170 (Xemys) suppressed experimental autoimmune encephalomyelitis in dark Agouti rats. The objective of this study was to assess the safety of Xemys in the treatment of patients with relapsing-remitting multiple sclerosis (MS) and secondary progressive MS, who failed to achieve a sustained response to first-line disease-modifying therapies. In this phase I, open-label, dose-escalating, proof-of-concept study, 20 patients with relapsing-remitting or secondary progressive MS received weekly subcutaneously injections with ascending doses of Xemys up to a total dose of 2.675 mg. Clinical examinations, including Expanded Disability Status Scale score, magnetic resonance imaging results, and serum cytokine concentrations, were assessed before the first injection and for up to 17 weeks after the final injection. Xemys was safe and well tolerated when administered for 6 weeks to a maximum single dose of 900 μg. Expanded Disability Status Scale scores and numbers of T2-weighted and new gadolinium-enhancing lesions on magnetic resonance imaging were statistically unchanged at study exit compared with baseline; nonetheless, the increase of number of active gadolinium-enhancing lesions on weeks 7 and 10 in comparison with baseline was statistically significant. During treatment, the serum concentrations of the cytokines monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and interleukin-7 decreased, whereas the level of tumor necrosis factor-α increased. These results provide evidence for the further development of Xemys as an antigen-specific, disease-modifying therapy for patients with MS.

HBsAg earlier was always considered as the required serological marker of the current HBV-infection, and the presence of НВsAb was considered as evidence of the previous infection with the elimination of virus and the recovery. Exceptions of this rule were discovered more than two decades ago, after which it appeared the concept «occult» hepatitis В. Aim: to characterize clinical course of chronic HBV-infection HBsAg-negative (occult) depending on HBsAb levels in serum. Materials and methods : were examined 198 patients with HBsAg-negative chronic HBV-infection, with the confirmation mono-infection in the absence of factors of liver injury noninfectious etiology. Results: most of the patient was in 45–74 years old. In 53 patients (27,8%) were identified HBcAb and HBsAb titer greater than 10 IU/l: positive HBcAb and HBsAb titre from 10 to 100 IU/l in 21,2% of cases; positive HBcAb and HBsAb titer more than 100 IU/l – 5,5%. DNA HBV was determined in 7,1% of cases. Cirrhotic stage of disease diagnosed in 30,2% of patients with low levels of HBsAb and 13,2% of patients with a high level of HBsAb. Evaluation of the degree of liver cirrhosis were revealed a class C in 86,9% of cases. Patients with decompensated cirrhosis are twice as likely HBsAb in low titre than high. Conclusion : chronic HBV-infection with the serological profile of «past infection» independently of the level HBsAb can estimate as disease with the latent flow and may progression of pathologic process up to cirrhosis of the liver. These patients are subject to regular medical check once a year in a day hospital of a specialized center.