Background The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, S and RBD from SARS-CoV-2 variants of concerns show considerable sequence variations and repeated injections for boosting specific immunity are necessary. Aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Methods Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The N protein vaccine was obtained by formulation of recombinant N as squalane-based emulsion and used to immunize Balb/c mice, NOD scid gamma (NSG) mice engrafted with human PBMC, rabbits and marmoset monkeys to study safety as well as antibody and cellular immunity using ELISA for antibodies, measurement of N-specific Th1 and Th2 cytokine secretion and carboxyfluorescein succinimidyl ester (CFSE) dilution assays for CD4 and CD8 T cell responses. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Results Immunization of mice, rabbits and Syrian hamsters with the recombinant N protein-based vaccine formulated as squalane-based emulsion (Convacell®) induced sustainable N-specific IgG responses and a N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys a N-specific CD4 as well as CD8 T cell response was observed. Vaccinated and then infected Syrian hamsters showed reduced lung histopathology, reduced virus was detected in lung tissue, lung weight relative to the body was not increased after challenge and body weight was regained faster than in non-vaccinated animals. Repeated dose toxicity studies in mice and rabbits showed that Convacell® was well tolerated and safe. Conclusions Convacell® induced a SARS-CoV-2-specific protective immune response in Syrian hamsters. It is a new vaccine targeting the nucleocapsid protein of SARS-CoV-2 and thus may augment the armamentarium of vaccines for COVID-19.
The second generation COVID-19 vaccines should produce the long-term protective immune response to the existing and novel strains of SARS-CoV-2. The Convacell® vaccine was designed to produce such immune response by using N protein as an antigen. N-protein is not susceptible to fast accumulation of mutations and is highly homologous to nucleocapsid proteins of other β-coronaviruses. The study was aimed to perform in vitro assessment of the Convacell® vaccine ability to produce immune response to the Wuhan, Delta, and Omicron strains. Mononuclear cells of vaccinated volunteers and survivors were subjected to N protein stimulation. After that specific activation of the cells was assessed by flow cytometry. The results showed that a sibstantial percentage of CD4 and CD8 cells produced IFNγ and IL2 in response to stimulation. No significant reduction of the response to strains Delta and Omicron compared to the Wuhan strain was revealed. The findings support the direction of the N protein based vaccine design towards creation of the universal vaccine.
Background Severe acute respiratory syndrome corona virus (SARS‐CoV‐2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety and efficacy of a SARS‐CoV‐2‐specific siRNA‐peptide dendrimer formulation MIR 19® (siR‐7‐EM/KK‐46) targeting a conserved sequence in known SARS‐CoV‐2 variants for treatment of COVID‐19. Methods We conducted an open‐label, randomized, controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled siR‐7‐EM/KK‐46 (3.7 mg and 11.1 mg/day: low and high dose, respectively) in comparison with standard etiotropic drug treatment (control group) in patients hospitalized with moderate COVID‐19 (N = 52 for each group). The primary endpoint was the time to clinical improvement according to predefined criteria within 14 days of randomization. Results Patients from the low‐dose group achieved the primary endpoint defined by simultaneous achievement of relief of fever, normalization of respiratory rate, reduction of coughing, and oxygen saturation of >95% for 48 h significantly earlier (median 6 days; 95% confidence interval [CI]: 5–7, HR 1.75, p = .0005) than patients from the control group (8 days; 95% CI: 7–10). No significant clinical efficacy was observed for the high‐dose group. Adverse events were reported in 26 (50.00%), 25 (48.08%), and 28 (53.85%) patients from the low‐, high‐dose and control group, respectively. None of them were associated with siR‐7‐EM/KK‐46. Conclusions siR‐7‐EM/KK‐46, a SARS‐CoV‐2‐specific siRNA‐peptide dendrimer formulation is safe, well tolerated and significantly reduces time to clinical improvement in patients hospitalized with moderate COVID‐19 compared to standard therapy in a randomized controlled trial.
1 ФГБОУ ВО «Пермский государственный медицинский университет им. академика Е.А. Вагнера» Минздрава России 2 ФГУП «Санкт-Петербургский НИИ вакцин и сывороток и предприятие по производству бактериальных препаратов» ФМБА России Оценка реактогенности, безопасности и иммуногенности отечественной гриппозной инактивированной расщепленной вакцины ФЛЮ-М при иммунизации взрослых в возрасте 18-60 лет Резюме В статье представлены результаты простого слепого рандомизированного плацебо-контролируемого одноцентрового проспективного исследования реактогенности, безопасности и иммуногенности отечественной гриппозной инактивированной расщепленной вакцины ФЛЮ-М при иммунизации взрослого населения в возрасте 18-60 лет. Установлена низкая реактогенность, высокий профиль безопасности и иммуногенности вакцины ФЛЮ-М. Ключевые слова: вакцина против гриппа ФЛЮ-М, взрослое население 18-60 лет, безопасность, реактогенность, иммуногенность Evaluation of the Reactogenicity, Safety and Immunogenicity of the Domestic Influenza Inactivated Split FLU-M Vaccine in Immunization Adults aged 18-60 Years I. V. Fel'dblyum 1 (irinablum@mail.ru), SAbstract This article presents the results of a simple, blind, randomized, placebo-controlled, single-center, prospective research of the reactogenicity, safety, and immunogenicity of the domestic influenza inactivated split vaccine «Flu-M» in immunization of the adult population of 18-60 years old. Low reactogenicity, high safety profile and immunogenicity of the Flu-M vaccine were determined.
The biotechnology industry is currently one of the most dynamically developing sectors of the pharmaceutical industry, that is why it requires improvement in the personnel management system aimed at increasing the flexibility and adaptability of the organization.The aim of the research is to determine the degree of readiness of the organization’s employees for innovations as illustrated by the example of an export-oriented enterprise.Materials and methods. The source information was collected from the employees of the biotechnological enterprise through a questionnaire survey. The representative sample included 588 respondents. The statistical processing of data was carried out using the specialized software IBM SPSS STATISTICS (IBM, USA, 2017). The consistent readiness of the organization’s employees for innovations was determined using I.O. Zagashev’s methods. To assess the reliability of the psychological test, an internal consistency model with Cronbach’s alpha was applied. Statistical hypotheses were tested by comparing the central tendencies of two independent samples using Student’s t-test and the Mann–Whitney nonparametric test.Results. The distribution results of key motivating factors for personnel showed that motivating factors such as an adequate salary and sustainable employment took the leading positions. However, the assessment of the employees’ consistent readiness for innovations according to I.O. Zagashev’s methods shows a high degree of the personnel’s readiness for changes due to positive emotional perception of any innovations.Conclusion. The results obtained make it possible to arrive at the conclusion that the established team favorably responds to all innovations, and is ready to support them in the future being aware of the organization’s desire for innovations. In the future, the results will be used to determine the required management functions and goals and to develop the personnel management strategy in the context of the knowledge transfer, technology and export policy of the pharmaceutical enterprise.
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