[Characterization of cold-adapted influenza strain A/HongKong/1/68/162/35 as a potential donor of attenuation and high reproduction].

Live and inactivated vaccines are currently produced using virus reassortants originating from various gene donors of internal proteins. Based on the pandemic virus A/Hong Kong/1/68 (H3N2), a cold-adapted thermo-sensitive strain A/Hong Kong/1/68/162/35 was generated. It is distinguished for its high reproductive capacity (9-9.5 lg EID50), and hemagglutinating activity (1:1024-1:2048). The strain has ts and ca phenotype: reproductive capacity at t = 39 degrees C is 1.0 lg EID50; at t = 26 degrees C, 8.5 lg EID50. A total of 16 mutations have emerged from comprehensive sequencing of the virus genome. Among them 10 mutations were located in the genes of polymerase complex and NP, with respective amino-acid substitutions. The stability of strain characteristics, such as attenuation to humans and high reproductive capacity, were confirmed by repeated sequencing of the genome after tenfold passing of the virus in chicken embryos. Reassortants of the strain A/Hong Kong/1/68/162/35 with the wild-type viruses have inherited useful features of donor virus.

[The isolation of a reassortant strain of the A/Kiev/59/79, R (H1N1) influenza virus and its genomic characteristics]. / Poluchenie reassortantnogo shtamma virusa grippa A/Kiev/59/79, R (H1N1) i kharakteristika ego genoma.

As a result of two successive recombinations of influenza A viruses: A/Leningrad/0139/76 (H3N2) with A/PR/8/34 (H1N1) strain and the resulting reassortant A/Leningrad/0139/76, R (H3N2) with a field isolate A/Kiev/59/79 (H1N1), a virus. A/Kiev/59/79, R (H1N1) was obtained. It was established by electrophoresis in polyacrylamide gel and sequencing of kDNA fragments of its genome that the genes PB2, PB1 and NP of this virus belonged to serosubtype H3N2, while genes PA, M, and NS to serosubtype H1N1 (like A/PR/8/34). The surface glycoproteins HA and NA belonged to serosubtype H1N1/like A/USSR/90/77.

[Immunogenic activity of the viral hemagglutinin and neuraminidase from live and inactivated influenza vaccines]. / Izuchenie immunogennoi aktivnosti virusnogo gemaggliutinina i neiraminidazy zhivykh i inaktivirovannykh grippoznykh vaktsin.

Paired sera from 600 persons immunized with live or inactivated influenza vaccines have been studied in the hemagglutination inhibition (HAI) and influenza virus elution inhibition (EI) tests. The possibility of using, in principle, the EI test for the evaluation of the immunogenicity of the vaccine has been shown. The time course of antibody formation has been found to correlate with both hemagglutinin and neuraminidase of influenza virus. To evaluate the immunogenicity of influenza vaccines with greater precision, taking into account not only seroconversions routinely revealed in the HAI test, but also seroconversions registered only in the EI test is recommended.

[Antineuraminidase serum antibodies in natural influenza A and immunization with influenza vaccines]. / Antineiraminidaznye syvorotochnye antitela pri estestvennom infitsirovanii grippom A i immunizatsii grippoznymi vaktsinami.

Parallel HI and virus-elution-from-erythrocytes-inhibition (a simplified method for titration of neuraminidase antibody) tests were used for examinations of 1117 blood serum specimens from 440 adults and children under study, 5250 single serum specimens from healthy subjects from birth to 65 years of age, 38 paired serum specimens from children who experienced influenza A/Texas/1/77 disease in the epidemic of 1979-1980, and 590 paired serum specimens from subjects immunized with influenza vaccines. In 7%-23% of influenza patients and immunized subjects antibody rise was observed to only one of the influenza A virus surface antigens, hemagglutinin or neuraminidase. The protective activity of antibody to influenza A virus neuraminidase was as good as that of antihemagglutinins. Both kinds of antibody interacted in protection against the disease. Antineuraminidase antibody was found to affect the decrease in severity of the infectious process in natural infection with influenza A. The formation of immunological memory in the system of synthesis of antihemagglutinins and antineuraminidase antibodies was shown to have features in common. The pattern of heterologous immune responses in immunized subjects and patients with influenza showed all antigenic varieties of neuraminidase N2 as well as neuraminidases N1 and N2 to share common cross-reacting determinants.

[Evaluation of the postvaccination level of influenza antibodies by means of the radial immunodiffusion and hemagglutination inhibition reactions]. / Otsenka postvaktsinal'nogo urovnia protivogrippoznykh antitel s pomoshch'iu reaktsii radial'noi immunodiffuzii i tormozheniia gemaggliutinatsii

Comparative data on the antibody levels obtained by the radial immunodiffusion and hemagglutination inhibition tests were studied. The possibility of using the radial immunodiffusion test for evaluation of the level of influenza antibody in human sera was confirmed. Because this method has comparatively low sensitivity (positive results were obtained only with sera having angihemagglutinin titers of 1:80 or higher), it may have only a limited use in studies of immunogenic activity of live influenza vaccines.

Comparative study of the electrophoretic mobility of the RNA of influenza parent and recombinant strains.

The electrophoretic mobility of the RNA of Influenza viruses A/WSN, A/Singapore and their antigenic recombinants X-7 and X-9 was investigated. The genome of each virus studied consisted of seven pieces of RNA. The electrophoretic profile of the influenza virus A/WSN RNA differed from that of A/Singapore but resumbled that of the recombinant X-9 genome. The essential differences were connected with the properties of the fifth fragment of the RNA. The molecular weight of this RNA species of influenza virus A/WSN and X-9 was 5.4 X 10(5) AND 5.3 X 10(5) daltons (d) respectively. The molecular weight of the corresponding component of the influenza viruses A/Sinapore and X-7 RNA was 6.2 X 10(5) and 6.3 X 10(5)d respectively.

[Electrophoretic motility of RNA of recombinant influenza virus strains X-7 and X-9]. / Elektroforeticheskaia podvizhnost' RNK rekombinantnykh shtammov virusa grippa X-7 i X-9

The electrophoretic motilitiy of RNA of recombinant influenza virus strains X-7 and X-9 differing in the antigenic structure of hemagglutinin and neuraminidase was studied. The genome of these viruses was found to be fragmentary and to consist of 7 RNA molecules. Significant differences in the electrophoretic motility of the middle-molecular RNA compounds of influenza X-7 and X-9 virus were demonstrated, particularly of the V fragment the molecular weight of which was lower in influenza X-9 virus.

The effect of species and organ-specific features of tissue systems on the reactogenic and immunogenic properties of influenza virus.

The dynamics of changes in the reactogenic and immunogenic properties of influenza A/Hong Kong/1/68 (H3N2) virus in the course of serial passages in white mice, chick embryos, chick, cow and pig embryo kidney tissue cultures and in rat, guinea pig, chick embryo, cow embryo and pig embryo trachea organ cultures was studied. The rate of virus attenuation was found to depend not only on the species origin of tissue systems but also on their organ specificity. In rapid, 24-hour passages in chick embryos attenuation of the virus developed more rapidly and its immunogenic potency was retained better than in 48-hour passages or cultivation in another tissue system.

The serological differentiation of viruses in the tick-borne encephalitis subgroup by the gel-diffusion method.

A study has been made of the suitability of several modifications of the gel-diffusion test for differentiating between the various arboviruses in the tick-borne encephalitis subgroup and for obtaining indications as to the antigenic structure of these arboviruses.It was found that use of antisera and antigens in a square or hexagonal array in the gel-diffusion test allowed differentiation of the various arboviruses: related arbovirus pairs gave continuous precipitation lines, while less closely related pairs gave spurring. These phenomena could be explained on the assumption of a common precipitinogen for all members of the tick-borne encephalitis subgroup, with immunological modifications specific to the different members of the subgroup.It was further found that various other methods tested were not suitable for the differentiation of the arboviruses in this subgroup-namely, the cross-absorption of immune sera with homologous and heterologous viruses, titration of immune sera in the presence of homologous and heterologous viruses, and determination of the density of precipitation lines.