At present, there are not much data on the clinical use of live recombinant viral vector vaccines. Characteristics of new vaccines should be factored into requirements/recommendations for quality control, preclinical and clinical studies of vaccines in order to enable further risk/benefit assessment. The aim of this study was to analyse current approaches to quality control, preclinical and clinical studies of live recombinant viral vector vaccines. The paper provides an overview of the licensed live viral vector vaccines and those at various stages of clinical trials. The authors analysed Russian, European, American, and Japanese guidelines related to quality issues, preclinical and clinical studies of live viral vector vaccines. The analysis demonstrated that the regulatory requirements for live recombinant viral vector vaccines include assessment of a detailed rationale for vaccine development, including information on the choice of the vector, the origin of the heterologous antigen gene(s), elements related to the transgene(s) expression, as well as assessment of the genetic and phenotypic stability of the recombinant virus, the risk of reversion to virulence or recombination with wild type strains, the potential for virus genome integration into the host cell chromosome, the pre-existing immunity to the vector, the intensity of the immune response elicited by the vector, and the reusability of the vector. The choice and number of applicable toxicological and pharmacological models will depend on these aspects. The results of the analysis of approaches to quality control, preclinical and clinical studies of live recombinant viral vector vaccines may be used in the development of Russian regulatory guidelines harmonised with the international norms and regulations.

The main triggers of new infectious diseases, including those with pandemic potential, are: spontaneous emergence of infectious strains which are more virulent for humans and contribute to transmission of pathogenic microorganisms, environmental changes, social and economic factors, increased contact rates between different regions. A successful pandemic response requires mass immunisation against a specific disease, aimed at the development of herd immunity which is based on the concept of indirect protection of the whole of the population by immunising a part of it. A well-grounded choice of the vaccine platform is central to dealing with this problem. The aim of the study was to compare characteristics of vaccine platforms (attenuated, inactivated, subunit, recombinant vector, DNA, and RNA vaccines) intended for mass immunisation against dangerous and extremely dangerous viral infections with pandemic potential. The study focused on the members of Poxviridae, Orthomyxoviridae and Coronaviridae families as potential pathogens. The vaccine platforms were compared in terms of the following parameters: capability of producing a robust immune response; protective efficacy; time required for vaccine development and testing; ability to produce vaccine in volumes required for mass immunisation; potential obstacles associated with the intended use of the vaccine. It is expected that in the next few decades DNA and RNA vaccine platforms will be most widely used for development of products against dangerous and extremely dangerous viral infections with pandemic potential, regardless of taxonomic groups of pathogens.

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.

At the moment, there are no scientific publications devoted to the technological aspects of production of immunoglobulin solid dosage forms. The aim of the study was to review Russian and foreign literature on production of immunoglobulin solid dosage forms, and present the results of the authors’ own research. The authors analysed data of the National Register of Medicines of the Russian Federation as of mid-2021 on the authorised medicines with a generic name ‘globulin in a solid dosage form’, and summarised their characteristics. They reviewed data on the qualitative and quantitative composition of excipients used in lyophilisation, preparation of tablets and capsules. A number of examples were used to illustrate the effect of technological parameters of immunoglobulin solid form production on the quality of the finished products. It was demonstrated that the production of solid forms of immunoglobulin products prevents aggregation and fragmentation of proteins during storage, which affect the product’s specific activity, and also help to preserve the product’s target characteristics for a longer period of time as compared to liquid dosage forms of immunoglobulins. The results of the study may be used as a basis for development of a manufacturing technology for solid forms of immunoglobulin products.

The Russian Federation puts special emphasis on vaccination-related issues, in accordance with the WHO recommendations. The fact that vaccination, in particular with the diphtheria, tetanus, and pertussis vaccine (DTP vaccine), covers large population groups, accounts for the relevance of research aimed at improving the quality of vaccines. One of the ways to produce vaccines of assured quality is to maintain consistent manufacturing processes that ensure consistency of product characteristics. The stability of the technological processes may be assessed using Shewhart charts. The aim of the study was to assess the production consistency of diphtheria, tetanus, and pertussis components of DTP vaccine using Shewhart control charts. Materials and methods: the study used data from 60 batch summary protocols of a Russian-produced DTP vaccine that were submitted to the Testing Centre of the Scientific Centre for Expert Evaluation of Medicinal Products from September 2017 until April 2020. The study assessed one of the main vaccine quality characteristics—specific (protective) activity of diphtheria, tetanus, and pertussis components. Shewhart charts for the diphtheria and tetanus components were constructed based on the manufacturer’s summary protocols, while Shewhart charts for the pertussis component were constructed based on both summary protocols and the results obtained by the Testing Centre during certification of the product batches. The Shewhart charts were used in accordance with the national standards GOST R 50779.42-99 and GOST R ISO 7870-2-2015. Results: a retrospective analysis of R- and X-charts covering a 2.5-year period revealed some characteristic trends in special-cause criteria. The most alarming situation was observed for the production of the diphtheria component. The technological processes were somewhat safer in the case of the tetanus and pertussis components. The production process lacked due statistical control, which is confirmed by the lack of correlation between the results of the pertussis component activity assessment obtained by the manufacturer and the Testing Centre. Conclusions: during the analysed period, the production of the diphtheria, tetanus, and pertussis components of the DTP vaccine was not always consistent. This highlights the need to conduct research aimed at standardisation of both production processes and control test conditions.

Adeno-associated virus vectors are among the most promising ones for the delivery of transgenes to various organs and tissues. Recombinant adeno-associated virus (rAAV) is able to transduce both dividing and non-dividing cells, has low immunogenicity, and is able to provide long-term expression of transgenes. Modern technologies make it possible to obtain rAAV for in vivo use, but they are not without drawbacks associated with laboriousness, scalability difficulties, and high cost, therefore, improvement of technological schemes for obtaining rAAV is an urgent issue. The aim of the study was to compare different technological approaches to rAAV production based on different conditions of the transfected HEK293 cell line cultivation on a laboratory scale. Materials and methods: HEK293 cell culture, AAV-DJ Packaging System, PlasmidSelect Xtra Starter Kit were used in the study. The technologies were compared using a model rAAV vector with a single-domain antibody transgene fused to the Fc-fragment of IgG1 specific to botulinum toxin. HEK293 cells were transfected with supercoiled plasmid DNA isolated by three-step chromatographic purification. The identity of the rAAV preparation was determined by electrophoresis, immunoblotting, and real-time polymerase chain reaction. Results: the study demonstrated the efficiency of the chromatographic method for obtaining a supercoiled form of plasmid DNA that can be used for efficient transfection of cell culture in order to produce rAAV. The study compared the following processes of rAAV production: using transient transfection and cultivation of the transfected HEK293 cell suspension in Erlenmeyer flasks, adherent culture in T-flasks, and adherent culture in a BioBLU 5p bioreactor on a matrix of Fibra-Cel disks. Conclusions: the data obtained showed the possibility of using the described approaches to purification of plasmid DNA, cell transfection, and cultivation of the transfected cells under various conditions to obtain rAAV samples that expresses the antibody gene. The BioBLU 5p reactor with Fibra-Cel discs was used for the first time to produce preparative quantities of rAAV on a laboratory scale, which increased the adherent surface area during cell culture and transfection, and, as a result, increased the yield of the target product.