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Introduction: Specific prevention of a number of infectious diseases has been introduced into the vaccination schedule. The production of immunoprophylactic drugs, in order to establish standard properties, including safety and specific effectiveness, requires strict adherence to manufacturing regulations, and the reliability of the results obtained requires monitoring of these parameters. The specific effectiveness of vaccine preparations is standardized according to the indicators of stimulation of specific antibody response formed in the body of vaccinated model biological objects., Objective: Determination of the immune reactivity of white mice to vaccination with the QazVac vaccine to establish the possibility of using them as a biological model in assessing the immunogenicity of the vaccine instead of Syrian hamsters., Materials and Methods: The immune reactivity of model animals was assessed by the seroconversion rate, dynamics of antibody titers to the SARS-CoV-2 virus formed in the body after vaccination with the test vaccine. In the case of seropositivity of animals before administration of vaccine or placebo, the level of immune reactivity was calculated by the difference in antibody titers between control and vaccinated animals or by the difference in antibody titers before and after immunization. Specific antibodies were detected and their titer was determined using a neutralization reaction., Results: The research results showed that the tested biological models had approximately the same immune reactivity to the administration of the QazVac vaccine, confirmed by the level and dynamics of antibody titers. When analyzing the fold increase in antibody titers in comparison to those of control animals, Syrian hamsters were more reactive compared to mice. But SPF white mice were standardized in their lack of the immune reactivity to SARS-CoV-2 virus before the immunization., Conclusion: The data obtained indicate that the immune reactivity of white mice to the administration of the QazVac vaccine in terms of the rate and dynamics of the formation of virus-neutralizing antibodies is approximately equivalent to the immune reactivity of Syrian hamsters. Before immunization with the vaccine, SPF white mice, in contrast to Syrian hamsters, do not have humoral immunity specific to the SARS-CoV-2 virus. The immune reactivity equivalent to that observed of Syrian hamsters and the absence of antibodies to the SARS-CoV-2 virus at a baseline indicate the superiority of the use of white mice in assessing the immunogenicity of vaccines against COVID-19 and/or obtaining specific factors of humoral immunity.

Aim: Direct comparative studies of immunogenicity and protective effect of live cold-adapted (ca) and inactivated vaccines against type A influenza., Materials and Methods: Groups of mice were immunized intramuscularly (i/m) or intranasally (i/n) twice with inactivated or live ca vaccines based on wild-type parent strain A/Krasnodar/101/59 (H2N2) and the corresponding ca donor strain A/Krasnodar/101/59/30CE/5MDCK/l/7/4 (H2N2), respectively. Immunogenicity was determined by HAI antibodies in sera and lungs (extracts) against both vaccine strains. Protective effect--by the level of wild-type strain in lungs of immunized mice after the infection., Results: Live ca and inactivated vaccines based on similar strains increase immunogenicity and protective effect when administered via different routes in varying patterns. A significant increase of immunogenicity was only observed for i/m (sera antibodies) and i/n (lung antibodies) administration of the live ca vaccine, and could be determined by antigenic features of the vaccine strains. At the same time, all the vaccine variants and administration routes induced at least partial protection from infection compared with unimmunized control. However, complete protection from infection was only noted for the i/m administered live ca vaccine., Conclusion: A combination of immunization variant and vaccine type determines immunogenicity and protective effect, and their interconnection requires further studies using all the possible combinations of preparations and administration routes as well as determination of induction of various components of the immune system.

Comparative evaluation of live attenuated and inactivated influenza vaccines based on data from direct comparative studies is necessary for ensuring the most effective and safe vaccination against influenza. Analysis of direct comparative preclinical and clinical studies of inactivated and live cold-adapted (ca) influenza vaccines showed that published data are inconsistent and limited for some population groups. Live ca vaccines may be promising as an alternative or addition to inactivated vaccines especially for mass vaccination against influenza in children as well as in the elderly when combined with inactivated vaccines. Further studies of inactivated and live ca influenza vaccines in direct comparative studies that control the administration route and vaccine strain production as well as development and confirmation of objective criteria of live attenuated influenza vaccine effectiveness evaluation are necessary.

A reliable protective activity of the home-manufactured immunomodulators (ridostin, polyribonate glucosemuramyl-dipeptide, Mylife, and peptidoglycane-160) was detected in mice. The mice were infected with the equine eastern encephalomyelitis virus (EEEV, an alphavirus), or with the tick-borne encephalitis virus (TBEV), or the yellow fever (YF) virus (both flaviviruses). The effect of the urgent vaccination reliably increases when the vaccination is combined with the immunomodulators listed above. Under the alphavirus infection, the combined effects of the vaccine and ridostin were accompanied with increased specific humoral and cellular immune response (virus-specific antibodies and adoptive transfer of immune lymphocytes). The combined application of the specific vaccine and ridostin can be recommended for clinical trials of TBE in the foci of Infection.

Aim: Confirmation of immunostimulating effect of an original low molecular weight germanium organic compound (LMW-GOC) during immunization of mice with Vaxigrip vaccine., Materials and Methods: The experiments were carried out in CBA mice divided into 4 groups: control, those that received Vaxigrip influenza vaccine intraperitoneally, those that received LMW-GOC intraperitoneally and those that received both preparations at once. Effect of the preparations administered was evaluated by flow cytofluorometry based on changes of CD3, CD4, CD5, CD8, CD19, CD25, Foxp3, NK1.1, gammadelta T, MHC II, TLR2, TLR4, TLR9 expressing cell content in mice spleens. The content of the colored cells was determined at normal, 24 hours and 7 days after the administration of the preparations. Statistical treatment of the data was carried out by using Win MD 128 program package., Results: LMW-GOC can enhance the effect of Vaxigrip vaccine that is expressed by an increase of content in spleen of some lymphocyte subpopulations 24 hours and 7 days after the intraperitoneal administration. In some cases LMW-GOC increases the content of some lymphocyte subpopulations in mice spleen after administration as a monopreparation, i.e. without the vaccine. LMW-GOC suppressed stimulating effect of the vaccine on the spleen content of various lymphocyte subpopulations in none of the observations., Conclusion: By using cytofluorometry method it is possible to form an understanding of an elevated role of various types of cells in the development of immune response to the vaccine as well as regarding additional enhancement of this response during administration of LMW-GOC to mice. The effect of the preparation is manifested for a few days after its administration. The preparation manifests adjuvant properties and after further studies may be suggested for use as an adjuvant.

Influenza reassortant viruses A/SPb/HK/09(H1N1), A/Astana/HK/2009 (H5N1), A/Otar/HK/2010(H3N8), and A/Perth/ HK/2011(H3N2), carrying surface antigens of different subtypes, were constructed on the basis of new potential unified donor strain A/HK/1/68/162/35(H3N2). The virulence and reproduction activity of the obtained reassortants were tested. The safety of the candidate live and inactivated influenza vaccines produced from the reassortant viruses was demonstrated. The study demonstrates that A/HK/1/68/162/35 can be used as a unified donor for attenuated and high-yield vaccine reassortants.

Aim: Study of immunogenicity and protective efficacy of a novel inactivated vaccine with chitosan against influenza A/H1N1/2009., Materials and Methods: Influenza virus A/California/7/2009 (H1N1) strain was used in the study. Mice were immunized twice (21 day interval) with experimental samples of inactivated influenza vaccine: No. 1--without the addition of chitosan, No. 2--with addition of chitosan. The blood was obtained 21 days after the first and 10 days after the second immunization with the vaccines and was treated with RDE. Antibody levels were evaluated in HI reaction., Results: HI reaction method showed that antibody titers induced after immunization of vaccine No. 2 were higher than those induced after immunization with vaccine No. 1. Evaluation of protective efficacy of the vaccines against an experimental form of influenza infection in mice showed that after immunization with vaccine that does not contain chitosan the level of virus accumulation does not differ from the control statistically significantly (p < or = 0.05), at the same time the level of virus accumulation in the lungs of infected animals immunized with chitosan containing vaccine significantly (significantly with 95% probability) decreased by an average 3.01g when compared with control., Conclusion: Comparative analysis of immunogenicity and protective efficacy of experimental samples of inactivated influenza vaccine against influenza A/H 1N1/2009 showed that the vaccine with the addition of chitosan stimulates the formation of a higher immune response and promotes a more significant suppression of influenza A infectious agent reproduction in the lung target-organ.

Aim: Study dynamics of IFNalpha, IFNgamma, TNFalpha cytokines in healthy adults after administration of inactivated subunit monovalent influenza vaccine, A/California/7/2009 (H1N1) strain., Materials and Methods: Levels of IFNalpha, IFNgamma, TNFalpha cytokines were studied in blood sera of 58 mostly healthy adults aged 18 - 60 years. Kits for enzyme immunoassay determination of cytokine levels (Vector-Best, Novosibirsk) were used in the study. Antibody titers to A/California/7/2009 (H1N1) strain were determined at analogous time by using microneutralization reaction (MNR)., Results: Changes in the level of IFNalpha, IFNgamma, TNFalpha in healthy volunteers immunized by pandemic influenza vaccine were evaluated. Vaccine was safe. Two immunizations did not result in an increase of TNFalpha level that is an additional evidence of vaccine safety. IFNalpha level had a tendency to increase in vaccinated volunteers. IFNgamma levels in volunteers with normal level of this cytokine (below 10 pg/ml) were increased significantly after the second immunization (from 2.66 +/- 2.48 to 5.21 +/- 2.56). Correlation analysis showed that there is a strong negative association between IFNalpha, IFNgamma and seroconversion.

Aim: To assess effect of continued immunization of mice from CBA line with inactivated group A streptococcal vaccine on levels of serum cytokines and number of stromal bone marrow progenitor cells in immunized mice and in heterotopic transplants after different variants of transplantation., Materials and Methods: CBA mice were immunized during 3 weeks with heat-killed vaccine prepared from group A streptococci type 5. Levels of pro- and antiinflammatory cytokines were measured with BioPlex device. Number of stromal progenitor cells was determined on quantity of colonies formed by cells explanted to monolayer cultures., Results: Significant 2.3-fold increase of number of stromal progenitor cells in femoral bone marrow of immune mice was demonstrated. Experiments with heterotopic transplants showed that bone marrow in transplants of mice immunized with streptococci--variant Normal-->Immune (N-->1)-- is defective both on efficacy of cloning and number of stromal progenitor cells. Even short-term presence of stromal tissue in immune organism (variant I -->N) significantly changed these parameters, especially at late time after transplantation. In serum of immune mice changes of cytokines levels, especially TNFalpha, were observed. The level of the latter was decreased (mean--2.5-fold) in all immune serum samples compared to normal serum., Conclusion: Immunization of mice with group A streptococci leads to changes in stromal tissue and, possibly, to damage of microenvironment functions including hemo- and lymphopoiesis.

Aim: To perform preclinical study of subunit monovalent adsorbed inactivated influenza vaccine "PANDEFLU" [strains A/California/7/2009 (HIN1)v]., Materials and Methods: Preclinical study of acute toxicity on experimental animals (assessment of vaccine's toxic effects on organs and body systems; pathomorphologic study of organs and tissues after administration of the vaccine; assessment of its influence on hematologic indicators)., Results: It was shown that administration of the vaccine did not lead to death of animals as well as to decrease of body mass or development of pathologic, focal sclerotic changes in parenchymal cells and visceral stroma; the vaccine did not negatively change hematologic and biochemical indicators of blood. Results of necropsy and histological study after acute administration of the vaccine in standard dose did not lead to irritation, inflammation or destruction of tissues in the place of inoculation. The vaccine was apyrogenic and did not have local irritating and allergenic effects. Status of animals after acute inoculation of the vaccine demonstrated its good tolerability and safety in doses exceeding standard human doses more than tenfold. CONCLUSION. Performed research demonstrated absence of contraindications for conduction of clinical trials of "PANDEFLU" vaccine on limited contingent of volunteers.

Prevention of recurrent genital herpes with the inactivated herpetic divaccine Vitaherpavac against herpes simplex virus types 1 and 2 has a number of advantages over the most commonly used symptomatic therapy: it ceases or significantly reduces the number of recurrences and accordingly prolongs a relapse-free interval, abolishes viremia and the manifestations of clinical symptoms of recurrences, induces no dependence to the vaccine. Coadministration of the Vitaherpavac vaccine and the immunomodulator Giaferon has been shown to have some advantage over vaccination only. The new formulation of the agent as suppositories (per rectum) not only enhances the immunogenicity and protective properties of the vaccine, but also reduces the frequency of its application and makes more convenient for patients to use.

Phase I clinical trial of inactivated virosomal split influenza vaccine "Grifor" was conducted in the Mechnikov Research Institute of Vaccines and Sera as accredited base for such trials. Forty healthy volunteers (males and females) aged 18 - 50 years consented to participate in the trial. Reactogenicity, safety, and immunogenicity of new Russian influenza vaccine were assessed. Analysis of obtained results showed that there was evidence of safety and low reactogenicity of the vaccine as well as of its high immunogenic characteristics, which satisfied both the EMEA's Committee for Proprietal Medicinal Products criteria and requirements of Federal Service for Surveillance for Protection of Consumers Rights and Human Welfare (MU 3.3.2.1758-03) for inactivated influenza vaccines.

In the overwhelming majority of countries inactivated vaccines, which form mainly humoral immunity, are used for prevention of influenza. The objective of the study was to assess the combined effect of inactivated influenza vaccine and chitozan on cellular immunity in CBA line mice. Intramuscular administration of 2 doses (with 4 week interval) of inactivated influenza vaccine and chitozan resulted in increased cytotoxic activity of splenic NK cells against NK-sensitive cell line K562 as well as in increased proliferative activity of mononuclear leukocytes, and numbers of CD3 T-lymphocytes, NKT cells, B-lymphocytes in animals' spleens. Combination of inactivated influenza vaccine with chitozan modulated the number MHC II-expressing cells by eliminating the increased reactivity of immune system cells as well as increased the number of MHC I-expressing cells. This point on the activation of cellular properties, which recognize intracellular pathogens, and thus on activation of both humoral and cellular factors of immune response. It can be proposed that inclusion of chitozan in the vaccine allows to modulate switching of the immune response from Th-2 to Th-1 type.

Addition of 0.5% chitosan derivative to parenteral inactivated influenza vaccines increased antibody titers in the single immunization of mice by 4-5 times while double immunization showed 6-to-10-fold increases as compared with immunization without chitosan. Moreover, chitosan-containing vaccines induced the generation of antibodies to the drift variants of influenza virus. When the mice were given inactivated influenza virus A/H5N2 vaccine containing chitosan, immunogenicity and protective efficacy were much higher than when they received a vaccine containing no chitosan.

Biological characteristics of C. trachomatis author's strain MT-2A (serovar D) is presented. Stages of development on its basis the experimental formalin-inactivated vaccine against Chlamydia were described. Humoral and cellular immune response to the vaccine administered on 3-dose immunization schedule in conjunction with polyoxidonium as adjuvant was studied. Significant immunological efficacy of the vaccine was shown. T- and B-cell immune responses were characterized. Titer of IgG antibodies against Chlamydia in blood serum after 3rd dose of the vaccine was 10,880+/-1,817.76. Assessment of T-cell response showed that reaction of delayed hypersensitivity with formation of granuloma presented in 60% of animals. Proportion of immunoblasts in reaction of blast-transformation was 29.3+/-2.8%. Perspectives of further studies of the developed corpuscular vaccine against Chlamydia are discussed.

The quality of drugs used in the Russian Federation to prevent and diagnose tick-borne encephalitis (TBE) was analyzed. The TBE vaccines made in Russian were shown to be as effective as those manufactured in foreign countries and to have the similar production techniques and quality indices therefore they may be interchangeable in the population's vaccination. The specific activity of has recently increased in terms of the content of TBE virus antibodies. In Russia, a wide range of enzyme immunoassay systems have been designed and manufactured for the detection of human serum (plasma) IgM and IgG antibodies to TVE virus and for that of TBE viral antigen in the biological objects, primarily in the ticks.

Assessment of clinical course of asthma and IgG response in children with asthma immunized with pneumococcal polysaccharide vaccine (Pneumo 23) and influenza vaccine (Vaxigrip). 78 children aged 4 - 17 years old were allocated to two groups. Children from the 1st group were immunized against pneumococcal infection and influenza; children from 2nd group were immunized against pneumococcal infection only. Rate of asthma exacerbations in the 1st group of children decreased by 1.7 times compared with the period before vaccination, whereas the same rate in the 2nd group of children decreased by 1.5 times. It was accompanied by the increase of IgG level to antigens of pneumococcalvaccine in blood, which was observed in both groups. Vaccination did not result in increase of IgE levels. Immunization of children with asthma against pneumococcal infection with polysaccharide vaccine or combined immunization against pneumococcal infection and influenza reduced rate of asthma exacerbations and led to formation of immunity to vaccine strains of Streptococcus pneumoniae. Vaccination did not lead to sensitization of children.

The paper deals with an investigation of an immune response in BALB/c mice immunized with tick-borne encephalitis (TBE) vaccine and infected with TBE virus and in non-immunized mice. The parameters of specific humoral (IgG and IgM) and cellular (gamma-interferon (IFN) and cell proliferation) immunities and the activity of cytokines (necrosis tumor factor-alpha, interleukin (IL)-1beta, IL-2, IL-6, IL-10, and IL-12) were studied. There were significant differences in the specific and nonspecific immune response of immunized and non-immunized animals. Noteworthy is the difference in the time course of changes in the levels of IL-6, IL-2, IL-12, and gamma-IFN in the immunized and non-immunized animals.

The results of the comparative analysis of the immunological effectiveness of the anti-influenza vaccine Vaxigrip, the inferferon inductor Arbidol and their combination in 125 elderly persons are presented. In the process of investigations the immunomodulating activity of the preparations under study was noted; this activity was manifested by the increase of the absolute and relative number of cells, carrying markers CD3+, CD4+ and CD16+, but not CD8+, CD19+ and CD25+, the normalization of the immunoregulatory index and the stimulation of the phagocytic function in the absence of essential influence on the level of HLA-DR+ expression and the concentration of immunoglobulins of the main classes. An increase in the frequency of seroconversions and the multiplicity of growth in the titers of specific antibodies to influenza viruses A (H1N1 and H3N2) and B, most pronounced in persons immunized with the vaccine simulianeouslywith the injection of Arbidol, was established.

Influenza remains a serious health problem, annually causing epidemics embracing up to 10% of the population of the world, and at the periods of pandemics this number may rise 4- to 6-fold. In the overwhelming majority of the countries the prophylaxis of influenza is carried out at present out with the use of inactivated vaccines. One of such vaccines is the highly purified split vaccine Vaxigrip (Aventis-Pasteur, France), permitted for use in Russia since 1992. The article contains the review of the data of literature, as well as the materials provided by the authors, which indicate that the preparation has low reactogenicity (also for children starting from the age of 6 months) and high reactogenic properties, leading to antibody formation at protective levels with respect to all three components of the vaccine. The vaccine has been found to ensure pronounced prophylactic efficacy for 70-90% of vaccinees and a decrease in influenza morbidity even in case of using the preparation a week before the onset of the epidemic. This shows the advantage of Vaxigrip in comparison with other inactivated vaccines.

Data obtained in the recent years on developing the viral inactivated mucosal vaccines by applying the mucosal-adhesive adjuvants are presented in the survey. Progress achieved in designing the mucosal influenza vaccines and mucosal vaccines against a variety of other viral infections is pointed out. Cross-protection against variations of a virus within its subtype limits as well as overcoming of a negative influence of parent antibodies produced on the immunogenicity of live-vaccines', which were used at young age, were observed in the intranasal administration of viral mucosal vaccines. A number of shortcomings of bacterial toxins used as mucosal-adhesive adjuvants as well as problems, which may arise when the viral mucosal vaccines are used on a large-scale basis due to a need in their two- and-threefold intranasal administration, are in the focus of attention.

The humoral response of mice and rabbits to the injection of whole-cell pertussis vaccine (PV) and acellular pertussis vaccine (APV), developed at the Mechnikov Research Institute for Vaccines and Sera (Russian Acad. Med. Sci.) in Moscow, was studied. In the sera of immunized animals antibodies to the antigenic complex were determined in the direct hemagglutination (DHA) test, specific antibodies to filamentous hemagglutinin (FHA) and pertussis toxin (PT)--in the enzyme immunoassay (EIA) and antibodies neutralizing PT in a cytopathogenic dose (CPD)--in neutralization test on Chinese hamster ovary (CHO) cells. In mice and rabbits immunized with APV the antibody titers determined in the DHA test were higher than those in the animals immunized with PV. Specific antibodies titers to FHA and PT in the sera of rabbits immunized with APV were also higher than those in the sera of rabbits immunized with PV. High dilutions of sera taken from the animals immunized with APC neutralized 4-16 doses of PT in the neutralization test on CHO cells. The most important result of this study was the detection of a more pronounced immune response in the animals immunized with APV in comparison with that induced by PV according to the results obtained in EIA and in the test of PT CPD neutralization on CHO cells.

Methods for evaluating the potency of inactivated rabies vaccines are reviewed. Shortcomings of the traditional NIH method and advantages of modern rapid immunological in vitro methods (antibody binding test, radial immunodiffusion test, enzyme linked immunoadsorbent assay) for estimation of antigenic activity of vaccines are discussed.

Antigenic structure of Ebola virus (EV) (strain Mayinga) nucleocapsid protein VP35 was analyzed using monoclonal antibodies to EV VP35 and polyclonal antibodies to EV. EV protein VP35 was shown to have antigenic sites inducing the production of antibodies in animals. For better characterization of protein VP35 antigenic structure. EV gene encoding the full-length VP35 was cloned in vector pQE31 as a recombinant fusion protein (rec.VP35). The antigenic and immunogenic properties of rec.VP35 and EV VP35 were compared by ELISA and Western blot analysis with polyclonal and monoclonal antibodies. Antibodies of positive sera and VP35 MAbs cross reacted with the analyzed antigens. The topography of epitopes on EV VP35 and rec.VP35 was studied using MAbs and polyclonal antibodies to rec.VP35 in a competitive antibody binding assay. Two epitopes of one site were identified on these proteins. These epitopes are present on infectious virion protein VP35 and are stable during physicochemical exposures.

This paper sums up the results of controlled field clinical trials of adult and childhood variants of Harvix, inactivated vaccine from hepatitis A. The vaccine is weakly reactogenic and safe. After a single injection of Harvix-1440 vaccine to adults the percentage of seroconversions in previously seronegative individuals was 80.6%, with the mean geometrical antibody titer 119 mIU/ml. In children aged 3-10 years the percentage of seroconversions after a single injection of Harvix-720 vaccine was 100%, the mean geometrical of antibody titer being 427 mIU/ml. Results of laboratory control and field clinical trials recommend both variants of Harvix vaccine for prevention of hepatitis A in the Russian Federation.

A comparative study was carried out to assess reactogenicity and immunogenicity of inactivated influenza vaccines (Begrivac, Vaxigrip, Grippol, Influvac, and Fluarix), licensed in Russia. Immunization of the elderly demonstrated low reactogenicity and high immunogenicity for all vaccines. Concomitant chronic diseases had no influence on the vaccine immunogenicity levels, which testifies to the benefit of vaccination in this age group. In the group of vaccinated the highest seroconversion to all vaccine strains was found for Vaxigrip (82-89% for group A viruses and 86% for group B virus); the vaccine demonstrated the highest level of diagnostic increase of antibody titers to all 3 viruses, i.e. 69.0% (p < .05), with 22.0% of vaccinees gained antibodies to 2 vaccine viruses (91.0% in total). The number of positive responses to 3 and 2 strains in subjects immunized with Fluarix, Begrivac and Influvac reached 85.0%, 85.0% and 83.0% respectively. It is noteworthy that the combination of surface antigens of A and B flu viruses in low concentration with polyoxidonium immune modulator in Grippol induced intensive immune response.

BALB/c mice were immunized with recombinant plasmid DNA pSVK3-ENS1 and pcDNAI-NS3 containing, respectively, genes E-NS1 and NS3 of tick-borne encephalitis (TBE) virus. Antibodies to TBE virus proteins were detected in the blood sera of the immunized animals by the method of the enzyme immunoassay. Though the titers of virus-specific antibodies in the sera of mice immunized with protein vaccines exceeded those registered after immunization with DNA vaccines, essential protective immunity was observed after the use of both vaccines.

Specific antibody immune response to vaccination with commercial inactivated trivalent vaccine A(H1N1) + A(H3N2) + B (IgA, IgG, IgG, subclasses G1, G3, G4, and accumulation of antiCD8) was studied in subjects aged 20-95 years. The initial immune status before vaccination is significant for a positive immune response to the vaccine. Subjects responding to immunization by an increment in specific IgG had a much lower prevaccination level of these antibodies than subjects without these Ig conversion. Antibody immune response to vaccination depended on patient's age. All vaccinees aged 20-25 years developed an increment in IgG to at least one of influenza antigens used. Specific postvaccinal immune response to inactivated influenza vaccine included accumulation of G1, G3, and A antibodies, but not G4 or E antibodies. This latter fact suggests the absence of sensitizing effect of vaccination. In elderly subjects an increment in G1, G3, and A antibodies may not involve an increase in the total level of IgG. In part of elderly subjects secretion of specific antibodies was observed in the presence of increased concentration of antilymphocytic antibodies (antiCD8), indicating a possibility of autoimmune reactions in subjects of this age after injection of inactivated influenza vaccine.

Cellular (lymphocyte proliferation activity--LPA), humoral (serum antibodies), and secretory (IgA antibodies from the upper respiratory tract) immune responses were compared in 45 subjects aged 66-95 years, vaccinated with two influenza trivalent A(H1N1) + A(H3N2) + B vaccines: Russian live attenuated cold-adapted reassortant (LIV) and USA inactivated split-virus (IIV) vaccines. None of immunization protocols suppressed LPA after in vitro stimulation of cell culture with homologous virus antigens and nonspecific polyclonal mitogen (PHA). Simultaneous LIV + IIV vaccination was the most effective method of immunization, inducing humoral, secretory, and cellular immunity. LIV more actively than IIV stimulated the lymphoproliferative immune responses. Fluctuations in the mean values of cellular, humoral, and secretory immunity were in good correlation over the entire period of observation (19 weeks). Analysis of individual immune responses showed that a significant increase in quantitative parameters of LPA was observed only in 39-52% vaccinees.

The word deals with the results obtained in the study of the reactogenicity and immunological activity of concentrated and inactivated tissue-culture tick-borne encephalitis vaccine, manufactured by the Chumakov Institute of Poliomyelitis and Viral Encephalitides, in the immunization of children and adolescents. The vaccine proved to be moderately reactogenic and exhibited pronounced immunological activity. In 91.5% of the immunized children the fourfold increase of the antibody level was observed. On the basis of the data obtained in this study the tick-borne encephalitis vaccine was recommended for use in medical practice for the prophylaxis of tick-borne encephalitis among children and adolescents.

In the controlled field trial the reactogenicity, safety and antigenic activity of a new concentrated inactivated leptospirosis vaccine after its administration in one and two injections of 0.5 ml were studied in comparison with those of the existing commercial vaccine, introduced in two injections in doses of 2.0 and 2.5 ml. The new experimental vaccine exhibited low reactogenicity and was found to be safe and highly immunogenic when introduced in a single injection of 0.5 ml. As shown in this trial, the immunogenic characteristics of immunization made in a single injection were not inferior than those obtained as the result of immunization made in two injections, yielding high percentage of seroconversions (89.8% to 98.3%) with respect to 4 Leptospira serogroups and leading to the production of the protective titers of corresponding antibodies. The existing commercial vaccine was inferior to the experimental one in antigenic activity (the frequency of seroconversions, antibody titers). The results of the trial make it possible to recommend the experimental concentrated leptospirosis vaccine for use in medical practice in a dose of 0.5 ml introduced in a single injection.

The results of the study of the effectiveness of using vaccine Vaxigrip for the prophylaxis of influenza in organized groups of adults are presented. The vaccine was found to have high epidemiological effectiveness (the epidemiological index was 2.6), moderate reactogenicity and pronounced immunological activity (the protection level was 89.0-100.0%). The vaccine may be recommended for the prophylaxis of influenza among adults.

Russian cultural concentrated inactivated vaccine protecting from hepatitis A--Hep-A-in-vac was used for immunization of children. The vaccine is slightly reactogenic and completely safe in children aged 3-17 years vaccinated twice in a dose of 0.25 ml. Double immunization of seronegative children with a 1-month interval led to conversion in 89.7% children. In 64.1% children titers of antibodies to hepatitis A virus reached 20 mIU/ml and higher, which indicates rather high antigenic activity of the vaccine.

To improve the vaccinal prophylaxis of influenza, the comparative study of live trivalent influenza allantoic vaccine, dried, for adults, produced by the Irkutsk Enterprise for Immunological Preparations (Russia), and inactivated trivalent influenza split vaccine, obtained from Wyeth-Ayerst Company (USA), as well as schedules of their combined use for the vaccination of elderly persons, was carried out. The examination of 600 subjects revealed that the vaccines were well tolerated; the combined use of these two vaccines, as well as the use of the inactivated influenza vaccine (IIV) alone, ensured high immunogenic activity (60.0-80.0% of seroconversions). The live influenza vaccine (LIV) stimulated the production of specific antibodies only in 19.0-35.0% of the vaccinees; most of these vaccinees exhibited positive reaction only to one of the vaccine strains. Following the injection of LIV, the level of postvaccinal immunity was retained for at least 6 months. In the vaccinees receiving both vaccines the tendency towards a decrease in mean geometric titer values was less pronounced (0.2-0.4 log2) than in those receiving only IIV (0.5-0.7 log2). At the period of the rise of influenza morbidity, the contamination rate in the vaccinees with the positive postvaccinal dynamics of antibodies was low (26.0%). The indices of effectiveness were 3.8 for combined vaccination, 3.5 for IIV and 2.6 for LIV. The schedule of vaccination with IIV with the possible revaccination LIV 3-4 weeks later was recommended.

A total of 159 subjects aged 65-87 years were immunized with live cold-adapted reassortant influenza vaccine (CRIV), inactivated influenza vaccine (IIV), and with both vaccines (CRIV + IIV) one year, two and three years running. The frequency and intensity of accumulation of postvaccinal secretory and humoral antibodies in elderly subjects depend on the scheme of immunization and history of vaccinations. Combination of the two vaccines effectively stimulated both components of immunity and ensured a longer persistence of postvaccinal antibodies in high concentrations. Immunization with CRIV + IIV for three years resulted in a gradual increase of the intensity of prevaccination secretory and humoral immunity. Before the third seasonal immunization the majority (63-75%) of vaccinees had antibodies in protective titers.

The results of the study of the reactogenicity, safety and immunological activity of Russian cultural vaccine against hepatitis A are presented. The vaccine was found to have specific safety, moderate reactogenicity and pronounced immunological activity. In addition, the study of the prophylactic efficiency of the vaccine in the pre-epidemic period of the outbreak of hepatitis A morbidity in a group exceeding 14,000 adults was carried out. The study revealed high prophylactic efficiency of the vaccine (its efficiency rate was equal to 97.7%). On the basis of materials thus obtained vaccine "Hep-A-in-Vac" was recommended for use in medical practice for the prophylaxis of hepatitis A among adults.

The comparative study of the immunogenic and protective properties of V. cholerae, grown in vivo and in vitro, and cell walls and lysates obtained from these organisms. In the mouse protection test the efficacy of preparations obtained from vibrios grown in vivo did not exceed that of the preparations obtained from V. cholerae agar cultures.

The parameters of nonspecific immunity (interferon, interleukin-1, tumor necrosis factor, and natural killers) changed in immune BALB/c mice after challenge with Machupo virus in doses of 1000 and 5000 PFU. After challenge with 1000 PFU the activity of the above parameters increased during the first three days and no cases of animal death occurred. After challenge with 5000 PFU the maximal values of interferon, interleukin-1, tumor necrosis factor, and natural killers were observed on days 5-7, the animals dying at the height of these values. Hence, the formation of specific humoral and cell-mediated immune response in BALB/c mice immunized with inactivated Machupo virus does not protect the animals from infection with the homologous virus in a dose of 5000 PFU. High mediator activity of nonspecific immunity factors on days 5-7 after infection augments the disease course and leads to earlier death of vaccinated animals in comparison with the same dose of the virus in nonimmune mice.

During three seasons at the period of 1992-1996 immunization of elderly persons, living in homes for old people, against influenza with inactivated influenza vaccine (IIV) was carried out. Altogether 856 persons were immunized intranasally, 581 persons constituting the control group. For comparison, 4,825 healthy young adults aged 18-24 years were immunized under similar conditions. The study revealed that the intranasal immunization of elderly persons with IIV, made in two administrations, was safe and stimulated sufficient humoral and secretory immunity: the level of seroconversions was 24.3-41.0% to type A(H1N1) influenza virus, 29.6-50.7% to type A(H3N2) influenza virus, 39.3-59.6% to type B influenza virus; the level of diagnostic IgA conversions was 31-38%. Immunization produced a pronounced prophylactic effect (the effectiveness index 1.6-1.7), as well as decreased the total mortality level by half. The tactics of the immunization of persons from high risk groups against influenza in medical practice is discussed.

Inactivated culture vaccine against tick-borne encephalitis (TBE) FSME-Immun-Inject produced in Austria ("Immuno") was compared to vaccine produced in the Institute of Poliomyelitis and viral encephalitis by immunological activity, safety, reactogenicity. In mice, no significant differences in protective activity of the vaccines were found when test-strains were diverse strains of TBE virus. Seroconversion in the sera from the vaccinated two times was not significantly different by the level of antibodies determined for both eastern and western serotypes of TBE virus.

As a result of the high-dose gamma-irradiation (50 kGy) of corpuscular pertussis vaccine (CPV), pertussis radiovaccine (PRV) was obtained. Compared with CPV, PRV was shown to possess reduced toxicity and higher protective potency. Its adjuvant properties remained at the initial level, while its leukocytosis-promoting and histamine-sensitizing activities drastically decreased. Moreover, PRV produced less pronounced stimulating effect on the proliferation of hematopoietic stem cells, but, in contrast to CPV, was shown to capable of protecting mice from lethal radiation.

Regularities in the formation of autoantibodies to human IgA, IgM, IgG and their fragments, such as F(ab')2, Fab, Fc, in donors immunized with influenza vaccine (44 subjects) and staphylococcal toxoid (15 subjects) were studied with regard to the dynamics of specific immune response. After immunization with staphylococcal toxoid autoimmune reactions were registered only in the precipitation tests during 3-5 weeks of observation. In donors immunized with influenza vaccine the induction of isotypically heterogeneous autoimmune reactions was established. These reactions were represented mainly by IgA and IgG autoantibodies to immunoglobulins of different classes and their fragments. The duration of autoimmune reactions registered in this group of donors was specially noteworthy. The levels of autoantibodies to most of the antigens under study remained significantly elevated for 6 months. After immunization with influenza vaccine the presence of direct correlation between the level of specific immune response and the level of autoantibody formation was established.

Comparative analysis of the specific activities of various batches of Hep-A-in-Vac vaccine showed that the immunologic efficacy of the agent directly depended on the content of hepatitis A virus antigen in the vaccine dose. The results of studying the immunogenicity of the agent on volunteers are compatible with the results of experimental studies and indicate that the test of guinea pigs adequately assesses this characteristic. Assessment of the immunogenic properties of Hep-A-in-Vac prepared using improved technology indicates that Russian vaccine injected three times in a dose containing at least 40 U EIA ensures 87.5% seroconversion in adult seronegative volunteers with the mean geometrical titer of antibodies to hepatitis A virus equal to 683 mIU/ml.

Data on the immunopathogenesis of Ebola fever in laboratory animals are presented and the efficacy of some methods of vaccine prophylaxis discussed. Antiviral immunity induced in guinea pigs by injection of inactivated viral agents did not protect them from infection, whereas injections of a nonlethal strain of the virus in ascending doses led to the formation of immunity preventing the development of disease upon inoculation with a lethal strain in high doses. The role of some viral peptides in the development of immune response is shown and variants of recombinant constructions for the prevention of Ebola fever are offered.

The influence of the vaccination of mice and volunteers on the activity of natural killer cells (NKC) and K cells, the effectors of natural and antibody-dependent cytotoxicity of cells, was studied. Both types of killer cells were found to take an active part in the vaccinal process during the whole term of observation. The changes revealed in this study were characterized by two phases. At the first contact with the antigen a rise in the activity of killer cells was observed; this rise was then followed by their pronounced suppression, reflecting total structural changes which occurred in the infected macroorganism. Repeated injections of the antigen induced mainly the activation of K cells. The use of protective antibodies contained in the commercial preparation of antianthrax globulin exerted influence on the duration of changes in the activity of NKC and K cells of the infected animals.