Studies of Immunobiological Properties in <i>Francisella tularensis</i> Vaccine Strain 15 NIIEG under Extended Storage Conditions

Investigated have been 8 cultures of Francisella tularensis strain 15 NIIEG (lyophilized in 1953, 1966, 1969, 1987, 1990, 2003, 2012, and 2013, respectively) stored at the State Collection of Microorganisms of the Scientific Center on Expertise of Medical Application Products. It is established that the majority of cultures has maintained their immunobiological properties. However, it is of note that liophilization does not prevent F. tularensis strain 15 NIIEG from changes in its residual virulence under extended storage. Revealed is the fact that LD50 for 7 cultures of tularemia microbe strain is within the limits of 100-250 microbial cells (m.c.). At the same time, residual virulence for the strain which dates back 1966 is 7.3·105 m.c. Immunogenic activity rates in F. tularensis 15 NIIEG strain cultures range within specified limits. Apart from this, F. tularensis 1987 strain does not comply with the established requirements to the “specific safety”, as subcutaneous inoculation with 5·109 m.c./ml caused death of Guinea pigs within the scheduled observation time. Demonstrated is the necessity in maintaining constant stability of the original immunobiological properties in Francisella tularensis strain 15 NIIEG under extended storage conditions

Review of global use of licensed vaccines and development of new vaccines for the prevention of pneumococcal infection

Streptococcus pneumoniae infection is the most common cause of high morbidity and mortality among children under 5 years of age, immunocompromised people, and the elderly. Despite significant success, the approved pneumococcal conjugate and polysaccharide vaccines are of limited efficacy, providing protection against a small fraction of the known pneumococcal serotypes. The rapid spread of multidrug-resistant strains exacerbates the global challenge of treating infection caused by S. pneumoniae. At the same time, the emerging new strains dictate the need to include new serotypes into vaccines. In view of this, further improvement of vaccines for the prevention of pneumococcal infections is an urgent task. The aim of this study was to review advances in the development of polysaccharide, conjugate, whole-cell pneumococcal vaccines, as well as vaccines based on protein antigens and vaccines with an antigen delivery system. Genomics and proteomics data have helped to improve approaches to the creation of polysaccharide and protein-based vaccines, as well as whole-cell vaccines with the potential for population prophylactic coverage against various pneumococcal serotypes that are not included in the licensed pneumococcal vaccines. The method of antigen delivery to the cell is of great importance in the development of vaccines. The most promising strategy for improving pneumococcal vaccines is the creation of vaccines based on bacterium-like or synthetic particles carrying several antigens, including pneumococcal surface proteins. In conclusion, it should be noted that top-priority vaccines are those that provide a wide range of protection against circulating pneumococcal serotypes and, in addition to eliciting a systemic immune response, also induce local immunity

Improvement of Approaches to the Verification of the Vaccine Strain <i>Francisella tularensis</i> 15 NIIEG during Long-Term Storage

The aim of the study was to improve the methods for verifying the vaccine strain Francisella tularensis 15 NIIEG during long-term storage under current conditions.Materials and methods. The paper summarizes the results of studying the phenotypic and genetic properties of lyophilized cultures of the vaccine strain F. tularensis 15 NIIEG (1953, 1966, 1969, 1987, 1990, 2003, 2012 and 2013) stored at SCEMAP for a period of one to 60 years.Results and discussion. Previous studies have revealed that freeze-dried cultures of F. tularensis 15 NIIEG generally had the characteristics of the vaccine strain, with the exception of deviations from the regulatory requirements for residual virulence and specific safety. The stability of preservation of deletions in the pilA and pilE genes (the region of differentiation RD19) and the genes encoding lpp lipoprotein (RD18) in the vaccine strain, which was stored for various periods of time in a lyophilized state, has been confirmed. The vaccine-strain-specific mutation C178404T (by the genome of F. tularensis LVS strain, GenBank NCBI no. CP009694) has been identified, and an approach to determine it has been developed. The data obtained are promising as regards using the above deletions in the RD18/RD19 regions in combination with the C178404T mutation to assess the authenticity of the vaccine strain using molecular genetic methods. Thus, the conducted retrospective analysis of the data on the cultures of tularemia microbe vaccine strain from the 1940s to 2013 and the gathered experimental data, made it possible to supplement the uniform requirements for the manufacture, study, maintenance, storage and movement of F. tularensis 15 NIIEG vaccine strain with new evidence. Based on the results obtained, the authors have drawn a draft methodological recommendations of the federal level “Vaccinal strain Francisella tularensis 15 NIIEG: order of handling”

Assessment of Residual Virulence of Francisella tularensis 15 NIIEG Vaccine Strain Based on Long-term Observations

Objective of the study is to assess and analyze the long-term data on annual control of residual virulence of Francisella tularensis 15 NIIEG vaccine strain for clarifying the value of the parameter and amending the regulatory documentation. Materials and methods. Utilized were 8 vials containing lyophilized cultures of vaccine strain F. tularensis 15 NIIEG dated 1953, 1966, 1969, 1987, 1990, 2003, 2012, and 2013, manufactured at different industrial sites. To gather additional information on residual virulence of F. tularensis 15 NIIEG strain, evaluation of quality control files of 76 lyophilized cultures in vials was performed, out of which 48 strains manufactured at the premises of Odessa Bacterial Products Enterprise in 1980, 1987, and 1990, and 28 – at Joint Stock Company Scientific Production Association on Medical Immunobiological Preparations “Microgen”, Omsk Bacterial Products Enterprise, in 2003–2013. Results and discussion. Assessment of the parameter has revealed that out of 8 tested cultures of F. tularensis 15 NIIEG strain of various date of lyophilization 7 cultures have virulence rate ranging within 1·102 – 2.5·102 mc, LD50 of the strain dated 1966 is 7.3·105 mc (the standard range 1·102 – 2·106 mc). Obtained in the course of analysis of quality control files on F. tularensis 15 NIIEG strain, stored in lyophilized form at (19±1) °C, data demonstrate that residual virulence stays within the specified limits. Amendments regarding the value of “Residual virulence” parameter have been introduced into the regulatory documentation, the level ranging within 1·102 – 5·103 mc

Forecasting of Brucellosis Morbidity Rates in the Russian Federation Using Wald Method

Objective of the study is to conduct epidemiological analysis of official statistical data on brucellosis morbidity rates over the period of 2005–2014 in different constituent entities of the Russian Federation, using Wald method. Materials and methods. Utilized were recording and reporting documents of the Federal Service for Surveillance in the Sphere of Consumers Rights Protection and Human Welfare, FBHI “Federal Center of Hygiene and Epidemiology” of the Rospotrebnadzor, and WHO information resources.Results and conclusions. Studies of peculiarities of epidemic process development over the long-term period have allowed for identification of entities that are the most affected by the diseases. The results obtained on the morbidity rates in the Russian Federation over the period of 2005–2014 testify to the fact that first comes North Caucasian Federal District (NCFD) (62 %), next go Siberian (SbFD) (16 %) and Southern (SFD) (13 %) Federal Districts, second and third lines of the list respectively. Other regions account for 9 % of the load. The largest share of morbidity in NCFD entities belongs to the Republic of Dagestan – 62 %. Thereat, annual increment rate is 5.54 cases, which points to stabilization and some downward trend. Application of this morbidity rate prediction tool provides for in-time planning of clinical-diagnostic, prophylactic, and anti-epidemic measures in brucellosis foci. Wald method for forecasting of morbidity can be used for other infectious diseases too

Эффективность и безопасность вакцин для профилактики холеры

Cholera is an acute diarrheal disease caused by toxigenic strains of Vibrio cholerae O1 and O139 serogroups. It still remains a major  global healthcare problem. According to WHO, about 100,000 people die from cholera every year, despite the modern methods of  treatment, improvement in the quality of drinking water, sanitation and hygiene. In recent years, oral cholera vaccines have proved an  effective tool for preventing and curbing cholera epidemics.  According to the WHO Ending Cholera — A Global Roadmap, mass  vaccination should help reduce the mortality resulting from cholera  by 90 % worldwide by 2030 and eliminate the disease in 20  countries. The review outlines the main historical stages in the  development of cholera vaccines: parenteral, chemical, inactivated and live oral vaccines. The paper compares active  ingredients and excipients used in Dukoral®, mORC-VAX®, Shanchol®, Euvichol®, Vaxchora®, Oravacs® and the cholera bivalent chemical vaccine. The results of international multicenter clinical trials of oral inactivated, live and  chemical cholera vaccines are analysed. Issues related to efficacy and safety studies of cholera vaccines are considered.Холера — острое диарейное заболевание, вызываемое токсигенными штаммами Vibrio cholerae О1 и О139 серогрупп, по-прежнему остается одной из основных проблем мирового  здравоохранения. Несмотря на существующие методы лечения и улучшение качества  питьевой воды, санитарии и гигиены, ежегодно от холеры, по оценкам ВОЗ, умирают около  100000 человек. В последние годы одним из эффективных способов предупреждения и  ликвидации эпидемий холеры является применение оральных холерных вакцин. Согласно  Глобальной дорожной карте ВОЗ, массовая вакцинация должна помочь к 2030 г. добиться  снижения смертности от холеры на 90 % в мире и элиминирования заболевания в 20  странах. В обзоре изложены основные исторические этапы создания холерных вакцин:  парентеральных, химических, инактивированных и живых оральных вакцин. Представлено  сравнительное описание состава действующих и вспомогательных веществ вакцин  Dukoral®, mORC-VAX®, Shanchol®, Euvichol®, Vaxchora®, Oravacs® и вакцины холерной  бивалентной химической. Проанализированы результаты международных многоцентровых клинических исследований оральных инактивированных, живой и химической холерных  вакцин. Рассмотрены вопросы, касающиеся изучения эффективности и безопасности вакцин, используемых для профилактики холеры