The investigation of the dynamics of changes in neutralizing antibody titers against type 5 adenovirus in the context of vaccination against a new coronavirus infection.

This research focuses on analyzing the dynamics of neutralizing antibody (nAbs) titers against type 5 adenovirus (Ad5) in the adult population of Russia following vaccination against the novel coronavirus infection with recombinant adenovirus type-5 COVID-19 vaccine (CanSino Biologics, China). The impact of the Ad5 vector on nAb titers was investigated using 302 blood serum samples from individuals who received a single dose of the Ad5-nCoV vector vaccine. The research revealed that 33.8% of adults in Russia had pre-existing anti-Ad5 nAbs before the pandemic. Notably, 40% of vaccinated individuals did not exhibit an increase in nAbs titers upon receiving the Ad5-based vaccine. However, in the group with no or low titers of anti-Ad5 nAbs (1:10-1:40), a significant 8-16-fold increase in nAb titers to Ad5 was observed.

[The application of radial hemolysis technique in detection of antibodies to avian influenza virus A (H5N1) and pandemic virus A (H1N1) pdm09].

The article discusses the results of study that demonstrated the possibility of successful application of radial hemolysis reaction in analyzing the human inoculation immunity to new strains of influenza virus serotype A - A (H5N1) and A (H5N2). The radial hemolysis reaction provides accurate results on introduction of erythrocytes of horse or sheep into hemolytic system instead of erythrocytes of hens applied previously. The technique combines high sensitivity (in comparison with reactions of hemagglutination-inhibition and micro-neutralization, correlation coefficient 0.84-0.85) and total absence of inhibitors impact on the reaction results. During the investigation of immune response of patients who had pandemic virus A (H1N1) pdm09, radial hemolysis reaction demonstrated not only primary detection of antibodies to virus-agent (67%) during pandemic, but also elective heightened sensibility in the zone of low titer serums (1:20) in hemagglutination-inhibition reaction. These characteristics are very important in analysis of antibodies levels at early stages of disease. The radial hemolysis reaction continues to be a reliable instrument in evaluating qualitative and quantitative indicators of humoral immunity in ill patients and persons inoculated with new strains of human influenza virus.

[Development of competitive enzyme immunoassay for the detection of influenza A(H5) virus antibodies].

An indirect enzyme immunoassay (EIA) using the purified fraction of surface viral glycoproteins (GP) as an antigen for solid phase sensitization was not shown to be a specific method for the differential detection of influenza A(HS) (HS-Ab) virus antibodies (Abs) due to total conservative epitopes in the structure of GPs of influenza A(H5) and A(H1NI) viruses. The cross activity of some monoclonal Abs (MAbs) to influenza A(H5) and A(HIN1) viruses, which had been obtained at the Research Institute of Influenza, was proof of the presence of total immunodominant determinants in the structure of influenza H1 and H5 virus hemagglutinin (HA). In this connection, an EIA, which was based on the competition of influenza A(H5) H5-Ab virus HA-specific MAbs in the test sera for an association with influenza A(H5) virus, was proposed for the subtype-specific detection of H5 Ab. Comparison of the results of competitive EIA (cEIA), microneutralization (MN) test and HA inhibition test (HAIT) (using equine red blood cells) in the examination of sera obtained from 44 volunteers immunized with inactivated vaccine containing influenza A/Indonesia/5/2005 (H5N1) virus showed the high sensitivity and specificity of cEIA in detecting H5-specific Abs. The effectiveness of cEIA for the sera strictly positive for the content of H5 Abs was close to that of MN test and was 9-34% higher than HAIT (depending on those used in the analysis of H5 virus antigens). cEIA may be proposed to assess new influenza vaccines as an additional laboratory test. Since the infectious virus is not used during cEIA, it may be recommended for the serodiagnosis of influenza A(H5) at practical virological laboratories.

Studies on influenza-virus virulence in recombinants between epidemic and vaccine strains.

Influenza virus recombinants between epidemic strains A/Brazil/11/78 (H1N1), A/USSR/382/78 (H3N2) and vaccine strains A/Leningrad/9/46 (H1N1), A/Victoria/35/72/50 (H3N2) have been tested for virulence for humans and albino mice; their genome structure has also been determined. It has been shown that after the replacement of surface antigens of A/Leningrad/9/46 (H1N1) strain by surface antigens of A/Brazil/11/78 (H1N1) or A/USSR/382/78 (H3N2), strains, the virus becomes totally nonpathogenic for mice whereas its virulence for humans is enhanced. The combination in recombinant X/28 (H1N1) of haemagglutinin and neuraminidase of A/Brazil/11/78 (H1N1) virus and othercomponents of A/Leningrad/9/46 virus determines its high affinity to the epithelium of the upper respiratory tract of humans, as well as its marked virulence for seronegative volunteers. Genetic mechanisms of influenza virus virulence and the involvement of surface proteins in its specific manifestations are discussed. It has been shown that pathogenic properties and the affinity of the virus to particular tissues are determined by different genes and their reasortment can result in the appearance of essentially new properties in recombinants.

Search for optimal scheme for administering live allantoic influenza vaccine.

The effect of vaccine dilution and composition on indices of vaccination activity was studied in a live allantoic influenza vaccine administered intranasally to adults. The vaccine was shown to be usable in a 1:1 (instead of 1:5) dilution without risk of its reactogenicity rising. An inhibition of component A(H3N2) was observed in a bivalent vaccine obtained by combining directly before use two monovalent vaccines, A(H1N1) and A(H3N2). The conclusions and recommendations based on the results of the present study have practical implications in influenza control.

[Variability of the virulent properties of influenza A viruses in recombination]. / Izmenchivost' virulentnykh svoistv virusov grippa A pri rekombinatsii.

The pattern of redistribution of human virulence in epidemic strains of influenza viruses in recombination with human avirulent strains was studied. In the course of recombination of epidemic and attenuated influenza virus strains variants with different human virulence were obtained. Some recombinants manifested enforced reactogenic properties as compared with the epidemic strain (X/28, M/35, and 0/26--H1N1, and 2P--H3N2). At the same time, recombinants No 19 (H1N1) and 1P (H3N2) with a similar set of surface antigens were innocuous for man after intranasal administration. Using the observed differences in sensitivity to remantadine as a marker of recombination, we obtained several sets of recombinants which had the antigenic structure of surface proteins of epidemic viruses and remantadine sensitivity of the other parent.

[The course of the protective cellular reactions to the intraperitoneal administration of different influenza virus strains in newborn mice]. / Osobennosti techeniia zashchitnykh kletochnykh reaktsii pri vnutribriushinnom vvedenii novorozhdennym mysham razlichnykh shtammov virusa grippa.

The features of response of the macrophagal system in relation to the development of inflammatory reaction caused by PMN-leukocytes in response to intraperitoneal inoculation of newborn white mice with various influenza virus strains of different degrees of attenuation were studied. With the A2/Frunze/76 virus highly toxic for mice the protection was exerted mostly by neutrophils whereas the participation of macrophages in host resistance under these conditions was comparatively small. With the decline of inflammatory PMN-reaction upon intraperitoneal inoculation of A2/Leningrad/337/76 virus the number and functional activity of macrophages participating in the reaction increased. Within one strain, variants in low passage levels produced greater inhibition of acid phosphatase activity in macrophages as compared with highly passaged viruses. The increased resistance of the macrophage system appeared to prevent to a certain degree the development of inflammation and contributed to a decrease of the pathological process.