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Scientific relevance. In recent years, the development of various vaccines based on novel platforms has underscored the significance of updating regulatory requirements for vaccines. Consequently, clinical trials of viral vaccines need harmonised approaches within national guidelines and the Eurasian Economic Union (EAEU) regulatory framework.Aim. This study aimed to analyse national and international requirements for clinical trials of the efficacy and safety of preventive viral vaccines.Discussion. This article presents an analysis of the guidelines issued by the WHO and leading regulatory authorities on different aspects of clinical trials of viral vaccines. These guidelines place particular emphasis on the immunogenicity of vaccines. The lack of well-established immune correlates of protection for most infections presents a significant problem for assessing the effectiveness of vaccines. Immunobridging studies may be conducted to expand vaccine indications to different populations (such as a new age group). The size of the prelicensure safety database should include data on at least 3,000 vaccinated study participants. For some vaccines, safety studies must assess the risk of disease onset or enhancement due to vaccination.Conclusions. The clinical trial requirements for viral vaccines have been substantially aligned by the WHO and major international regulatory authorities, thereby facilitating the development of harmonised national or EAEU guidelines.

Introduction: Flaviviruses, possessing natural neurotropicity could be used in glioblastoma therapy using attenuated strains or as a delivery system for antitumor agents in an inactivated form., Objective: To investigate the sensitivity of glioblastoma and pancreatic carcinoma cell lines to vaccine strains of yellow fever and tick-borne encephalitis viruses., Materials and Methods: Cell lines: glioblastoma GL-6, T98G, LN-229, pancreatic carcinoma MIA RaCa-2 and human pancreatic ductal carcinoma PANC-1. Viral strains: 17D yellow fever virus (YF), Sofjin tick-borne encephalitis virus (TBEV). Virus concentration were determined by plaque assay and quantitative PCR. Determination of cell sensitivity to viruses by MTT assay., Results: 17D YF was effective only against pancreatic carcinoma tumor cells MIA Paca-2 and had a limited effect against PANC-1. In glioblastoma cell lines (LN229, GL6, T98G), virus had no oncolytic effect and the viral RNA concentration fell in the culture medium. Sofjin TBEV showed CPE 50 against MIA Paca-2 and a very limited cytotoxic effect against PANC-1. However, it had no oncolytic effect against glioblastoma cell lines (LN229, T98G and GL6), although virus reproduction continued in these cultures. For the GL6 glioblastoma cell line, the viral RNA concentration at the level with the infection dose was determined within 13 days, despite medium replacement, while in the case of the LN229 cell line, the virus concentration increased from 1 × 10 9 to 1 × 10 10 copies/ml., Conclusion: Tumor behavior in organism is more complex and is determined by different microenvironmental factors and immune status. In the future, it is advisable to continue studying the antitumor oncolytic and immunomodulatory effects of viral strains 17D YF and Sofjin TBEV using in vivo models.

Introduction: Newcastle disease (ND) is classified as especially dangerous pathogen. Its primary source is an infected or recovered bird. The virus shedding begins just in a day after infection, and virus remains in the body for another 2-4 months after the recovery. The complexity of the final elimination of the causative agent of the disease lies in its ability for long-term preservation in the external environment and the possibility of constant circulation in one complex between groups of birds of different sex and age. Therefore, the main element of protecting birds from ND is immunoprophylaxis that is based on vaccines containing an inactivated ND virus (NDV). The aim of the work ‒ is to optimize the parameters of inactivation of the NDV actual strain H with formaldehyde at final concentrations of 0.01, 0.025, 0.05, and 0.1% under temperature conditions of 20 2 and 37 0.5 C., Materials and Methods: We used a virus-containing suspension of the NDV strain H with an initial biological activity of 10.75 lg EID50/cm3 grown by cultivation in 10-day-old developing chick embryos., Results: On the 16th day after the administration of the tested suspensions of NDV inactivated at different temperatures and concentrations of the inactivant , the geometric mean titers of antibodies to NDV in sera of vaccinated birds were at least 1 : 63 in the hemagglutination inhibition reaction, indicating that the studied inactivated suspensions were antigenically active., Conclusion: The optimal parameters of the inactivation mode (final concentration, temperature and time of inactivation) of the NDV strain H were established. The inactivation process at 37 0.5 C with inactivant concentrations of 0.01, 0.025, 0.05, and 0.1% lasts up to 72, 22, 18, and 12 hours, respectively. The inactivation process at 20 2 C with inactivant concentrations of 0.05 and 0.1% lasts up to 22 and 18 hours, respectively.

This review presents the current state of the problem of development and application of the specific prevention of African swine fever (ASF) with a brief description of its etiology and pathogenesis. The unique nature of the ASF virus (ASFV) determines some limitations and the complexity of solving the problem of vaccine development. Such situation stimulated the development of highly specific diagnostic methods for rapid and accurate detection of the ASFV. In this regard, results of studies, including our own, concerning the comparative analysis of the genome of vaccine and virulent strains of the ASFV, as well as immunodiagnostic approaches to determine causes of high virulence and low protective activity of the ASFV, are briefly presented. Special attention is given to the issue related to the development of safe and effective vaccines against ASF. In this context disadvantages and possible advantages of live attenuated (LAV) and recombinant (RV) vaccines are considered in details. Results of recent studies on the assessment of the immunogenicity of genetically modified vaccines (GMV) which developed in various laboratories around the world are presented. The obtained data indicate that ASF vaccination is currently the most promising measure to stop the spread of this disease in our country and in the world, however, previous experience with ASF vaccination has revealed some problems in its development and application. The significant contribution of foreign researchers to the study of the basics of virulence of this pathogen and the study of its genes functions are noted. The possible further expansion of ASF in Europe and Asia in bordering Russia territories, as well as the established fact of the persistence of ASFV in wild boar population indicate a constant threat of its re-introduction into our country. In conclusion, the importance of developing a safe effective vaccine against ASF and the assessing of the possible risks of creating the artificial sources of the infection in nature as a result of its use is emphasized.

In this paper, we isolate and adapt five strains of rotaviruses for cultivation conditions from children with acute intestinal infections in HEP-2 human cell culture. We characterize the isolated strains according to genotype and ability to increase the infectious titres during five consecutive passages. Crucially, we isolate the rotavirus strain, which has a special ability to adapt to cultivation conditions in human cell culture. This strain is promising for creating effective rotavirus vaccine for Ukrainians, as well as for developing diagnostic test-systems. Finally, we show the inability of the isolated strains to be cultivated in animal cell culture. [ABSTRACT FROM AUTHOR]

Mucosal immunity is realized through a structural and functional system called mucose-associated lymphoid tissue (MALT). MALT is subdivided into parts (clusters) depending on their anatomical location, but they all have a similar structure: mucus layer, epithelial tissue, lamina propria and lymphoid follicles. Plasma cells of MALT produce a unique type of immunoglobulins, IgA, which have the ability to polymerize. In mucosal immunization, the predominant form of IgA is a secretory dimer, sIgA, which is concentrated in large quantities in the mucosa. Mucosal IgA acts as a first line of defense and neutralizes viruses efficiently at the portal of entry, preventing infection of epithelial cells and generalization of infection. To date, several mucosal antiviral vaccines have been licensed, which include attenuated strains of the corresponding viruses: poliomyelitis, influenza, and rotavirus. Despite the tremendous success of these vaccines, in particular, in the eradication of poliomyelitis, significant disadvantages of using attenuated viral strains in their composition are the risk of reactogenicity and the possibility of reversion to a virulent strain during vaccination. Nevertheless, it is mucosal vaccination, which mimics a natural infection, is able to induce a fast and effective immune response and thus help prevent and possibly stop outbreaks of many viral infections. Currently, a number of intranasal vaccines based on a new vector approach are successfully undergoing clinical trials. In these vaccines, the safe viral vectors are used to deliver protectively significant immunogens of pathogenic viruses. The most tested vector for intranasal vaccines is adenovirus, and the most significant immunogen is SARSCoV-2 S protein. Mucosal vector vaccines against human respiratory syncytial virus and human immunodeficiency virus type 1 based on Sendai virus, which is able to replicate asymptomatically in cells of bronchial epithelium, are also being investigated.

The Lassa virus one of the main etiological agent of hemorrhagic fevers in the world: according to WHO estimates, it affects 100,000 to 300,000 people annually, which results in up to 10,000 deaths [1]. Although expansion of Lassa fever caused by this pathogen is mostly limited to the West African countries: Sierra Leone, Liberia, Guinea and Nigeria, imported cases have been historically documented in Europe, the United States of America (USA), Canada, Japan, and Israel [2]. In 2017, WHO included the Lassa virus in the list of priority pathogens in need of accelerated research, development of vaccines, therapeutic agents and diagnostic tools regarding infections they cause [3]. This review describes main technological platforms used for the development of vaccines for the prevention of Lassa fever.

Introduction: Hemorrhagic fever with renal syndrome (HFRS) holds a leading place among natural focal human diseases in Russian Federation. There is no etiotropic therapy for the disease now. The vaccine prophylaxis is the most effective method to control this infection. The main criteria for inactivated vaccines evaluation are its immunogenicity and specific activity.The study purposes were to develop a sensitive and specific real-time PCR method for viral RNA quantification in the inactivated vaccine and to study the correlation between the viral RNA amount and vaccine immunogenicity., Material and Methods: L-segment fragments of the Puumala, Hantaan, and Sochi vaccine strains were selected as diagnostic targets for oligonucleotides and fluorescent probes. The immunogenicity of experimental vaccines was determined by the induction of neutralizing antibodies in BALB/c mice., Results: A highly specific, sensitive and reproducible real-time PCR method has been developed. The analytical sensitivity was 1.24 ± 1.5 x 102 copies/ml for Puumala virus; 1.16 ± 1.4 * 102 copies/ml for Hantaan; 1.32 ± 1.8 * 102 copies/ ml for Sochi, with a virus content of 1.5 ± 0.5 lg FFU/ml; 1.8 ± 0.5 lg FFU/ml and 2.2 ± 0.5 lg FFU/ml, respectively. The viral RNA amount in experimental vaccine preparations inactivated with β-propiolactone was proportional to the neutralizing antibodies titer observed in mice following the immunization., Discussion: It was found that different virus inactivators differently affects the detected viral RNA amount, but not the vaccine immunogenicity, which indicates the same degree of the immunogenic proteins damage. The direct relationship between the viral RNA copy number and vaccine immunogenicity makes it possible to use this criterion for vaccine dosage preparation., Conclusion: The developed method for viral RNA quantification is a promising tool for the specific activity control of the HFRS vaccine.

The paper analyzes the currently available data on the impact of respiratory viruses (RVs) on the exacerbations and clinical phenotype of chronic obstructive pulmonary disease (COPD), as well as on the molecular mechanisms of this impact. It emphasizes the role of acute respiratory viral infections (ARVI), primarily rhinovirus infections (RVI) as the most important triggers of COPD exacerbations and the causes of their severe and long-term course. Particular attention is given to ARVI-induced secondary bacterial infections that worsen COPD exacerbations. The mechanisms of how RVs potentiate chronic inflammation and remodeling of the airway, which are caused by tobacco smoke, are depicted. There are arguments that there is a much greater correlation of the acute episodes showing the more severe respiratory symptoms of COPD with ARVI than can be found by molecular methods for RV verification. The body's genetic and/or acquired excessive response to viral invasion does not reflect the efficacy of antiviral defense and is an endogenous damaging factor in this situation. The role of RVs in the formation of the clinical phenotypes of COPD with frequent exacerbations remains debatable. The need for a search and more active practical introduction of means to prevent virus-induced COPD exacerbations appears obvious. In this regard, the authors identify chemical and mechanical polyvalent bacterial lysates for oral and sublingual administration. In addition to nonspecific stimulation of antiviral defense, these medicines induce antigen-specific mucosal and systemic reactions against bacterial pathogens. The role of ARVI pathogens in COPD exacerbations deserves a greater practical attention focused towards optimizing the treatment of this social disease.

Aim: Study of morphologic and karyologic characteristics of 5 russian human diploid cell lines (HDC)., Materials and Methods: 5 HDC lines and HDC strain MRC-5 were studied; RK-13 and Vero continuous cell lines were used; viruses: rubella (RA27/3), measles (L-16), epidemic parotitis (L-3). Cytogenetic analysis of HDC was performed by using DAPI differential staining method., Results: M-29 line has characteristics that are similar to those of MRC-5 diploid cell strain. M-29 cell culture is not contaminated with foreign viruses, mycoplasmata, does not have oncogenic potency., Conclusion: M-29 line has high virus-productive properties for accumulation of measles, rubella and epidemic parotitis vaccine viruses and may be recommended as a substrate for the production of antiviral vaccines.

The overview presents the currently available data on porcine epidemic diarrhea (PED) and its etiological agent, a coronarovirus of swine. Economic losses from the disease are very serious. The overview discusses whether serially Vero cell propagated PED virus strains may be used as live vaccines.

The authors consider the present tick-borne encephalitis situation in our country and prospects for this infection control.

The modern view of the role of enteroviruses in the eradication of poliomyelitis is presented. Enteroviruses were discovered in the XX century. In the 1950s they caused great epidemics of poliomyelitis and serous meningitis in many countries of the world. The introduction of oral poliomyelitis vaccine (OPV) into medical practice made it possible to eliminate the epidemics of poliomyelitis in a short time. Poliomyelitis morbidity was reduced to sporadic cases and in a number of regions disappeared. OPV produced non-specific influence also on the epidemics of serous meningitis, as well as on a case incidence. The eradication of poliomyelitis viruses and the cessation of immunization with OPV will not result in eradication of paralytic diseases. Paralytogenic viruses of 20 serotypes circulate in nature, and some of these viruses are capable of causing the outbreaks of severe paralytic diseases. The authors propose either to retain immunization with OVP as tour immunizations with monovaccine of type 2, or to create new live enterovirus vaccines on the basis of avirulent enterovirus strains.

The last quarter of the 20th century in the Russian Federation was marked by an unprecedented increase in the incidence of tick-borne encephalitis (TBE) with its peaks in 1996 and 1999 when as high as 10,000 cases of the disease were notified. Its highest incidence was recorded in the Regions of the Urals and Siberia. As many as 70-80% of the persons who felt ill were urban dwellers who had been infected mainly in the anthropurgic foci occurring in abundance in the environs of cities and towns. It was found that the area of TBE had been expanded and virus-infected ticks had actively penetrated into the urban parks and small public gardens. There were as many as 70 TBE-endemic regions. As of now, it has been ascertained that TBE foci are generally combined with other infections transmitted by Ixodes ticks and caused by viruses, bacteria, rickettsia and protozoa. This result is the occurrence of mixed infections, which requires new approaches to their diagnosis, treatment, and prevention. The prevention of TBE is conventionally based on vaccination of high-risk groups comprising mainly "forest" occupations. Under the present conditions, the strategy of TBE control should be radically revised towards mass vaccination of the population living in the highly endemic areas, which will drastically reduced morbidity in the country.

The paper presents data on the design and practical medical use of vaccines for the prevention of urgent viral infections, including those against poliomyelitis (oral poliomyelitis vaccine), tick-borne encephalitis, hepatitis A, rabies, and enteroviris 71. It shows the basic lines in the improvement of manufacture and biological control of vaccines and in the development of a new vaccine for prevention of hemorrhagic fever with the renal syndrome.

Long-term experiments have provided conditions for the optimal conditions for reproduction of vaccine strains of poliomyelitis, measles, tick-borne and Japan encephalitis on the continuous cell lines. This makes it possible to solve one of the most urgent problems of modern biotechnology, namely to refuse to use primary cell cultures in vaccinology and to apply a more accessible, safe, and reference biological substrate that are stable cell lines.

The hepatitis B core antigen (HBcAg) was used to present the HIV epitopes and mimics selected by phage display. The HIV epitopes were inserted into the el loop of HBcAg. The influence of insertions on the ability of chimeric HBcAg to assemble itself was studied. Special soft was made use of to detect the regularities between certain physical-and-chemical properties of amine-acid residua (belonging to an inserted alien peptide) and the presence or loss of the ability of HBcAg to assemble itself. Recommendations are provided of how to overcome difficulties related with the presentation of alien epitopes.

Several cell cultures were compared and examined for their capability to support reproduction of Classical Swine Fever Virus (CSFV). Experimental conditions of virus cultivation were optimized. The subculture of primary lamb testicular (LT) cells was selected for large cell cultivation of CSFV. In contrast to many cell lines, these cells were free of Bovine Viral Diarrhea Virus (BVDV) contamination partly due to liquid nitrogen storage and gamma-ray sterilization of serum used in the growth media. The vaccine strain CS of CSFV was obtained in the titers of 6.7-7.7 TCID50/ml under the optimal conditions of virus reproduction in the LT cells.

In 1988 the World Health Assembly resolved to eradicate poliomyelitis globally by the year 2000. The work continues. The problem arose how to quit the system of mass immunization with oral poliovirus vaccine (OPV) without trouble and to achieve the disappearance of polioviruses worldwide. After the cessation of the OPV use a certain number of vaccine viruses may remain that will circulate among the ever growing number of nonimmune population. Live enterovirus vaccines prepared from nonpathogenic serotypes of ECHO virus are proposed for application to stop the circulation of vaccine poliovirus. These vaccines will make it possible to eliminate the remaining vaccine viruses from circulation and to complete the process of worldwide poliomyelitis eradication.

Experimental batches of dried dust-like vaccine on the basis of Newcastle disease virus, strain La Sota, have been prepared. The technology of the preparation of the vaccine includes the lyophilization of the technical fluid of the culture under study, milling dried biomass and mixing the pulverized biomass with excipient. As revealed in the process of this work, lyophilization ensures high concentration of the virus in dried biomass and its pulverization, a high content of the target fraction of biomass particles in the vaccine preparation with the moderate inactivation of the bioagent. By mixing the pulverized biomass with excipient the required concentration of the viable virus in the finished product may be achieved. The viability of the bioagent during the storage of the dried vaccine under conditions, determined by optimum storage temperature and time, has been found satisfactory.

Time course of specific humoral immunity is studied in 186 Macaca mulatta spontaneously infected with hepatitis A virus (HAV). Immunity parameters are characterized quantitatively and qualitatively and their similarity to those in human hepatitis A (HA) is demonstrated. Repeated HA was reproduced in 12 seropositive Macaca mulatta infected with HAV-MR in high doses. The disease was characterized either by periodical virus release with feces for 1.5-2 months (10(4) ID50) or by that together with a notable increase of SGPT for 1.5-4 months (10(5) ID50) without morphologic changes in the liver, indicating a lesser severity of infection. Reinfection was associated with a rapid expressed increase of class G anti-HAV titers to 20,000-74,000 and no class M antibodies. Virus release with feces in the absence of the main specific diagnostic criterion, IgM antibodies, may be epidemiologically significant. Hyperimmune sera from monkeys with reinfection are intended to be used as the antibody component of immune diagnostic agent.

An increased level of the procoagulant activity (PCA) has been observed in porcine leukocytes in vitro infected with virulent or vaccine strains of hog cholera virus in comparison with intact cells. PCA was similarly induced in infected leukocytes from swine immune to hog cholera virus. Increased PCA levels were detected in culture medium with leukocytes from intact and immune animals infected in vitro with both virulent and vaccine strains of hog cholera virus in comparison with the PCA levels in culture medium with intact cells.

Clinical and immunological studies were carried out in 697 patients (913 eyes) for a more accurate diagnosis of herpetic involvement of the posterior segment of the eye by the focal allergic test (FAT) based on the delayed type hypersensitivity phenomenon. FAT consists in detection of the focal reaction in the eye, regularly developing after 2-3 intracutaneous injections of herpetic vaccine to types I and II herpes simplex virus in a dose of 0.2 ml every other day. The reaction is assessed by clinical and functional methods: visometry, campimetry, biomicroscopy, 9-point test, Amsler network, Hedinger's phenomenon, photocolor stress test, Rabkin's polychromatic tables, fluorescent angiography of the fundus oculi, electrophysiological methods, critical frequency of flash fusion, reflection microscopy of the corneal endothelium, and color campimetry realized on an IBM-compatible computer before and after vaccination of patients with suspected herpetic involvement of the eye. FAT was positive in 395 (56.6%) patients in 568 (62.2%) eyes. Examination of the threshold relative brightness sensitivity before and after FAT revealed positive results in 70% of patients. FAT is an accurate non-invasive method for the diagnosis of various manifestations of intraocular herpes. Relative safety of FAT recommends it for clinical practice to be used in the diagnosis of herpetic involvement of the posterior segment of the eye.

Four strains isolated from patients with hemorrhagic fever with the renal syndrome and from field mice, natural hosts of Hantavirus, were examined in order to choose a functionally active strain fit for the development of inactivated Hantavirus brain vaccine. Virulent strain PM-10508/89 isolated from mouse lungs was chosen. The strain was highly virulent for newborn mice and rats: 100% of infected mice aged up to 24 h and 75% of rats developed an acute lethal infection upon challenge. The incubation period of Hantavirus adapted to mouse brain was decreased from 19 to 7 days. The infective titer of the virus in brain suspension was 0.1 to 6.5 lg LD50/ml. The strain was highly immunogenic and possessed a high hemagglutinating activity.

The level of specific antibodies in the blood of Cercopithecus aethiops monkeys with experimental Marburg hemorrhagic fever appreciably affects the incidence of lethal outcomes in immunized animals infected with Marburg virus. This effect manifests starting from the titers as low as just 1:100. The level of humoral immunity with the specific antibody titer of at least 1:100 depends on the method of antigen preparation. Humoral response was higher upon challenge with formalin-inactivated virus isolated from the blood plasma of infected guinea pigs.

The protective properties of experimental vaccine against tick-borne encephalitis (TBE) were studied. The vaccine was prepared by conjugating colloid gold with soluble TBE antigen. The protective properties of experimental and commercial vaccines were compared by the mean survival time and protection coefficients after one and three vaccinations of mice infected in doses of 100,000 and 10,000 LD50. In animals immunized with experimental vaccine the protection coefficient and mean survival time were, respectively, 1.3-1.5 times and 10-30% higher than in mice immunized with commercial vaccine. Assessment of the therapeutic activity of antibodies induced by the experimental and commercial vaccines after 1 and 3 immunizations showed the mean survival time to be 1.2-1.7 times longer in animals injected antibodies from mice immunized with the experimental vaccine.

Comparative analysis of the characteristics of tick-borne encephalitis (TBE) strain 205 used for the production of vaccine against TBE and of its variants obtained by passages in mouse brain showed the stability of such properties as infective activity, neurovirulence, sensitivity to physical (heating to 50 C) and chemical (sodium deoxycholate treatment) factors. At the same time increased neurovirulence of variants 205/M10 and 205/M20, which undergone through 10 and 20 passages in white mouse brain, for low-sensitive Syrian hamsters was revealed. Use of a panel of 5 monoclonal antibodies to protein E and of 4 monoclonal antibodies to protein E and of 4 monoclonal antibodies to protein NS3 helped differentiate between not only strains 205 and Sofyin, but between variants of strain 205 as well.

Tick-borne encephalitis virus strain 205 was characterized by such sign as the presence of negative colonies. In the swine fibroblast cell line the population of the strain was represented mainly by large plaque (67.3%). Medium-sized plaques prevailed in chick embryo fibroblast cell culture. Protamine sulfate and magnesium chloride reduced the period of incubation, increased the resolving capacity of the plaque method and the proportion of medium- and small-sized plaques. Agarose B rendered the virus colonies less contrasting. The production strain and the clones of its population were found to have pronounced reproductive and protective properties. The S+ variants of the virus exhibited the highest reproductiveness.

The prospects of using the methods of gene engineering for the development of viral vaccines are considered. The technological and biological barriers hampering the introduction of these biotechnological methods into the practice of vaccinal prophylaxis are analyzed. The work points out that in the near future successes may be achieved in synthetizing the internal proteins M and NP of influenza viruses and similar proteins of paramyxoviruses and rhabdoviruses, as well as in using yeast for the production of vaccine against hepatitis B.

Injection of living vaccinia virus to the mesenteric vein of rabbits leads to its accumulation in liver in high concentration. In the other series of experiments vaccinia virus inactivated with gamma-radiation was inoculated into the mesenteric vein. Later on the animals were sacrificed at various dates. Homogenates were prepared from their liver. Comparative study of these homogenates made it possible to reveal increased immunogenic activity of homogenate obtained 24 hours after intravenous inoculation of inactivated vaccinia virus into animals. Immunogenic activity of this homogenate was more clearly manifested than immunogenic activity of the antigen itself--inactivated vaccinia vorus. Neither original inactivated vaccinia virus nor inactivated virus absorbed by Kupffer cells induced antibody formation. It is supposed that vaccines may be prepared from various viruses or tumor cells treated with macrophages with subsequent chemical extraction of the most immunogenic fraction.

Various natural and synthetic interferon inducers stimulate postvaccination immunity to tick-borne encephalitis virus in mice. This capacity was found not only in macromolecular synthetic polyribonucleotides such as (poly I)-(poly C), (poly G)-(poly C), (poly A)-(poly U) and substances with much lower molecular weight such as copolymers of vinylpyrrolidone with maleic anhydride, crotonic acid or metacrylic acid but also in a low molecular interferon inducer tiloron. These and other interferon inducers examined (endotoxin S-typhi, statolon) exhibited no parallelism between the intensity of their stimulating effect of immunogenesis and levels of interferon production induced in mice and the associated resistance to tick-borne encephalitis. The results indicate a possibliity of using various interferon inducers for stimulation of post-vaccination immunity to tick-borne encephalitis.

Proceeding from the known data various theoretical and experimental approaches to the construction of gene-engineering vaccines are considered. Gene-engineering subunit vaccines of the first generation are based on isolation of the genes coding for the synthesis of full length capsid proteins with the main antigenic determinants and their subsequent expression in suitable recipient cells. Initial idea of the microbiological synthesis as the main way for production of any antiviral vaccines was not confirmed by the later development. Now for this type of vaccines eucaryotic systems are widely employed using the animal virus vectors and the animal cell cultures. Gene-engineering subunit vaccine of the second generation appears to be a chimeric protein with built-in antigenic determinants of different viruses and maximal immunogenicity in monomeric form. The last point reopens the perspective to use a microbiological synthesis for the production of antiviral vaccines. Besides that the chemically synthesized polypeptide antiviral vaccine will be used widely. In gene-engineering subunit vaccines of the third generation it is possible to use not the natural antigenic determinants which often are characterized by high level of the primary structure changes but artificial (non-natural) antigens, that are the capsid protein conservative regions which under natural conditions of infection or immunization do not induce the protective antiviral antibodies. The recombinant DNA technology in addition to subunit type vaccine allows to construct living vaccines which represent a DNA-containing attenuated virus with build-in natural or synthetic gene of the capsid or chimeric protein with antigenic determinants of another viral species.

The influence of some members of the togavirus family (tick-borne encephalitis, dengue 2, Langat, Tahyna) and the vaccines used extensively for prophylaxis of tick-borne encephalitis and yellow fever on the immune response to a heterologous antigen was studied. The tick-borne encephalitis, Langat and dengue 2 viruses as well as the tick-borne encephalitis and yellow fever vaccines were found to alter the immune response of the recipient to subsequent administration of sheep erythrocytes. Some togaviruses (tick-borne encephalitis, Langat, yellow fever, dengue 2) stimulate formation of specific hemolysin-synthesizing cells, while others (Tahyna, dengue 2) under certain conditions may inhibit heterologous immune response. The nature of the influence depends upon genetically determined factors in the recipient, however, the conditions favouring the adjuvant or immunodepressive effect of one virus are not identical to those for another.