Monitoring the effectiveness of influenza vaccines annually enables the development of measures aimed at decreasing influenza incidence, hospitalization, and mortality rates. The epidemiological effectiveness of several Russian domestic influenza vaccines was evaluated in St. Petersburg in the 2018-2021 epidemic seasons. Male and female participants (N = 6912) aged 18-23 were monitored from 2018 to 2021. Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri inactivated influenza vaccines were used for immunization. In 2018-2019, when the vaccine strains fully matched the circulating influenza viruses, prophylactic vaccination resulted in a 2.7 to 7.1-fold reduction in influenza cases. The protective effectiveness of the vaccines against influenza and acute respiratory infections (ARIs) totalled 52.4%, reaching 73.0% effectiveness against influenza after laboratory confirmation. In the epidemic season 2019-2020, when the circulating viruses and vaccine strains did not fully match, the incidence of influenza and ARIs reduced twice due to vaccination; the total vaccine effectiveness against influenza and ARIs amounted to 50.0%. The Grippol Plus, Ultrix, and Ultrix Quadri vaccines proved to be the most effective, demonstrating a total effectiveness of 70.6%-75.0% and a 65.5%-83.5% effectiveness against influenza A and B. In the 2020-2021 epidemic season, no data on the preventive effectiveness of the influenza vaccines could be obtained due to the outbreak of COVID-19 and the absence of detectable influenza virus shedding in the study participants. The results obtained are consistent with WHO experts’ estimates which indicate that modern influenza vaccines reduce the incidence of influenza in adults by 70-90% if the vaccine strains match the circulating virus strains.

Relevance. The emergence of a new SARS-COV-2 coronavirus in early 2020 radically changed the seasonal pattern of influenza and other acute respiratory infections worldwide. Along with a decrease in the frequency of RSV infection, the number of diagnosed cases of influenza virus infection decreased by 99% during the COVID-19 pandemic. Vaccines are known to be the best tool at our disposal for preventing infectious diseases and reducing the risk of serious complications and deaths. The Russian Federation has great experience in developing vaccines against viral and bacterial infections and is constantly improving the technology of their production putting new vaccine preparations into circulation. Domestic vaccines against a new coronavirus infection caused by SARS-CoV-2 virus were developed in the shortest possible time. This work evaluated the efficacy of Gam-Covid-Vac (Sputnik V) and CoviVac vaccines during periods of circulation of different variants of SARS-CoV-2 «Delta» and «Omicron» in St. Petersburg. Aims. To evaluate the prophylactic efficacy of domestic vaccines Gam-Covid-Vac (Sputnik V) and CoviVac in the epidemic season 2021–2022 in the periods of SARS-CoV-2 «Delta» and «Omicron» variants circulation in Saint-Petersburg. Materials and Methods. Vaccination and follow-up of vaccinated subjects was initiated in February 2021, with the arrival of the Gam-Covid-Vac (Sputnik V) and CoviVac vaccines at the specialized clinic of Smorodintsev Research Institute of Influenza. Follow-up of vaccinated subjects for one year after vaccination included 346 men and women aged 19-85 years, who were interviewed in two telephone surveys. Results. Telephone interviews among individuals vaccinated with Gam-Covid-Vaс (Sputnik V) and CoviVac vaccines revealed that during the circulation of «Delta» variant, 2nd half of 2021, COVID-19 disease occurred in 16.3% of people vaccinated with the CoviVac vaccine and in 15.8% of those vaccinated with Sputnik V vaccine – differences between groups were not statistically significant (p > 0.05). COVID-19 disease in both vaccine groups was predominantly mild with 61.95% of observed falling ill in the CoviVac vaccine group and 84.4% (slightly more, 1.4-fold) in Sputnik V vaccine group. At the same time, moderate and severe diseases were slightly more in absolute value among those vaccinated with "CoviVac" vaccine. Cough, lung damage from 30% to 80%, loss of sense of smell and taste dominated among the symptoms in both groups of patients. During the second observation period (January-April 2022), when «Omicron» variant were actively circulating, the number of cases among CoviVac and Sputnik V vaccines was 37.5% and 43.8%, respectively; the differences between the vaccine groups were not statistically significant (p > 0.05). During this period, diseases in CoviVac and Sputnik V vaccine groups were predominantly mild in 84.4% and 90.5%, respectively, with statistically insignificant differences. There were also no significant differences in cases of moderate severity. Among those observed in « CoviVac» group during this period, a greater number of diseases, in absolute value, proceeding in a severe form and requiring hospitalization was noted. Clinically, the diseases caused by «Omicron» variant manifested in symptoms characteristic of flu and common cold: headache and muscle pain, fever, chills, chest pain, nasal congestion, severe fatigue, fatigue, weakness. Conclusions. During periods of active « Delta» variant circulation in the fall of 2021patients vaccinated with SARS-COV-2 coronavirus vaccines were 2.3 to 2.8 times less ill than during circulation periods of «Omicron» variants ВА.1 и ВА.2 in January-April 2022: 16.3% and 15.8%, 37.5% and 43.8%, respectively. Mild COVID-19 disease predominated among patients vaccinated with both vaccines during periods of circulation of «Delta» and «Omicron» variants. Differences in the manifestation of clinical symptoms of the disease in the periods of circulation of different strains were noted. It was shown that the vaccines against SARS-CoV-2 infection Gam-Covid-Vac (Sputnik V) and CoviVac do not protect 100% against the disease, but protect against a severe course of the disease and lethal outcomes.

Causing millions of cases worldwide every year, influenza is one of the most common respiratory infections. The effectiveness of influenza vaccination and the nature of the resulting immune response may vary depending on the vaccine composition and age group. Since children are at the highest risk of disease and act as the main carriers of influenza, the assessment of the immunological efficacy of vaccines in this group is crucial for controlling the epidemic. Therefore, this study aimed to evaluate the characteristics of the humoral immune response in children after immunization with various types of inactivated influenza vaccines. An observational study was conducted in the 2019-2020 season and involved 230 children (< 18 years old) and a comparison group of 87 adults aged 18 to 60 years. The subjects, who provided informed consent to participate, were vaccinated with one of three vaccines (Grippol Plus, Sovigripp, or Ultrix) in an open-label fashion. The humoral immune response was assessed by measuring the hemagglutination inhibition (HI) titer in the paired sera taken before and three weeks after vaccination. The immunogenicity of the vaccines in the age group under 18, met the CPMP criteria for the assessment of inactivated influenza vaccines in terms of the fold increase in antibody titers and the proportion of individuals with seroconversion to all three components (A/H1N1pdm09, A/H3N2, and B/Victoria). Although 6 to 18-year-old participants showed a more robust immune response to the B/Victoria component compared to the adult participants (aged 18 to 60), it was insufficient to ensure that 70% of the participants have a protective antibody titer. A comparative analysis of the vaccines’ immunogenicity was carried out for a subgroup of children aged 6-18 who had initially low antibody levels at the time of vaccination. The analysis showed that the split vaccine Ultrix outperformed the adjuvanted vaccine Grippol Plus in generating an antibody response to the component B/Victoria; however, the antibody responses to the A/H1N1pdm09 and A/H3N2 components did not differ between the two vaccines. The children under 6 years of age demonstrated a less pronounced humoral immune response to vaccination compared with the other age groups, which may be due to the age-related characteristics of the immune system in children of preschool age.

Background. The vaccine is the best available instrument to prevent influenza and reduce the risks of major disease complications and mortality. The vaccine effectiveness during the influenza season depends on a number of factors: (1) a person vaccinated (their age and health status); (2) the vaccine formulation; (3) types and subtypes of the circulating viruses; (4) vaccination timeline, as the immune response fades over time. An influenza vaccine can yield different effectiveness in people who have been infected or vaccinated previously and in those who have not been yet exposed to the circulating viruses. At present, trivalent and quadrivalent influenza vaccines are registered and produced in Russia. It allows for vaccination of all social groups, including high-risk populations, and for increasing the number of vaccinated individuals yearly. Russian Federation constantly improves the production of influenza vaccines, introducing new variants of vaccine formulations into national clinical usage. It is thus essential to monitor and analyze the changes in the effectiveness of influenza vaccines every season.Aim of the study. To evaluate of the effectiveness of Russian domestic influenza vaccines during the epidemic season 2019–2020 in St. Petersburg compared to the season 2018–2019.Materials and Methods. 3315 female and male adult participants aged 18 years and older were monitored from October 2019 to March 2020. The group included university students and tutors, researchers, and production and office workers of industrial enterprises. Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri influenza vaccines were used for immunization.Results and Discussion. In the context of incomplete correspondence between the viruses circulating in Russia and the strains used in the vaccines, the vaccination of the St. Petersburg population during the epidemic season 2019-2020 with Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri influenza vaccines cumulatively reduced influenza and ARI incidences by half; the total vaccine effectiveness against influenza and ARI amounted to 50.0%. The strongest preventive effect was identified for Grippol Plus, Ultrix, and Ultrix Quadri which demonstrated the total vaccine effectiveness from 70.6% to 75.0%, and their effectiveness against influenza A and B viruses reached from 65.5% to 83.5%.Conclusion. In the context of incomplete correspondence between the viral strains used in the vaccines and the strains circulating in Russia and St. Petersburg during the epidemic season 2019- 2020 and considering the active circulation of non-influenza viruses such as rhinoviruses and adenoviruses, we found a moderate preventive effectiveness of the influenza vaccines during the seasonal epidemic increase in ARI cases. Russian domestic influenza vaccines were shown to have good acceptability, be safe, and non-reactogenic.

Background. The influenza vaccination coverage has steadily increased in the Russian Federation. The introduction of new domestic influenza vaccines into practice and the study of their effectiveness are of great importance for public health. However, a systematic analysis of the effectiveness of vaccines manufactured and used in Russia in recent years has not been performed. The aim ofthe study was to assess the epidemiological effectiveness of three domestic influenza vaccines in St. Petersburg during the 2018–2019 epidemic season.Material and methods. The organized community of 1892 young students aged 18 to 23 years has been under supervision during the period of time from October 2018 to March 2019. Influenza vaccines Grippol Plus, Sovigripp, and Ultrix were used for vaccination.Results and discussion. Prophylactic vaccination with influenza vaccines Sovigripp, Grippol Plus and Ultrix in the fall of 2018 led to a decrease in the incidence of influenza and other acute respiratory infections (ARI) by a total of 1.6–3.8 times; a decrease in the incidence of influenza by 2.7–7.1 times; the total protective efficacy of vaccines against influenza and ARI was 52.4%, and against influenza, taking into account laboratory correction, 73.3%.Conclusions. Under the conditions of the viruses circulating in Russia and in St. Petersburg in the 2018–2019 epidemic season the strains introduced into the composition of influenza vaccines, domestic influenza vaccines were characterized by good tolerance, were safe, areactogenic and had a pronounced protective effect. If the viruses circulating in Russia and in St. Petersburg in the 2018–2019 epidemic season corresponded to the strains introduced into the composition of influenza vaccines, domestic influenza vaccines, showing good tolerance, safety and low reactogenicity, had a pronounced protective effect.

Objective: comparative open-label randomized study of the safety and efficacy of the drugs Alpha-glutamyl-tryptophan + Ascorbic acid + Bendazole («Cytovir-3«) and Umifenovir for prophylactic influenza and acute respiratory viral infectionsin children aged over 6 in organized groups.Materials and methods. 207 healthy children ≥6 years old of organized educational groups. According to study protocol they were divided into 2 groups: 102 children were randomizes to receive Alpha-glutamyl-tryptophan + Ascorbic acid + Bendazole (Сytovir-3, Group 1), capsules (JSC MBSPC «Cytomed«, Russia) while 105 children were randomizes to receive Umifenovir 100 mg (Group 2) capsules (Pharmstandart Leksredstva, Russia). The frequency of adverse reactions on drugs and adverse events was assessed while taking drugs and within 3 weeks after. Efficiency was assessed by calculate value of prophylactic efficiency index in comparison groups. Efficacy was analyzed on the basis of the comparative incidence of children included in the study with a total incidence in Saint-Petersburg.Results: the studied drugs showed a high safety profile and match preventive clinical efficacy against influenza and acute respiratory viral infections. Both drugs during prophylactic administration stimulated the production of secretory IgA. A tendency to a decrease in the incidence of acute respiratory viral infections in groups of children taking the studied drugs was revealed and compared with general indicators reflecting the integrated epidemic situation of influenza and other acute respiratory viral infections in Saint-Petersburg during the study. The data obtained allow us to recommend the use of the drug Alpha-glutamyl-tryptophan + Ascorbic acid + Bendazole («Сytovir-3«) (dosage form – capsules) for the prevention of respiratory diseases in organized children’sgroups during the period of seasonal increase in the incidence of influenza and acute respiratory viral infectionsin.

Aim: To compare the safety and prophylactic efficacy of Cytovir-3 and Arbidol in an open-label randomized clinical trial in children at seasonal risk of infectious respiratory disease.Methods: This study was performed in the period preceding a seasonal outbreak of acute respiratory viral infections (ARVI) and influenza. The study enrolled apparently healthy children aged 6 to 18 years without contra-indications to either Cytovir-3 or Arbidol. Cytovir-3 was given as 1 capsule per day, each day in a fasted state for 12 days. Arbidol was taken as a 100 mg capsule twice a week for three weeks. Following dosing, subjects were followed-up for a further three weeks. Overall health and presence of symptoms of either ARVI or influenza were monitored daily in all subjects. The level of sIgA in saliva was baselined before treatment and measured at the end of the follow-up period.Results: Most subjects did not exhibit any change in overall health status during the dosing and follow-up periods. The first two cases of illness in subjects receiving Cytovir-3 were diagnosed at the end of the third week after completion of dosing. In those subjects receiving Arbidol the first cases of illness were reported at the end of the second week following the end of prophylactic dosing. All patients displayed a significant increase in sIgA level at the end of the dosing period, but this was more pronounced in the Cytovir-3 group. Conclusion: The results of this comparative randomized clinical trial confirmed the safety and tolerability of both medications, and that the prophylactic efficacy of Cytovir-3 is equal to that of Arbidol.

In this multicenter double blind randomized clinical study with parallel groups conducted with 612 healthy volunteers, domestic influenza quadrivalent inactivated subunit vaccine Grippol® Quadrivalent safety, tolerability and immunogenicity was evaluated in comparison with seasonal trivalent vaccines, It was demonstrated that quadrivalent influenza vaccine Grippol® Quadrivalent possesses good tolerability, low reactogenicity, and has favorable safety profile similar to that for trivalent comparators. Besides, it was proven that quadrivalent influenza vaccine Grippol® Quadrivalent has same immunogenicity for three conventional strains and significantly exceeds trivalent comparators for missed influenza B strain.

Aim. The research was aimed at evaluating the reactogenicity, safety and immunogenicity of Flu-M inactivated split influenza vaccine. Materials and methods. The reactogenicity, safety and immunogenicity of the drug were studied in the course of a multicenter, double blind, comparative, randomized clinical trial of immunized volunteers aged between 18 and 60 (comparator - Vaxigrip inactivated split vaccine for influenza prevention). Results. Domestic Flu-M inactivated split influenza vaccine manufactured by St. Petersburg Research Institute of Vaccines and Sera features favorable tolerability, high safety profile and adequate immunogenicity which is consistent with that of Vaxigrip influenza vaccine. Conclusion. Flu-M inactivated split influenza vaccine manufactured by St. Petersburg Research Institute of Vaccines and Sera can be recommended for authorization in the Russian Federation for the purpose of specific prophylaxis of influenza for adults aged between 18 and 60.

Over last years, a novel strategy for vaccination of people against potentially pandemic influenza A viruses is actively developed worldwide, i.e., a combined (prime-boost) vaccination. It provides amplification (boosting) of immune response for a vaccine be means of pre-vaccination (priming) with another vaccine. We have first studied an issue of immunological consequences for people after priming by live attenuated influenza H5N2 vaccine (LAIV), followed by a boost with inactivated influenza H5N1 vaccine (IIV) 1.5 years later. Unlike non-primed volunteers, the primed persons developed more rapid and high production of serum antibodies (of HAI-, MN-, ELISA-types) after a single vaccination with H5N1 IIV. That concerned induction of antibodies to the H5N1 vaccinal strain A, and other heterologous strains containing H5 haemagglutinin. In primed persons, the antibodies showed higher avidity as compared to non-primed individuals. Before inoculation with H5N1 IIV, the IgG-antibody titers to A virus (H5N1), and the levels of specific CD4+ and CD8+ memory T-cells proved to be higher in primed subjects than in non-primed persons. The boosting effect of H5N1 IIV did not correlate with HAI-and MN-based data on immunogenicity of priming H5N2 live attenuated vaccine. In general, the results obtained justify a new direction in applications of LAIVs for protection against potentially pandemic influenza virus A.

There are many data worldwide which suggest that the methods for evaluation of influenza vaccines immunogenicity should be improved. The only method validated in Russia is a HAI (haemagglutination inhibition) assay with serum samples from vaccinated volunteers. This assay does not, however, completely reflect the vaccine-induced immunological changes. In this study, we evaluated antibody immune responses to A (H5N1) inactivated influenza vaccine boosting in healthy volunteers previously primed with A (H5N2) live attenuated influenza vaccine. We compared three methods of antibody detection: (i) HAI assay with serum samples; (ii) ELISA with serum samples; (iii) ELISA with PBMC (peripheral blood mononuclear cells) culture supernates, i.e., an alternative test based on quantification of antibodies secreted by PBMC in vitro. The latter test was shown to have an advantage over other techniques in IgA and IgG antibody detection at early timepoints (day 7) after vaccination. The first two methods allowed immunogenicity assessment at day 28 after vaccination.Thus, a test based on antibody quantification in PBMC supernatant samples can be used as an alternative method for evaluation of influenza vaccines immunogenicity. This method also exhibits a better strainspecificity.

Respiratory viral infections of non-flu etiology – adenoviral infection, paraflu, RS-vioral infection etc. – account for the major share of SARS, up to 90%. The frequency of flu viruses infection makes up about 15% (type A – 12%, type B – 3%), paraflu viruses – up to 50%, adenoviruses – from 5 to 10%, RS-viruses – 4%, mycoplasma – 2.7%, enteroviruses – 1.2%. Combined infections make up about 23% of cases [1].

Respiratory viral infections of non-flu etiology – adenoviral infection, paraflu, RS-vioral infection etc. – account for the major share of SARS, up to 90%. The frequency of flu viruses infection makes up about 15% (type A – 12%, type B – 3%), paraflu viruses – up to 50%, adenoviruses – from 5 to 10%, RS-viruses – 4%, mycoplasma – 2.7%, enteroviruses – 1.2%. Combined infections make up about 23% of cases [1].

Pregnant women are at high risk for the adverse course of respiratory diseases, among which the influenza is the one of the leading infections, of ten finishing tragically for most pregnant and her offspring. Due to the disproportionately high morbidity, mortality and adverse outcomes of pregnancy after influenza virus infection, pregnant females are classified as a priority group for vaccination. Immunization with inactivated influenza vaccine is one of the most important strategy to prevent both of influenza infection, its severe complications, and mitigating of the effects of the epidemic of influenza. There was accumulated sufficient evidence demonstrating that the vaccine promotes the diminution of clinical manifestations of influenza infection in pregnant women, as well, has a positive effect on the health of the newborns due to the active transport of maternal antibodies. In the review there are presented data on the safety, high immunogenicity and clinical efficacy of vaccination against influenza as for pregnant women as well for infants.

Interferon-gamma (IFN-y) is a pleiotropic lymphokine that have multiple effects on the growth and differentiation of various types of cells associated with innate immunity. IFN-y induces differentiation ofmyeloid cells, stimulates the expression of major histocompatibility complex (MHC) class II and class I antigens, it is a potent activator of macrophages which destroy antigenic molecules penetrating the cell. IFN-y is widely used for the treatment of infectious diseases, cancer, autoimmune and allergic diseases. Studies conducted in Research Institute ofInfluenza indicate that drugs IFN-y can be successfully usedfor prevention of influenza and acute respiratory infection (ARI) during the rise of incidence, as well as for the treatment - the first few days/ hours of the onset. The concomitant use of drugs as IFN-a and IFN-y on influenza and ARI can greatly improve the prophylactic and therapeutic efficacy.

From the beginning of 21th century outbreaks of H5, H7 and H9 avian flu are registered from time to time. These viruses are considered as one of the possible causes of the next pandemia. The development of avian influenza vaccines is one of the WHO priorities. The aim of this work was to study antibody and cellular immune responses to avian A (H5N2) and A (H7N3) live attenuated influenza vaccines (LAIVs). We examined serum antibodies (HAI assay, microneutralization assay, ELISA), local antibodies (ELISA) and virus-specific CD4+ and CD8+ central memory and effector memory T cells. Two doses vaccination of healthy volunteers with A (H5N2) and A (H7N3) LAIVs induced homological antibody and cellular immune responses (i. e. serum and local antibody conversions, virus-specific memory T cell growth). These vaccines also stimulated heterological immunity (heterological serum and local antibodies and T cells). Heterological immune response intensity depended on antigenic structure of vaccine strain and heterological virus, particularly on HA type.

Currently, application of new technological solutions for the implementation of strategies for improving influenza vaccines are up to date and modern. In this study, we present data obtained in the evaluation of the safety and immunogenicity of the new Russian (national) split seasonal inactivated influenza vaccine ULTRIKS in comparison with a commercial vaccine VAXIGRIP in various age groups.

Abstract. Evaluation of reactogenicity, safety and immunogenicity of the inactivated subunit influenza vaccine adsorbed monovalent (Pandeflu) on the base of strain A/California/7/2009 (H1N1v) was conducted in 70 volunteers aged 18–60 years immunized by one or two doses. A clinical trial of the vaccine Pandeflu was conducted in the St.Petersburg Institute of Influenza. The study group included 38 women (54,3%) and 32 men (45,7%). The average age of women was 38.2 years, men — 26.9 years, mean age of all volunteers was equal to 31.7 years. This group of volunteers was randomized in 2 subgroups. The first subgroup of 50 volunteers was vaccinated with Pandeflu, but the second one of 20 volunteers was given a placebo. The strong and moderate local and systemic reactions were not observed. All local (6 volunteers) and systemic (6 volunteers) reactions were recorded after ithout any medical care. It proves the good tolerability and low reactogenicity of vaccine Pandeflu. Indicators of clinical and biochemical blood tests, a general analysis of urine during the study period were within normal limits. In the study of the immunogenicity it has been shown that after a single injection of vaccine the first vaccination. All these reactions were mild and transient and disappeared wPandeflu the seroconversion rate reached 68%, but the level of seroprotection was 52%. The multiplication factor of the geometric mean antibody titer increase in serum reached a value of 5.8. Conducting of immunization with two doses of vaccine with the interval of 28 days increases the immunogenicity: the level of seroconversion rate increases up to 96%, but the level of seroprotection – up to 74%, seroconversion factor – up to 10.8. These data confirm high immunogenic potential vaccine in case of single dose as well as double doses administration.