[Characteristics of the antigenic composition of influenza A (H3N2) virus hemagglutinins isolated 1979-1080]. / Osobennosti antigennogo sostava gemaggliutininov virusov grippa A (H3N2) 1979-1980 gg. vydeleniia.

The results of comparative immunological analysis of epidemic influenza virus strains of 1979-1980 indicate an emergence in the antigenic composition of virus hemagglutinins of two qualitatively new antigenic determinants differing from those of previously investigated influenza H0N1, H1N1, H2N2, H3N2 viruses. It is suggested that the viruses of recent years having completely lost the relationship with the ancestor of the H3N2 subtype and having very little similarity with viruses occuring in 1975-1978 are precursors of the emergence of a new antigenic variant.

[Determination of the antigenic composition of the hemagglutinins of influenza viruses H1N1]. / Opredelenie antigennogo sostava gemaggliutninov virusov grippa H1N1.

A comparative immunological analysis of the antigenic composition of hemagglutinins (HA) of influenza A viruses isolated from man and animals was done by the method of specific adsorption of immunoglobulin fractions recovered from sera of rabbits and rats immunized with influenza H1N1 viruses isolated in 1930-1948. A single determinant which remains antigenically stable from 1930 up to the present time was found in HA of human influenza H1N1 viruses (1933-1957, 1977-1981), swine virus A/Swine/Iowa/30, and whale virus A/whale/Pacific Ocean/8/76. Animal influenza viruses A/swine/Iowa/30 and A/whale/Pacific Ocean/8/76 have in their HA one more determinant contributing to the similarity of the swine virus with human A/PR8/34 virus, and the whale virus with human A/W.Smith/33 virus.

[The detection of the antigens of influenza viruses A and B in the blood of healthy donors]. / Obnaruzhenie antigenov virusov grippa A i B v krovi zdorovykh donorov.

Blood clots and sera were obtained from donors at a Moscow city transfusion clinic during 1984-1988 and tested by indirect solid-phase enzyme immunoassay with original test-sera to hemagglutinating antigens of influenza A (H1 and H3) and B viruses. Examinations of 1714 blood samples demonstrated hemagglutinating antigens of different specificity (from 0.8% to 35%), the detection rate of one or another antigen correlating with the epidemic activity of influenza virus serovariants A and B. The virus-specific antigens, however, were almost regularly detected in the blood of healthy subjects in the interepidemic seasons as well. The highest number of positive results was observed in tests with blood clot or serum. The results indicate the principal capacity of influenza virus to persist in apparently normal subjects.

[A comparative study of monoclonal and monospecific antibodies in determining the immunodominant antigenic sites of influenza virus A (H3N2) hemagglutinin]. / Sravnitel'noe issledovanie monoklonal'nykh i monospetsificheskikh antitel v opredelenii immunodominantnykh antigennykh saitov gemaggliutinina virusa grippa A (H3N2).

Comparative studies of monospecific (MSA) and monoclonal (MCA) antibodies showed MSA to detect three non-overlapping immunodominant sites on the surface of hemagglutinin (HA) molecule whereas MCA established more subtle differences in HA antigenic structure on the level of epitopes with different immunological significance. The activity of MSA and MCA differed in various tests. While MCA were more active in HI and EIA tests, MSA had a higher neutralizing activity, reducing the infectious virus titre by 5.0-7.5 Ig. Similar reduction of the virus biologic activity was observed only with two MCA whereas the other 20 MCA had a poor neutralizing effect (the virus titre reduction not more than by 2.5 Ig). The employment of MSA and MCA gives most complete information on antigenic restructuring of influenza virus HA at the site level and more subtle structures, epitopes, in the process of evolutionary variability.

[The characteristics of the evolutionary variability of influenza A (H1N1) viruses]. / Osobennosti évoliutsionnoi izmenchivosti virusov grippa A (H1N1).

Studies of the antigenic structure of hemagglutinins of influenza A (H1N1) viruses isolated in 1978-1988 using monospecific and monoclonal antibodies demonstrated the strains of the H1N1 subtype to be highly apt to antigenic drift. The evolutional variability of that period was peculiar and characterized by antigenic drift in various directions. In those years, the variants were regularly isolated which had retained the determinants of viruses of 1933-1957 circulation period in their hemagglutinin structure. The variants containing in their hemagglutinin 2 antigenic sites common with A/USSR/090/77 virus and antigenic groupings characterizing the strain specificity of each isolate, were epidemically active. At the same time, epidemically important variants were dominant whose properties were markedly different from those of previously known viruses. Their hemagglutinin contained 2 basically new antigenic determinants. This direction of evolutional development of influenza A (H1N1) virus is the most prospective epidemically.

[Effect of antilymphocyte serum on the course of influenzal infection in mice]. / Vliianie antilimfotsitarnoi syvorotki na techenie grippoznoi infektsii u myshei.

The effect of antilymphocyte serum (ALS) on the course of infection produced by influenza A/PR8/34 virus in mice weighing 10-12 g was studied. Inoculation of mice with ALS produced a longer persistence of influenza virus in the lung tissue and in the blood (up to 15 days of the observation period), whereas in the controls no influenza virus could be isolated after 9 days. No antibody production in ALS-treated mice was observed. The immunosuppression in mice reduced the extent of involvement of the lungs and lethality as compared with the control animals, being conducive to the change of the acute influenza infection into chronic one.

[Isolation of strain-specific and cross-reacting antibodies to influenza virus hemagglutinins from heterogenous populations of hyperimmune influenza sera]. / Vydelenie shtammospetsificheskikh i perekrestno reagiruiushchikh antitel k gemaggliutininam virusov grippa iz geterogennykh populiatsii protivogrippoznykh giperimmunnykh syvorotok.

A population of monoreceptor cross-reacting antibodies to a common antigenic determinant H1.1 present on the surface of hemagglutinin molecules of H0, H1 and Hsw1 subtypes has been isolated from a heterogenous population of antihemagglutinating antibodies of influenza hyperimmune sera. Selective adsorption yields highly active strain-specific sera to HA of A/FM/1/47 and A/Netherlands/36/56 viruses. Populations of strain-specific antibodies to HA of A/Moscow/Pan/52 and A/USSR/090/77 viruses were found to be identical, attesting to the complete similarity of the antigenic composition of HA of these viruses. The hyperimmune serum of A/Brazil/11/78 virus was found to contain a population of strain-specific antibodies different from HA of other H1N1 viruses studied. This shows that drift variants of A/USSR/090/77 virus appeared in 1978.

[Functional activity of monoclonal and monospecific antibodies in the interaction with antigenic sites of influenza virus hemagglutinin]. / Funktsional'naia aktivnost' monoklonal'nykh i monospetsificheskikh antitel pri vzaimodeistvii s antigennymi saitami gemaggliutinina virusa grippa.

Monospecific antibodies to three nonoverlapping sites of influenza A/Singapore/1/57 (H2N2) virus isolated from hyperimmune serum by specific adsorption were characterized by capacity to inhibit virus hemagglutination, immunochemically interact with hemagglutinin, and neutralize the virus (6-7.5 lg). Monoclonal antibodies to the same virus hemagglutinin displayed an even higher activity than monospecific antibodies in serological and immunochemical tests and were characterized by a rather low (1.0-4.5 lg) or null activity in biological neutralization of the virus.

[Hemagglutinin antigens of influenza viruses isolated from man and birds]. / Antigeny gemaggliutininov virusov grippa, vydelennykh ot cheloveka i ptits.

Immunological analysis has shown hemagglutinins of avian viruses like hemagglutinins of human viruses to have a complex antigenic composition. Three antigenic determinants were discovered in hemagglutinin of A/Chicken/12/71 virus previously designated H3 and in hemagglutinin of A/Tern/18/73 virus previously designated Hav7. The H3 determinant and the second determinant are identical in avian and A/Hong Kong/1/68 human viruses. In addition, hemagglutinins of avian viruses have a determinant specific for each virus which is lacking in human influenza virus hemagglutinin.

[Immunological study of antigenic determinants in the isolated hemagglutinin of the influenza A virus (H1N1)]. / Immunologicheskoe izuchenie antigennykh determinant v izolirovannom gemaggliutinine virusa grippa A (H1N1).

A preparation of isolated subunits of influenza A (H1N1) virus hemagglutinin was examined for antigenic properties by four serological tests: radioimmunoassay, radial immunodiffusion test, complement fixation test, and hemagglutination inhibition test with hyperimmune polyclonal serum to intact virion as well as with monospecific antibodies to individual antigenic determinants obtained by adsorption technique. In isolated hemagglutinin subunits, radioimmunoassay identified three main virus-specific antigenic sites identical to antigenic determinants in the hemagglutinin of the intact virion. No neuraminidase was found in the hemagglutinin preparation but increased serological activity of host cell antigens was observed.

[New strain-specific determinants in the hemagglutinins of influenza B viruses isolated in 1983-1984]. / Novye shtammospetsificheskie determinanty v gemaggliutininakh virusov grippa B, izolirovannykh v 1983-1984 gg.

A comparative study of sensitivity to inhibitors and antigenic composition of hemagglutinins of influenza B virus strains isolated in the epidemic season of 1983-1984 and those circulating in 1940-1981 was carried out. The method of selective adsorption of highly active rabbit and rat sera demonstrated that hemagglutinins of contemporary influenza B viruses had both common cross-reacting determinants with previously circulating variants and qualitatively different, strain-specific ones. Among the variants isolated in 1983-1984, three subgroups of viruses were detected with different strain-specific hemagglutinin determinants.

[Immunobiological analysis of isolated subunits of influenza virus hemagglutinin]. / Immunobiologicheskii analiz izolirovannykh sub''edinits gemaggliutinina virusa grippa.

The immunogenic properties of isolated subunits of influenza A/FM/1/47 (H1N1) virus hemagglutinin were studied. The antihemagglutinating serum was tested by the CFT, HI, competitive solid-phase radioimmunoassay, and biological neutralization test. The antiserum was found to contain populations of antibodies to the three main antigenic determinants of hemagglutinin identical to the determinants of the intact virion, as well as antibodies to the antigenic components of host cells. The antiserum to hemagglutinin as well as monospecific antibodies to individual antigenic determinants of hemagglutinin exhibited a high virus-neutralizing activity for the homologous virus.

[The antigenic characteristics of the influenza virus subpopulations isolated from a single patient]. / Antigennaia kharakteristika subpopuliatsii virusa grippa, izolirovannykh ot odnogo bol'nogo.

Examinations by HI and EIA of influenza A (H3N2) virus isolates of 1985-1990 showed the strains derived from nasopharyngeal washings from patients to present very frequently as phenotypic mixtures of stable virus variants. Immunological analysis with monospecific antibody to hemagglutinin antigenic sites revealed a wide spectrum of antigenic activity based on the degree of relationship with viruses of previous years. By means of the immune pressing with antibody of different specificity the isolated strains could be divided into 2 subpopulations each characterized by the presence of only three antigenic sites. The subpopulations homogeneous by the antigenic composition of hemagglutinin represented the strains with antigenic markers of hemagglutinins of previous variants with drift variants of epidemic nature.

[Detection of a heterogeneous population of influenza virus type A/H1N1 with monoreceptor sera to hemagglutinin antigenic determinants]. / Vyiavlenie geterogennosti populiatsii virusa grippa tipa A/H1N1 monoretseptornymi syvorotkami k antigennym determinantan gemaggliutinina.

Studies of the antigenic composition of hemagglutinins of influenza H1N1 virus variants isolated in 1981 using monoreceptor antibody to individual antigenic determinants obtained by the selective adsorption method showed some variants to represent heterogeneous populations manifesting antigenic properties of different H1N1 viruses. Passages of the heterogeneous virus in the presence of antiinfluenza serum resulted in cloning a subpopulation with the antigenic properties of the hemagglutinin similar to that of H1N1 viruses which had circulated in the end of the first period of epidemic activity of H1N1 viruses. The method "from-plaque-to-plaque" passages in MDCK cells yielded from the heterogeneous population a homogeneous variant which by the hemagglutinin antigenic properties was similar to H1N1 viruses isolated in 1956-1957.

[Monoreceptor sera to the antigenic determinants of influenza virus A hemagglutinin]. / Monoretseptornye syvorotki antigennym determinantam gemaggliutinina virusa grippa A.

The method of specific adsorption was used to produce monoreceptor sera to individual antigenic determinants of hemagglutinin of influenza A virus, Hong Kong variant. The sera were completely free of inhibitors, contained no antibody to neuraminidase or host cell antigens. The monoreceptor sera were used in HI tests and immunoelectrophoresis for the qualitative and quantitative analysis of the antigenic variants isolated in 1968--1977. It was shown that alongside with the appearance of qualitatively new antigenic determinants changes in the content of some or other antigens in influenza virus hemagglutinins occurred.

[Interaction of immune and normal macrophages with the influenza virus]. / Vzaimodeistvie immunnykh i normal'nykh makrofagov s virusom grippa.

The interaction of macrophage cultures from immune and non-immune animals with influenza A/PR8/34 virus was studied. Significant differences were demonstrated between immune and normal macrophages. Influenza virus could be found in immune macrophages for a considerably shorter period than in normal macrophages. In immune macrophage cultures as compared with normal macrophages the synthesis of V- and S-antigens occurred only in a small number of cells. The study of the hemadsorbing capacity of macrophages showed the number of cells adsorbing erythrocytes to increase in normal macrophage cultures in contrast to those of immune macrophages. When macrophage cultures were inoculated with influenza virus, it exerted a cytopathic effect on normal macrophages at a lower multiplicity of infection whereas much greater infectious doses were required to produce the CPE in immune macrophages. The experimental results suggest that in infection or immunization certain changes occur in macrophages which may play a role in elimination of influenza virus from the body and in immune response.

[Antigenic markers in the hemagglutinins of influenza type A viruses (H1N1) from various periods of circulation]. / Antigennye markery v gemaggliutininakh virusov grippa tipa A (H1N1) razlichnykh periodov tsirkuliatsii.

Hyperimmune rabbit sera were examined by specific adsorption tests for influenza viruses H1N1 isolated in 1942-1952. A comparative immunological analysis revealed the presence of three antigenic determinants in hemagglutinins (HA) of A/Bel/42, A/Weiss/43, A/FM/1/47 and A/FLW/52 viruses. Adsorption of antisera with different drift-variants of H1N1 produced monoreceptor sera to individual antigenic determinants of HA by means of which marker antigens can be identified in HA of viruses isolated in different periods, and one may have an idea of evolutionary variability of influenza virus.

[Identification of the hemagglutinating antigens of the influenza virus by immunoenzyme analysis]. / Identifikatsiia gemaggliutiniruiushchikh antigenov virusa grippa metodom immunofermentnogo analiza.

Highly active test sera detecting the presence of virus antigen both in concentrated and purified preparations and in allantoic virus cultures directly adsorbed on the solid phase have been proposed for successful identification and detection of influenza A and B virus variants. After direct sorption of purified and concentrated virus preparations, the test sera to influenza A (H1N1, H2N2, H3N2) virus detect the virus antigen in a concentration of 8 ng/ml, test sera to influenza B virus in a concentration of 40 ng/ml. After sorption on the solid phase of allantoic virus cultures the test sera detected influenza A virus antigen in a dose of 0.25-1 agglutinating units (AU), and antigen of influenza B virus in a dose of 1-2 AU.

[Role of phagocytes and antibodies in freeing the body from influenza virus]. / Rol' fagotsitov i antitel v osvobozhdenii organizma ot virusa grippa

Persistence of influenza virus in normal and immune mice was studied by determinations of the virus infectivity and by the immunofluorescence procedures. After intraperitoneal inoculation the virus could be found in macrophages of the peritoneal exudate in both normal and immune animals. However, in macrophages of normal mice synthesis of V- and S-antigens of influenza virus occurred indicating the possibility of virus reproduction in them, whereas in macrophages of immune animals there was practically no synthesis of S-antigen despite a greater number of cells with V-antigen of influenza virus in their cytoplasma. The assumption that elimination of influenza virus from the body is due to specific antibody and immunologically changed macrophage elements is substantiated.

[Speed and intensity of the immune response to the administration of inactivated influenza vaccine in relation to neuraminidase activity]. / Bystrota i intensivnost' immunnogo otveta na vvedenie inaktivirovannoi protivogrippoznoi vaktsiny v zavisimosti ot aktivnosti neiraminidazy

A comparative study of the rate of appearance of specific virus antigen in immune competent organs of mice immunized with inactivated influenza vaccine with active neuraminidase or a vaccine devoid of the neuraminidase activity was carried out by means of the immunofluorescence test and the serological tests. A considerable delay in the time (by 16--18 hours) of detection of virus antigen in cells of lymph nodes of mice as well as later (1--2 days) and less intensive (2--4-fold) production of specific virus antibody was demonstrated after immunization of mice with the vaccine without the active enzyme.