Прогноз в области создания вакцин нового поколения для вакцинопрофилактики и вакцинотерапии инфекционных и неинфекционных болезней

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rAAV expressing recombinant antibody for emergency prevention and long-term prophylaxis of COVID-19

IntroductionNumerous agents for prophylaxis of SARS-CoV-2-induced diseases are currently registered for the clinical use. Formation of the immunity happens within several weeks following vaccine administration which is their key disadvantage. In contrast, drugs based on monoclonal antibodies, enable rapid passive immunization and therefore can be used for emergency pre- and post-exposure prophylaxis of COVID-19. However rapid elimination of antibody-based drugs from the circulation limits their usage for prolonged pre-exposure prophylaxis.MethodsIn current work we developed a recombinant adeno-associated viral vector (rAAV), expressing a SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibody P2C5 fused with a human IgG1 Fc fragment (P2C5-Fc) using methods of molecular biotechnology and bioprocessing.Results and discussionsA P2C5-Fc antibody expressed by a proposed rAAV (rAAV-P2C5-Fc) was shown to circulate within more than 300 days in blood of transduced mice and protect animals from lethal SARS-CoV-2 virus (B.1.1.1 and Omicron BA.5 variants) lethal dose of 105 TCID50. In addition, rAAV-P2C5-Fc demonstrated 100% protective activity as emergency prevention and long-term prophylaxis, respectively. It was also demonstrated that high titers of neutralizing antibodies to the SARS-CoV-2 virus were detected in the blood serum of animals that received rAAV-P2C5-Fc for more than 10 months from the moment of administration.Our data therefore indicate applicability of an rAAV for passive immunization and induction of a rapid long-term protection against various SARS-CoV-2 variants

ВОЗМОЖНО ЛИ ВЛИЯНИЕ МИКОПЛАЗМЕННОЙ ИНФЕКЦИИ НА ПАТОГЕНЕЗ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ?

Objective: to define a possible correlation between Mycoplasma infection persistence and prostate cancer (PC). Subjects and methods. Two hundred and fifty males aged 45 to 83 years (mean age 65.50.71 years) with suspected PC were examined. In all the patients, polyfocal prostate biopsy from 12 points was carried out, by additionally taking 2 tissue columns from the peripheral area of both lobes. The basic material was referred for morphological study; the two additional columns were tested for Mycoplasma DNA by a polymerase chain reaction (PCR) and real-time PCR. The study was blind. According to the morphological findings, the patients were divided into 2 groups: 1) those with chronic prostatitis, prostate adenoma, low-grade prostatic interstitial neoplasia (PIN); 2) those with high-grade PIN (HG-PIN), PC. There were no age differences between the groups (p = 0.05). Results. The standard procedure for PCR was applied to 127 subjects. Twenty-six (20.5%) of the 127 subjects with suspected PC were found to have Mycoplasma infection, Mycoplasma being detected in 21 (26.2%) of the 81 patients with verified HG-PIN and PC. Mycoplasma hominis was encountered in 19 (15%) patients of the 127 subjects with suspected PC and this infection was present in 16 (20%) of the 81 patients with verified HG-PIN and PC. Comparison of the frequency of HG-PIN and PC in the patients of general group (60%) and in those with Mycoplasma infection (80.8%) revealed significant differences (p = 0.031). HG-PIN and PC were also significantly more frequently seen in the patients with Mycoplasma hominis (84.2%) that in the general patient group (60%) (p = 0.033). There were no significant differences in the frequency of HG-PIN and PC between the patients from the general group (60%) and those with Mycoplasma genitalium (71.4%) (p = 0.05). The patients with verified PC and HG-PIN were more frequently found to have Mycoplasma hominis (20%) than Mycoplasma genitalium (6.2%), which further drew our closer attention to just this pathogen. The real-time PCR was used in 123 subjects to detect Mycoplasma. HG-PIN and prostate adenocarcinoma were revealed in 63 of the 123 patients with suspected PC, Mycoplasma hominis was seen in 46 (37%). The frequency (n=46) was 73.9%. The frequency of HG-PIN and PC was significantly higher in the patients with isolated Mycoplasma hominis DNA that in those without this pathogen (p < 0.001). Conclusion. Thus, the investigation showed a significantly higher correlation in the frequency of HG-PIN and PC in the patients with Mycoplasma infection that in the general study patients with suspected PC. This was supported by the use of both the standard procedure for Mycoplasma DNA determination and real-time PCR diagnosis.Objective: to define a possible correlation between Mycoplasma infection persistence and prostate cancer (PC). Subjects and methods. Two hundred and fifty males aged 45 to 83 years (mean age 65.50.71 years) with suspected PC were examined. In all the patients, polyfocal prostate biopsy from 12 points was carried out, by additionally taking 2 tissue columns from the peripheral area of both lobes. The basic material was referred for morphological study; the two additional columns were tested for Mycoplasma DNA by a polymerase chain reaction (PCR) and real-time PCR. The study was blind. According to the morphological findings, the patients were divided into 2 groups: 1) those with chronic prostatitis, prostate adenoma, low-grade prostatic interstitial neoplasia (PIN); 2) those with high-grade PIN (HG-PIN), PC. There were no age differences between the groups (p = 0.05). Results. The standard procedure for PCR was applied to 127 subjects. Twenty-six (20.5%) of the 127 subjects with suspected PC were found to have Mycoplasma infection, Mycoplasma being detected in 21 (26.2%) of the 81 patients with verified HG-PIN and PC. Mycoplasma hominis was encountered in 19 (15%) patients of the 127 subjects with suspected PC and this infection was present in 16 (20%) of the 81 patients with verified HG-PIN and PC. Comparison of the frequency of HG-PIN and PC in the patients of general group (60%) and in those with Mycoplasma infection (80.8%) revealed significant differences (p = 0.031). HG-PIN and PC were also significantly more frequently seen in the patients with Mycoplasma hominis (84.2%) that in the general patient group (60%) (p = 0.033). There were no significant differences in the frequency of HG-PIN and PC between the patients from the general group (60%) and those with Mycoplasma genitalium (71.4%) (p = 0.05). The patients with verified PC and HG-PIN were more frequently found to have Mycoplasma hominis (20%) than Mycoplasma genitalium (6.2%), which further drew our closer attention to just this pathogen. The real-time PCR was used in 123 subjects to detect Mycoplasma. HG-PIN and prostate adenocarcinoma were revealed in 63 of the 123 patients with suspected PC, Mycoplasma hominis was seen in 46 (37%). The frequency (n=46) was 73.9%. The frequency of HG-PIN and PC was significantly higher in the patients with isolated Mycoplasma hominis DNA that in those without this pathogen (p < 0.001). Conclusion. Thus, the investigation showed a significantly higher correlation in the frequency of HG-PIN and PC in the patients with Mycoplasma infection that in the general study patients with suspected PC. This was supported by the use of both the standard procedure for Mycoplasma DNA determination and real-time PCR diagnosis

Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study

To protect young individuals against SARS-CoV-2 infection, we conducted an open-label, prospective, non-randomised dose-escalation Phase 1/2 clinical trial to evaluate the immunogenicity and safety of the prime-boost “Sputnik V” vaccine administered at 1/10 and 1/5 doses to adolescents aged 12–17 years. The study began with the vaccination of the older cohort (15-to-17-year-old participants) with the lower (1/10) dose of vaccine and then expanded to the whole group (12-to-17-year-old participants). Next, 1/5 dose was used according to the same scheme. Both doses were well tolerated by all age groups. No serious or severe adverse events were detected. Most of the solicited adverse reactions were mild. No significant differences in total frequencies of adverse events were registered between low and high doses in age-pooled groups (69.6% versus 66.7%). In contrast, the 1/5 dose induced significantly higher humoral and T cell-mediated immune responses than the 1/10 dose. The 1/5 vaccine dose elicited higher antigen-binding (both S and RBD-specific) as well as virus-neutralising antibody titres at the maximum of response (day 42), also resulting in a statistically significant difference at a distanced timepoint (day 180) compared to the 1/10 vaccine dose. Higher dose resulted in increased cross-neutralization of Delta and Omicron variants.;Clinical Trial RegistrationClinicalTrials.gov, NCT04954092, LP-007632

Analysis of the genome of type 7 simian adenovirus using restrictases.

The effect of the restricting endonucleases R.EcoRI, R.BamI and R.SalI on the genome of type 7 simian adenovirus (SA-7) has been studied. Since the DNA has only one site of R.EcoRI recognition the enzyme cleaves SA-7 DNA into two fragments with the molecular weights 12.0 and 10.0 . 10(6). The restrictase R.BamI cleaves the SA-7 DNA at six sites producing 7 fragments with the molecular weights 6.6, 5.9, 3.8, 2.7, 1.3, 0.7 and 0.6 . 10(6). R.SalI cleavage yields 6 fragments with the molecular weights 8.1, 5.5, 4.3, 2.45, 1.2 and 0.6 . 10(6). The R.BamI and R.SalI fragments are arranged in the orders E-A-D-F-C-G-B and A-B-D-F-E-C, respectively. The only R.EcoRI recognition site is localized in the C fragment produced by R.BamI and in the B fragment produced by R.SalI

INFLUENCE OF S. TYPHI LIPOPOLISACCHARIDE UPON EPITHELIZATION OF SKIN WOUNDS AND EPIDERMAL GROWTH FACTOR SECRETION

Abstract. Influence of topical application of bacterial lipopolysaccharide (LPS), a Toll-like receptor 4 agonist, upon epithelization process was investigated, using a murine incisional skin wound model. It was shown that topical LPS application accelerates wound epithelization, and this process was associated with increased levels of epidermal growth factor secretion in wounded skin area

Biological activity of the intact and cleaved DNA of the simian adenovirus 7.

Only the deproteinized DNA preparations of the simian adenovirus of the type 7 (SA 7) exhibited transforming and tumorigenic activity. The complex of the SA7 DNA with terminal protein (TP) did not exhibit either transforming or tumorigenic activity in cell cultures. In contrast to the transforming potential the infectious titers of the DNA - TP complex for the monkey kidney cells were 30-50 times higher than those of pure DNA. Cleavage of the SA7 DNA by specific endonucleases enhanced the tumorigenic potential of pure DNA, suppressed its infectivity and did not affect the lack of transformation capacity of the DNA - TP complex. The onc-gene was localized in the left terminal fragment with the minimal size 4,3x10(6)D in the case of R.Sal I. The tumorigenic activity was found to decrease with an increase in the size of the DNA fragment containing the onc-gene