One of priority issues of the present-day healthcare system is development of new vaccines and improvement of existing ones due to decreasing immunocompetence of the population, emergence of new infections and reemergence of old ones which were previously thought to be under control. Adjuvants have proven to be integral and important components of modern vaccines, as they enhance immune response to the vaccine antigen. However, despite a lot of effort put into their development, only a small number of adjuvants are currently used in clinical practice.The aim of the study was to systematise literature data on the adjuvants’ mechanisms of action, their specific structure, composition, and stimulation effects that mediate their immunoadjuvant properties. The paper summarises data on adjuvants used as components in licensed vaccines, describes their characteristics, analyses molecular mechanisms of their action in order to establish correlation between their structure and activity, which is important for the development of more efficacious and safe adjuvants. The paper cites advanced developments aimed at enhancing stimulation effects of existing adjuvants. It concludes by stating that the key research area aimed at improving vaccination efficacy is the study of mechanisms that contribute to the development of effective protection against infectious agents, as well as analysis of how to use adjuvants to stimulate the body’s defensive mechanisms, primarily by impacting the innate immunity.

The review is devoted to specific aspects of the development of post-vaccination immunity following immunisation with different types of antiviral vaccines, as well as to ways of increasing immunogenicity of vaccines and effectiveness of preventive vaccination. Vaccines containing highly purified and recombinant antigens obtained using modern technologies have lower reactogenicity and a higher safety profile, but are less immunogenic compared to live vaccines. Effective vaccines have not been developed for many viral infections yet. Therefore, it is critical to search for ways to enhance immunogenic properties of vaccines in order to increase the efficiency of vaccination, and to develop new vaccine formulations that provide reliable protection of the body against infection. The aim of the paper was to analyse specific aspects of immune response development following immunisation with antiviral vaccines, and approaches to increasing their immunogenicity using adjuvants. It reviews different types of antiviral vaccines, as well as specific aspects of immune response development depending on the nature of a specific antigen. The paper substantiates the use of adjuvants to enhance and regulate the induced immune response. It analyses mechanisms that determine the stimulating effect of adjuvants and summarises data on the adjuvants used in the licensed vaccines for human use. The authors highlight the need for further research to increase the efficiency of vaccination and suggest that one of potential solutions is the use of adjuvants based on recombinant human cytokines.

One of the major public health challenges today is development of new vaccines and technologies to optimize the vaccination process. There is a growing scientific interest in vaccine adjuvants that enhance vaccine immunogenicity. At present, numerous studies are underway to develop COVID-19 vaccines, including inactivated and subunit vaccines which contain adjuvants for efficient induction of immune response and solid immunity. The aim of the study was to systematise literature related to the analysis of the structure, mechanisms of action and stimulating properties of vaccine adjuvants (synthetic oligodeoxynucleotides, virosomes, polyoxidonium, sovidone), as well as to summarise data on the effects of adjuvants used in SARS-CoV, MERS-CoV, and SARS-CoV-2 vaccine development studies. The paper analyses the prospects for enhancing the stimulating effect of the adjuvants when used in combination with compounds having a different mechanism of action. It also analyses the results of studies of adjuvanted vaccines against SARS-CoV and MERS-CoV, which may be useful when selecting adjuvants with optimal efficacy and safety profiles to be used in SARS-CoV-2 vaccines under development. It was concluded that understanding of the mechanisms of action of adjuvants that mediate their stimulating effect on the body’s immune system will contribute to safe and effective use of adjuvants to enhance the immunogenicity of both authorised and new vaccines.

Quality control of recombinant interferon (rIFN) products with the help of modern analytical methods, including those used for identification, is becoming increasingly relevant nowadays. Identification is especially challenging in the case of Russian rIFN products that contain not only interferon (IFN) alpha-2b, but also other active ingredients and excipients that hinder the use of physical and chemical methods. Manufacturers of such products use IFN neutralization assay with mono- and/or polyclonal antibodies for identification. The aim of the study was to assess the feasibility of using different types of antibodies in the identification test based on neutralization of IFN antiviral activity in IFN alpha-2b products containing other active ingredients and excipients in addition to IFN. Materials and methods: the following materials were used in the study: MDBK cells, vesicular stomatitis virus, samples of IFN alpha-2b products with different composition and by different manufacturers, mono- and polyclonal antibodies by different manufacturers. Identification of rINFs was carried out by a biological method based on neutralization by specific antibodies of IFN ability to suppress the cytopathic effect of the indicator virus in a cell culture using a reference standard for comparison. Results: both polyclonal and monoclonal antibodies were shown to neutralize the activity of the tested IFN alpha-2b substances. Polyclonal antibodies interact with all products containing the same active ingredients, irrespective of their composition. Monoclonal antibodies interact selectively with some products. Conclusions: polyclonal antibodies can be used for identification of any product containing IFN alpha-2b. The use of monoclonal antibodies for this purpose is limited and depends on the composition of the product.

Резюме. Введение. Известно, что интерферон (IFN), представляющий собой цитокин, является важной частью иммунной системы и необходим для полного выражения иммунного ответа на антигенный стимул. Также считается, что каждый антиген является интерфероногеном. В связи с тем, что интерфероны индуцируют антивирусное состояние посредством связывания со специфическими рецепторами, то эти рецепторы можно определять непосредственно на клеточных мембранах иммунокомпетентных клеток человека. Цель. Оценить интерфероногенность некоторых серотипов вирусов гриппа А по показателям функциональной активности αи γ-интерфероновых рецепторов (IFNAR и IFNGR) на мононуклеарных клетках периферической крови человека (МКПК), индуцированных in vitro вирусами гриппа А различных серотипов. Материалы и методы. Метод основан на выделении лимфоцитов из венозной гепаринизированной крови человека, индуцировании лимфоцитов in vitro при 36,5°С в атмосфере 5% СО 2 , забора образцов в различные временные интервалы, окраске их ФИТЦ-конъюгатом на основе мышиных антиидиотипических антител, структурно имитирующих IFNα и IFNγ человека, то есть антирецепторных антител для IFNα и IFNγ человека, фиксировании окрашенных образцов параформальдегидом и оценке показателей экспрессии интерфероновых рецепторов (IFNR) на проточном цитометре. Результаты. В экспериментах in vitro выявляли интерфероногенность трех серотипов вируса гриппа А/ PR8/34 (H1N1), Краснодар/101/59 (H2N2) и Рязань/6103/87 (H3N2). Мононуклеарные клетки периферической крови (МПК) донора с группой крови «0», резус плюс, индуцировали облученной неинфекционной аллантоисной жидкостью с гемагглютинирующей активностью. Экспрессию IFNAR и IFNGR на МПК выявляли с помощью маркеров IFNR человека, меченых флуоресцеинизотиоцианатом и оценивали в проточном цитофлуориметре. Паралельно сравнивали экспрессию IFNAR и IFNGR на МПК, праймированных и непраймированных малыми дозами IFNα человека. Было установлено, что экспрессия IFNAR на МПК, индуцированных антигеном вируса гриппа А/PR8/34 (H1N1) c высокой гемагглютинирующей активностью была выше у праймированных МПК в сравнении с непраймированными и выше в сравнении с экспрессией IFNAR на МПК, индуцированных антигенами вирусов гриппа А/Краснодар/101/59 (H2N2) и А/Рязань/6103/87 (H3N2) c более низкой гемагглютинирующей активностью. Необходимо отметить, что экспрессия IFNAR на МПК, индуцированных антигеном вируса гриппа А/PR8/34 (Н1N1) и праймированных малыми дозами IFNα, держалась на высоком уровне, начиная с 1 часа с момента индукции антигеном и продолжалась на высоких цифрах в течение 5 часов. Анализ уровня экспрессии IFNGR на МПК, индуцированных антигенами вируса гриппа А различных серотипов показал, что, во-первых, усиление экспрессии IFNGR на МПК, праймированных низкими дозами IFNα не происходило.