Current State of the Vaccine Prophylaxis of Particularly Dangerous Infections

Considered are the problems of handling of the vaccine strains Yersinia pestis EV NIIEG, Bacillus anthracis STI-1, Francisella tularensis 15 NIIEG, and Brucella abortus 19 BA, utilized for manufacturing of live vaccines against particularly dangerous infections, in connection with absence of normative legal document, specifying the algorithm for storage and handling of strains after production stage throughout the shelf-life (10 years). It is indicated that under current conditions the system of handling and record keeping on the transfer of strains of vaccines against particularly dangerous infections is compromised. It has led to disruption of interdepartmental cooperation in the transfer, testing, maintenance, and storage of the latest manufactured batches

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

Botulinum toxin preparations: areas for improvement and issues of standardisation

Scientific relevance. Botulinum toxin preparations are a good example of using a deadly toxin as a unique therapeutic agent. However, there are many unresolved issues related to biotechnology, biological activity, interchangeability, and standardisation of botulinum toxin preparations. Aim. To review current opportunities for improving therapeutic botulinum toxin preparations.Discussion. This review covers botulinum toxin type A preparations and unresolved issues related to them. In the absence of international non-proprietary names recommended by the World Health Organisation or by the Board of the Eurasian Economic Commission, domestic and imported botulinum toxin type A preparations approved in Russia have only similarity-based grouping names. In addition, manufacturers name botulinum toxin preparations at their discretion. Therefore, classifying these preparations under a common nomenclature is essential for clear identification, adequate selection, and correct prescription. Several studies have shown significant variability across botulinum toxin type A preparations. Due to the identified differences in qualitative and quantitative characteristics, botulinum toxin type A preparations cannot be considered similar, which raises the issue of their interchangeability and bioequivalence. To resolve this issue, a unified classification and naming system for botulinum toxin preparations should be established and documented in regulatory standards. According to the literature, manufacturers of botulinum toxin preparations use in-house reference standards. Hence, the same activity unit resulting from toxicity and efficacy studies may express a different protein load for each botulinum toxin preparation. Keeping that in mind, the authors discuss the development of a single international potency standard for existing and pipeline botulinum toxin type A preparations. Conclusions. The article describes novel pharmaceutical compositions containing botulinum toxin, including those in late development. Summarised data from clinical studies on the safety, efficacy, and cost-effectiveness of botulinum toxin type A preparations can guide prescribing decisions

Concerning the Application of Heterologous Preparations in Practical Healthcare

The paper presents the data on the assessment of the demand for heterologous drugs and highlights the need for their use in practical healthcare. Currently, 15 heterologous immunoglobulins and sera are registered in the Russian Federation. Nine of them are against bacterial and viral infections (anthrax, diphtheria, tetanus, botulism, rabies, anti-gangrenous), one – against snake venom, five other – anti-thymocyte immunoglobulins produced by domestic and foreign manufacturers. Analysis of the data has demonstrated that anti-rabies immunoglobulin, anti-diphtheria and anti-botulinic sera, A, B and E type are the most in-demand. Production of other therapeutic drugs from this group, for instance, anti-gangrenous serum, tends to decline. Adequate provision of medical curative and preventive institutions with these preparations is a significant element in timely treatment of infectious diseases such as anthrax, diphtheria, tetanus, botulism, rabies, as well as snake bites. In prophylaxis and treatment of certain diseases (emergency aid in case of anthrax, rabies, venomous snake bites) heterologous preparations still oftentimes do not have an alternative. The key problem in regulation of heterologous preparation circulation is absence of quality, efficacy and safety criteria applicable to other immunobiological preparations. Development of unified requirements to standardization of heterologous sera and immunoglobulins of various specificity, principles of efficacy and safety evaluation is necessary for harmonization of current guidelines on medical use. Earlier elaborated by WHO approaches to heterologous sera to venoms of snakes can be used for monitoring and harmonization of normative legal documents on the improvement, evaluation of quality, efficacy and safety of alternative drugs being in circulation in the pharmaceutical market of the Russian Federation

Characteristics of Phenotypic and Genetic Properties of <i>Francisella tularensis</i> 15 NIIEG Vaccine Strain with an Extended Storage Period

Investigated have been cultural-morphological, biochemical and genetic properties of lyophilized cultures of F. tularensis 15 NIIEG vaccine strain, accumulated within 60-years term and deposited at the State Collection of Pathogenic Microorganisms of Scientific Center on Expertise of Medical Application Products. The studies undertaken have demonstrated that storing of the strains in such a form at low temperatures, does not prevent changes of their genetic and phenotypic properties to the full extent. It is established that F. tularensis 15 NIIEG strain lyophilized in 1953, 1966, 1969, 2003 and 2012 maintains its immunogenic properties when cultivated on nutrient media Ft-agar with or without addition of blood, based on dissociation rates (87-99 %) of SR-colonies. While F. tularensis 15 NIIEG strain 1990 contains specified amounts (not less than 80 %) of immunogenic colonies if cultivated on nutrient media with the addition of blood, and fails to meet the requirements - if cultivated without. Identified in F. tularensis 15 NIIEG strain 1987 SR-colony decrement of 70-75 % in case of cultivation with or without addition of blood testifies to the deterioration of its immunogenic properties. RAPD and ERIC typing has showed high stability of the genome of F. tularensis 15 NIIEG cultures lyophilized at different times. Tularemia microbe vaccine strain has unique RAPD and ERIC profiles, insignificant alteration of which is observed upon storage of pathogen subculture in the dried from

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

Development and Main Stages of Introduction of the Preparation “Cholera O139 Diagnostic Fluorescent Immunoglobulins”

– for environmental objects. Application of the preparation for practical purposes was considered to be promising, and it was recommended for State registration as a product of medical application

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