Aim. The aim of the current study was to analyze the genome structure of the M. bovis BCG-1 (Russia) sub-strain, used for the vaccine production, as well as its genome stability within the entire production process. Materials and methods. Whole genome sequencing and M. bovis BCG-1 (Russia) working seed lot and for the last production passage of the sub-strain cultivation from a number of the vaccine batches. Additionally, VNTR sequences of 24 locus analyses, RD patterns comparison, as well as spoligotyping were performed. Results. The whole genome sequence of the M. bovis BCG-1 (Russia) working seed lot was assembled, annotated and deposited to GenBank. On the basis of DU2- and RD-regions analyzes M. bovis BCG-1 (Russia) sub-strain was confirmed to be belonged to BCG Russia strains of DU2-I group. Whole genome sequencing followed by comparative analysis of RD patterns and SNPs confirmed the stability of the vaccine sub-strain genome from the working seed lot to a number of the vaccine batches obtained within the two-years period. VNTR profile and spoligopattern exactly matched the M. bovis BCG-1 (Russia). Conclusion. Thus the M. bovis BCG-1 (Russia) sub-strain genome identity and stability have been studied and demonstrated. The obtained result confirmed the vaccine production process consistency.

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.

Rabies is an acute viral disease caused by a virus of the Rhabdoviridae family of the Lyssavirus genus, which affects the central nervous system and is characterised by absolute mortality. Vaccination is the only way to prevent the disease in humans. One of the products used for vaccination is a cultural concentrated purified inactivated dry rabies vaccine produced by the Federal State Budgetary Institution of Science “Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences” (hereinafter—Chumakov Center).The aim of the study was to examine the structure of the working virus seed of Vnukovo-32 strain used by the Chumakov Center for rabies vaccine production, to assess its genetic stability during production, to explore the possibility of using molecular genetic methods for identification of the production strain in the finished dosage form, and to study the nucleotide sequence of the CVS strain.Materials and methods: Vnukovo-32 rabies virus production strain, working virus seeds, finished batches of the rabies vaccine, CVS fixed rabies virus strain used in the assessment of specific immunity. The molecular genetic study was performed using RT-PCR followed by restriction and sequencing.Results: the paper presents the results of nucleotide sequence analysis of the G gene fragment obtained from the Vnukovo-32 production strain, batches of the working virus seed, and finished batches of the rabies vaccine produced in 2012, 2018, and 2019, and the CVS fixed rabies virus strain used in the assessment of the vaccine’s specific immunity. The study demonstrated that restriction analysis could be used for Vnukovo-32 strain identification at all production stages, including the finished dosage form.Conclusion: Vnukovo-32 and CVS strains used by the Chumakov Center are rabies viruses. Analysis of the nucleotide sequence of the G gene fragment showed that the Vnukovo-32 strain remains stable throughout different production stages. The obtained nucleotide sequence of gene G of the Vnukovo-32 strain was deposited in GenBank (accession number MN116503). The study demonstrated that restriction analysis could be used for Vnukovo-32 strain identification at all production stages, including the finished dosage form.