Introduction: The development of bivalent mucosal vaccines capable of providing protection against both influenza and SARS-CoV-2 is a major public health focus. While most COVID-19 vaccines target the spike (S) protein, the highly conserved nucleocapsid (N) protein represents a strategic target for cross-reactive, cell-mediated immunity. This study evaluates Corfluvec, an intranasal vaccine candidate based on an attenuated NS1-truncated influenza vector expressing a fragment of the SARS-CoV-2 N protein. Methods: Protective efficacy, including viral load and pathomorphological changes in the lungs and vessels, was evaluated in Syrian hamsters challenged with high and low doses of SARS-CoV-2 (lineage B.1.1). Cross-protective efficacy against homologous and heterologous influenza A strains (H1N1pdm09, H3N2, and A/PR/8/1934) was tested in a lethal murine model. Additionally, immunogenicity of Corfluvec applied via human-compatible delivery device was tested in cynomolgus macaques (Macaca fascicularis). Results: In Syrian hamsters, vaccination significantly reduced viral loads in the lungs and nasal turbinates. Histopathological analysis revealed a preservation of lung vascular integrity: vaccinated animals showed stable CD31 expression and controlled Ki-67 proliferative activity, accompanied by a marked reduction in vasculitis and perivascular edema compared to placebo controls. In mice, the vaccine provided 100% protection against homologous and heterologous influenza virus challenges. In macaques, the two-dose intranasal immunization was well-tolerated and induced significant systemic IgG and mucosal sIgA responses, alongside robust N-specific IFNγ+ T-cell activation. Conclusions: Corfluvec is a promising bivalent vaccine candidate that provides dual protection against influenza and COVID-19. Its ability to limit viral shedding from the upper respiratory tract and to mitigate SARS-CoV-2-induced pulmonary pathology, contributing to the preservation of lung vascular integrity, underscores the utility of mucosal immunization with Corfluvec as a valuable intranasal complement to current systemic vaccination strategies.
Background: Patients with end-stage renal disease (ESRD) on hemodialysis are at increased risk for severe influenza, and underlying immune dysfunction may limit vaccine-induced protection. Methods: This observational open-label study evaluated immune responses in 93 hemodialysis patients vaccinated with seasonal inactivated influenza vaccine (IIV) during the 2019–2020 (n = 22) and 2023–2024 (n = 71) seasons. Immune responses were comprehensively assessed using hemagglutination inhibition and microneutralization assays to measure antibody levels, together with flow cytometry analysis of key immune cell populations, including plasmablasts, T-follicular helper cells (Tfh), and effector memory T cells (Tem). Results: During the 2019–2020 season, antibody responses in hemodialysis patients were comparable to those in healthy volunteers in both younger (18–60 years) and older (over 60) age groups. By day 7 post-vaccination, there was a pronounced increase in activated Tfh1 cells, coinciding with a surge in plasmablasts and a rise in antigen-specific B cells. This was accompanied by a T-cell response mediated by IFNγ-producing and polyfunctional CD4+ Tem cells. In the 2023–2024 season, revaccination was associated with higher baseline antibody levels but did not alter subsequent response kinetics to A/H1N1pdm, A/H3N2, and B/Yamagata antigens. In contrast, responses to B/Victoria were higher in revaccinated patients throughout the entire observation period. Conclusions: Our findings confirm that standard-dose IIV vaccination is beneficial for hemodialysis patients, inducing robust and adequate humoral and T-cell immune responses.
Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at the primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are a promising vaccine approach that ensures a pronounced local CD8+ T-cellular immune response. Here, we describe the protective and immunomodulating properties of an influenza vector FluVec-N carrying the C-terminal fragment of the SARS-CoV-2 nucleoprotein within a truncated NS1 open reading frame. Methods: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector’s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve mice and seropositive Th2-prone mice, primed with aluminium-adjuvanted inactivated SARS-CoV-2. Immune response in immunized and challenged mice was analyzed through serological methods and flow cytometry. Results: Double intranasal immunization of naïve mice with FluVec-N reduced weight loss and viral load in the lungs following infection with the SARS-CoV-2 beta variant. Mice primed with alum-adjuvanted inactivated coronavirus experienced substantial early weight loss and eosinophilia in the lungs during infection, demonstrating signs of enhanced disease. A single intranasal boost immunization with FluVec-N prevented the disease enhancement in primed mice by modulating the local immune response. Protection was associated with the formation of specific IgA and the early activation of virus-specific effector and resident CD8+ lymphocytes in mouse lungs. Conclusions: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology.
Background Rapid vaccine platforms development is crucial for responding to epidemics and pandemics of emerging infectious diseases, such as Ebola. This study explores the potential of peptide vaccines that self-organize into amyloid-like fibrils, aiming to enhance immunogenicity while considering safety and cross-reactivity. Methods We synthesized two peptides, G33 and G31, corresponding to a segment of the Ebola virus GP2 protein, with G33 known to form amyloid-like fibrils. Their toxicity was assessed in vitro using an MTT assay on MDCK and A549 cell cultures. For in vivo studies, balb/c mice were immunized with these peptides. Immunogenicity was gauged by ELISA for specific antibodies against the recombinant eGP protein. Hematological parameters were determined, and histopathological changes in organs were documented post-euthanasia. Results Both peptides exhibited no cytotoxicity up to 500 μg/mL. G33-immunized mice developed higher antibody titers than those receiving G31 or control, without significant alterations in hematological profiles. However, histological analysis showed periportal infiltration and lymphoid-macrophage clusters in the liver and kidneys, suggesting immune response activation. The homology between the G33 peptide and mammalian proteins poses risks of cross-reactivity. Conclusion The amyloid-like fibrils formed by the G33 peptide elicited a stronger immune response without significant hematological changes, underlining the feasibility of fibril-based peptide vaccines. However, the potential for autoimmune responses due to molecular mimicry warrants further investigation before clinical applications can be considered.
Patients with End-Stage Renal Disease on hemodialysis (HD) are at high risk for severe influen-za, and their underlying immune dysfunction may limit the magnitude of vaccine-induced pro-tection. This observational study evaluated the immune response in 93 hemodialysis patients vaccinated with the seasonal inactivated influenza vaccine (IIV) across the 2019-2020 (n=22) and 2023-2024 (n=71) seasons. Immune response was comprehensively assessed by measuring hemagglutina-tion inhibition (HAI) and neutralizing antibody titers and by analyzing the frequencies of key immune cells, including plasmablasts, T-follicular helper cells (Tfh), and effector memory T cells (Tem). The results of observation in 2019-2020 showed that the antibody response in HD patients was comparable to that of healthy volunteers, including both younger (18-60) and older (over 60) age groups. By day 7, there was a pronounced increase in activated Tfh1 cells, a corresponding surge in plasmablasts, and a rise in antigen-specific B-cells. A T-cell response followed, mediated by IFNγ-producing and polyfunctional CD4+ effector memory T cells. Subsequent vaccination in 2023-2024 season determined a higher baseline level of the antibody response but did not affect its further dynamics in case of A/H1N1pdm, A/H3N2, B/Yamagata virus antigens. The response to B/Victoria was higher in the revaccinated group throughout the entire observation period. Our findings confirm that standard-dose IIV vaccination is beneficial for HD patients, inducing a robust and compliant humoral and T-cell immune response that is not inferior to that of the general population.
The paper presents the results of modeling the effect of an additional magnetizing field on the parameters of the shield of an onboard rubidium atomic clock. On a laboratory setup, under conditions of the effect of a rotating magnetic field on the clock, simulating the magnetic environment on satellite board, the dependences of the Allan deviation of the rubidium atomic clock frequency were obtained. The studies were carried out for different values of the magnetizing field oriented coaxially and perpendicularly to the optical axis of the clock. The parameters of the magnetizing field for the amplitude of the rotating magnetic field of 2.4 A/m, 4.8 A/m and 24 A/m, corresponding to high, medium and low orbits of satellites, were specified. Also, a numerical modeling of the magnetic field effect on the parameters of the atomic clock magnetic shield was performed, showing the efficiency of using the magnetizing field in low geomagnetic fields. Calculations of the shielding factor of a single-layer magnetic shield in the function of a magnetizing magnetic field are carried out and a close correspondence of this dependence to the dynamics of the longitudinal shielding coefficient measured in a model experiment with a two-layer magnetic shield of an atomic clock is noted.
The Russian Federation has high level of social protection coverage. However, for the population that is part of the labor force, coverage of key types of social security is provided mainly through social insurance. The inclusion of citizens (as insured) in compulsory social insurance is a subject for payment of insurance premiums in their favor by employers (as insurers). Against the background of the growing involvement of the Russian population in new, non-standard forms of employment, there is an outflow of the employed population from the sphere of labor relations with social guarantees enshrined in labor legislation, into the sphere of civil law relations and even into shadow employment, as a result of which there is a risk of a shortage of social security for the economically active population. The aim of the study to assess the existing deficit of social security in Russia for workers in new forms of employment, that is carried out using legal and sociological approaches. The results of the study indicate a connection between the shortage of social security of the population employed in new forms with the lack of conscious interest among citizens in participating in insurance of possible social risks in the future, as well as the current need to purchase insurance protection at their own expense. During the transformation of the labor market and the active influx of the population into new forms of employment (including through the transition from labor relations to self-employment and entrepreneurship), the absence of a market insurance culture does not automatically lead to a redistribution of responsibility between participants in the social protection system. With a decrease in the number of employers and a consequent decrease in social protection spending, the demand for social insurance services among the population has not yet been formed. In many ways, this is due to the unwillingness of the self-employed population to lose part of their income (forming “deferred consumption”). If we turn to the figures of the average income of the self-employed, their behavior is largely understandable. In these circumstances, the problem of providing social security to the population intersects with the problem of combating poverty and low income. On the other hand, the obligations of the Russian government to provide the population with social security are enshrined in the Constitution of the Russian Federation. The decrease in participants in pension and social insurance programs today leads to a gradual increase in the deficit of the social security budget in the future, in which it will become increasingly difficult to fulfill these obligations. It can be assumed that this is one of the main reasons determining the government’s interest in expanding activity in relation to social protection policy. At the same time, employees of new forms of employment, guided more by the value of “earning now”, do not show significant interest in voluntary insurance programs. In such a situation, it is possible to assume an increase in the gap between the satisfaction/sense of security of workers in new forms of employment and their growing anxiety about the social policy being implemented in the country. To conclude, Russia is currently in a “transitional stage”, when an active search is underway for a balance between legal access to social protection and demand for specific areas of social protection that requires gradual, careful work on the part of the state, with consultations with “new social partners” (for example, digital labor platforms and platform workers), as well as the selfemployed and their associations. In this context, the development of new instruments of social partnership and state regulation of social protection mechanisms for the population involved in new forms of employment seems to be an important and priority task in the near future.
In the paper, the results of a study of the influence of the magnetic shield magnetization on the relative frequency instability of small-sized rubidium atomic clocks have been presented. The atomic clock was placed in a rotating magnetic field, simulating the magnetic situation in the orbit of a navigation satellite, moving in orbit and rotating around its own axis. The magnetization of the magnetic shield of the atomic clock was shown to increase its shielding factor. This result makes it possible to significantly reduce the influence of geomagnetic field variations on the frequency stability of onboard atomic clocks.
One of the ways to regulate the sensitivity of human cells to the influenza virus is to knock out genes of the innate immune response. Promising targets for the knockout are genes of the interferon-inducible transmembrane protein (IFITM) family, in particular the IFITM3 gene, whose product limits the entry of a virus into the cell by blocking the fusion of the viral and endosomal membranes. In this study, by means of genome-editing system CRISPR/Cas9, monoclonal cell lines with an IFITM3 knockout were obtained based on WI-38 VA13 cells (human origin). It was found that such cell lines are more sensitive to infection by influenza A viruses of various subtypes. Nevertheless, this feature is not accompanied by an increased titer of newly formed viral particles in a culture medium.
Background/Objectives: Humoral immunity directed against neuraminidase (NA) of the influenza virus may soften the severity of infection caused by new antigenic variants of the influenza viruses. Evaluation of NA-inhibiting (NI) antibodies in combination with antibodies to hemagglutinin (HA) may enhance research on the antibody response to influenza vaccines. Methods: The study examined 64 pairs of serum samples from patients vaccinated with seasonal inactivated trivalent influenza vaccines (IIVs) in 2018 according to the formula recommended by the World Health Organization (WHO) for the 2018–2019 flu season. Antibodies against drift influenza viruses A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09 and A/Brisbane/34/2018(H3N2) were studied before vaccination and 21 days after vaccination. To assess NI antibodies, we used an enzyme-linked lectin assay (ELLA) with pairs of reassortant viruses A/H6N1 and A/H6N2. Anti-HA antibodies were detected using a hemagglutination inhibition (HI) test. The microneutralization (MN) test was performed in the MDCK cell line using viruses A/H6N1 and A/H6N2. Results: Seasonal IIVs induce a significant immune response of NI antibodies against influenza A/H1N1pdm09 and A/H3N2 viruses. A significantly reduced ‘herd’ immunity to drift influenza A/H1N1pdm09 and A/H3N2 viruses was shown, compared with previously circulating strains. This reduction was most pronounced in strains possessing neuraminidase N2. Seasonal IIVs caused an increase in antibodies against homologous and drifted viruses; however, an increase in antibodies to drifting viruses was observed more often among older patients. The level of NI antibodies for later A/H1N1pdm09 virus in response to IIVs was statistically significantly lower among younger people. After IIV vaccination, the percentage of individuals with HI antibody levels ≥ 1:40 and NI antibody levels ≥ 1:20 was 32.8% for drift A/H1N1pdm09 virus and 17.2% for drift A/H3N2 virus. Antisera containing HI and NI antibodies exhibited neutralizing properties in vitro against viruses with unrelated HA of the H6 subtype. Conclusions: Drift A/H1N1pdm09 and A/H3N2 viruses demonstrated significantly lower reactivity to HI and NI antibodies against early influenza viruses. In response to seasonal IIVs, the level of seroprotection has increased, including against drift influenza A viruses, but protective antibody levels against A/H1N1pdm09 have risen to a greater extent. A reduced immune response to the N1 protein of the A/H1N1pdm09 drift virus was obtained in individuals under 60 years of age. Based on our findings, it is hypothesized that in the cases of a HA mismatch, vaccination against N1-containing influenza viruses may be necessary for individuals under 60, while broader population-level vaccination against N2-containing viruses may be required.
Influenza A and B viruses are widely spread respiratory pathogens of humans and cause both isolated cases and local outbreaks of the disease, as well as massive seasonal epidemics and pandemics. Vaccination is the main strategy for combating influenza, and an increase in the proportion of vaccinated people in the population determines the success of vaccination. To identify patterns of postvaccination immune response formation to different types of vaccines and assess the significance of its multiple parameters the appropriate statistical methods should by applied. These methods allow to operate with large datasets and reduce their dimension, while keeping the maximum of information about the differences between individual observations. The aim of our study was the analysis of parameters of humoral and cellular immunity and their dynamics after vaccination with different types of inactivated influenza vaccines (IIV) using statistical methods of complex data analysis. The study was conducted in the clinical department of the Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, in the flu season 2018 – 2019. The multivariate analysis of the immune response parameters after immunization with IIV “Grippol plus”, “Sovigripp” “Ultrix” included data obtained for 39 volunteers before vaccination, on the 7th and 21st days after vaccination. To identify parameters with significant differences between groups, one-factor analysis of variance (ANOVA) was used separately for each parameter and time point. To visualize the differences in the parameters selected in the analysis of variance, the Principal component analysis (PCA) method was used. The conducted studies revealed the peculiarities of the formation of a post-vaccination immune response to various types of IIV. It was shown that the factors of antigen-specific CD4+ and CD8+ T-cell immune response introduced the major contribution to the formation of the differences between groups. The approach is a powerful tool in analyzing the parameters of the immune response in clinical trials of influenza vaccines and other preventive medicine.
The paper analyzes the effect of geomagnetic variations on the results of measuring the coordinates of a moving point magnetic dipole using signals from a laboratory quantum gradiometer in the form of two M Z -type quantum magnetometers with an optical lamp pumping. It is shown that geomagnetic field variations within the laboratory are random and do not depend on the location coordinates of the magnetometers. In addition, the paper discusses the proposed method for determining the distance from the sensitive magnetometer sensor to the magnetic dipole.
Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties. While escape from humoral immunity certainly contributes to intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin’s lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented the binding of known immunogenic SARS-CoV-2 HLA class I antigens. By experimentally assessing the effect of a subset of the escape mutations, we show that they resulted in a loss of as much as ~1% of effector CD8 T cell response. Our results indicate that CD8 T cell escape represents a major underappreciated contributor to SARS-CoV-2 evolution in humans.
Intranasal vaccination using influenza vectors is a promising approach to developing vaccines against respiratory pathogens due to the activation of the mucosa-associated immune response. However, there is no clear evidence of a vector design that could be considered preferable. To find the optimal structure of an influenza vector with a modified NS genomic segment, we constructed four vector expressing identical transgene sequences inherited from the F protein of the respiratory syncytial virus (RSV). Two vectors were designed aiming at transgene accumulation in the cytosol. Another two were supplemented with an IgGκ signal peptide prior to the transgene for its extracellular delivery. Surprisingly, adding the IgGκ substantially enhanced the T-cell immune response to the CD8 epitope of the transgene. Moreover, this strategy allowed us to obtain a better protection of mice from the RSV challenge after a single intranasal immunization. Protection was achieved without antibodies, mediated by a balanced T-cell immune response including the formation of the RSV specific effector CD8+ IFNγ+/IL10+-producing cells and the accumulation of Treg cells preventing immunopathology in the lungs of infected mice. In addition to the presented method for optimizing the influenza vector, our results highlight the possibility of achieving protection against RSV through a respiratory-associated T-cell immune response alone.
We report the genomic analysis of a highly divergent SARS-CoV-2 sample obtained in October 2022 from an HIV+ patient with presumably long-term COVID-19 infection. Phylogenetic analysis indicates that the sample is characterized by a gain of 89 mutations since divergence from its nearest sequenced neighbor, which had been collected in September 2020 and belongs to the B.1.1 lineage, largely extinct in 2022. 33 of these mutations were coding and occurred in the Spike protein. Of these, 17 are lineage-defining in some of the variants of concern (VOCs) or are in sites where another mutation is lineage-defining in a variant of concern, and/or shown to be involved in antibody evasion, and/or detected in other cases of persistent COVID-19; these include some “usual suspects,” such as Spike:L452R, E484Q, K417T, Y453F, and N460K. Molecular clock analysis indicates that mutations in this lineage accumulated at an increased rate compared to the ancestral B.1.1 strain. This increase is driven by the accumulation of nonsynonymous mutations, for an average dN/dS value of 2.2, indicating strong positive selection during within-patient evolution. Additionally, there is reason to believe that the virus had persisted for at least some time in the gastrointestinal tract, as evidenced by the presence of mutations that are rare in the general population samples but common in samples from wastewater. Our analysis adds to the growing body of research on evolution of SARS-CoV-2 in chronically infected patients and its relationship to the emergence of variants of concern.
The paper presents the results of modeling the correction of small-sized onboard rubidium atomic clock according to the signal of a quantum magnetometer, the readings of which exactly correspond to variations in the external magnetic field installed near the onboard atomic clock and registering both the magnitude and direction of the geomagnetic field in a moving carrier. Various variants of modulation of the external magnetic field are considered and the time dependences of the Allan deviation for these variants are constructed. The correlation coefficients corresponding to variations in the frequency of atomic clock and the readings of a quantum magnetometer are calculated, and the possibility of compensating fluctuations in the frequency of atomic clock caused by a change in the orientation of the carrier in geomagnetic space is demonstrated.
Inactivated vaccines are promising tools for tackling the COVID-19 pandemic. We applied several protocols for SARS-CoV-2 inactivation (by β-propiolactone, formaldehyde, and UV radiation) and examined the morphology of viral spikes, protein composition of the preparations, and their immunoreactivity in ELISA using two panels of sera collected from convalescents and people vaccinated by Sputnik V. Transmission electron microscopy (TEM) allowed us to distinguish wider flail-like spikes (supposedly the S-protein’s pre-fusion conformation) from narrower needle-like ones (the post-fusion state). While the flails were present in all preparations studied, the needles were highly abundant in the β-propiolactone-inactivated samples only. Structural proteins S, N, and M of SARS-CoV-2 were detected via mass spectrometry. Formaldehyde and UV-inactivated samples demonstrated the highest affinity/immunoreactivity against the convalescent sera, while β-propiolactone (1:2000, 36 h) and UV-inactivated ones were more active against the sera of people vaccinated with Sputnik V. A higher concentration of β-propiolactone (1:1000, 2 h) led to a loss of antigenic affinity for both serum panels. Thus, although we did not analyze native SARS-CoV-2 for biosafety reasons, our comparative approach helped to exclude some destructive inactivation conditions and select suitable variants for future animal research. We believe that TEM is a valuable tool for inactivated COVID-19 vaccine quality control during the downstream manufacturing process.
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.
The major protective immune response against viruses is production of type I and III interferons (IFNs). IFNs induce the expression of hundreds of IFN-stimulated genes (ISGs) that block viral replication and further viral spread. The ability of respiratory viruses to suppress induction of IFN-mediated antiviral defenses in infected epithelial cells may be a factor contributing to the particular pathogenicity of several strains. In this report, we analyzed expression of IFNs and some ISGs in an alveolar epithelial cell subtype (A549) in response to infection with: influenza A viruses (A/California/07/09pdm (H1N1), A/Texas/50/12 (H3N2)); influenza B virus (B/Phuket/3073/13); adenovirus type 5 and 6; or respiratory syncytial virus (strain A2). IFNL and ISGs expression significantly increased in response to infection with all RNA viruses 24 hpi. Nevertheless, only IBV led to early increase in IFNL and ISGs mRNA level. IBV and H1N1 infection led to elevated proinflammatory cytokine production. We speculate that augmented IFN-α, IFN-β, IL-6 levels negatively correlate to SOCS1 expression. Importantly, we showed a decrease in IFNLR1 mRNA in case of IBV infection that implies the existence of negative ISGs expression regulation at IFNλR level. It could be either a specific feature of IBV or a consequence of early IFNL expression.
Neuraminidase (NA)-based immunity could reduce the harmful impact of novel antigenic variants of influenza viruses. The detection of neuraminidase-inhibiting (NI) antibodies in parallel with anti-hemagglutinin (HA) antibodies may enhance research on the immunogenicity and duration of antibody responses to influenza vaccines. To assess anti-NA antibodies after vaccination with seasonal inactivated influenza vaccines, we used the enzyme-linked lectin assay, and anti-HA antibodies were detected in the hemagglutination inhibition assay. The dynamics of the anti-NA antibody response differed depending on the virus subtype: antibodies to A/H3N2 virus neuraminidase increased later than antibodies to A/H1N1pdm09 subtype neuraminidase and persisted longer. In contrast to HA antibodies, the fold increase in antibody titers to NA after vaccination poorly depended on the preexisting level. At the same time, NA antibody levels after vaccination directly correlated with titers before vaccination. A difference was found in response to NA antigen between split and subunit-adjuvanted vaccines and in NA functional activity in the vaccine formulations.