[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.

[The mapping of the hemagglutinin sites of the influenza viruses H3N2 isolated in 1990-1993]. / Kartirovanie saitov gemaggliutinina virusov grippa H3N2 1990--1993 gg. vydeleniia.

The antigenic structure of hemagglutinin (HA) of influenza A (H3N2) viruses was found to have undergone significant changes which markedly distinguished the new isolates of previously occurring strains. Investigations of the epidemic variants using monospecific and monoclonal antibodies revealed strains with original HA sites previously unfound in H3N2 viruses. The emergence of the sites with the new properties determined the epidemic activity of the viruses isolated in this period.

[The incidence of detecting influenza virus antigens in the peripheral blood lymphocytes of donors in relation to the epidemic activity of influenza viruses A and B]. / Chastota vyiavleniia antigenov virusov grippa v limfotsitakh perifericheskoi krovi donorov v zavisimosti ot épidemicheskoi aktivnosti virusov grippa A i B.

Antigens of influenza A and B viruses in the peripheral blood lymphocytes of normal human subjects are found regularly both in epidemic and interepidemic periods. The level of detection of viral proteins in lymphocytes varies widely and correlates with the epidemic activity of the viruses. Influenza virus antigens were found several months before a rise in the incidence of the disease, the per cent ratio of the identified antigens correlating with the pattern of antigen detection in nasopharyngeal washings during an epidemic outbreak. Most frequently, the antigen found in lymphocytes was that of the main etiological agent of a definite epidemic; less frequently the hemagglutinin of the virus accompanying the one dominant in a given epidemic was found.

[The antigenic structure of influenza B viruses isolated in 1991]. / Antigennaia struktura virusov grippa B, vydelennykh v 1991 g.

A comparative immunological analysis of the antigenic structure of reference influenza B viruses of 1940-1984 and isolates of 1986-1991 using monospecific antibodies to individual antigenic determinants and monoclonal antibodies to hemagglutinin of B/Oregon/5/80 virus demonstrated a further antigenic drift of influenza B viruses from the reference variants B/Victoria/2/87 and B/Yamagata/16/88. Alongside with circulation of viruses with new antigenic properties, variants were found in the epidemic outbreak of 1991 whose hemagglutinin had common antigenic markers with those of variants of the previous years.

[The antigens and nucleotide sequences of influenza A and B viruses in the lymphocytes of human peripheral blood]. / Antigeny i nukleotidnye posledovatel'nosti virusov grippa A i B v limfotsitakh perifericheskoi krovi cheloveka.

Markers of influenza A and B viruses (antigens of hemagglutinin and specific nucleotide sequences) were detected in lymphocyte preparations from normal subjects. The rate of detection of the antigens and specificity (type and subtype appurtenance) of the markers correlated with the influenza epidemic situation. Lower titers of antibodies to the virus whose antigens were present in lymphocytes were observed.

[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.

[New sites in the hemagglutinin composition of epidemic variants of the influenza virus A (H3N2) from 1989-1990]. / Novye saity v sostave gemaggliutininov épidemicheskikh variantov virusa grippa A (H3N2) 1989--1990 gg.

Immunological analysis of the antigenic structure of hemagglutinin of newly isolated variants of influenza (H3N2) virus carried out using monoclonal and monospecific antibodies to individual antigenic sites of hemagglutinin showed the 1989-1990 isolates to be markedly different in their antigenic properties from the variants isolated in previous years. Sites with new antigenic properties were determined in hemagglutinin of the isolates. Wide variability was found in the region of three immunodominant sites. The fact of circulation in the human population of influenza viruses of one subtype with different antigenic structures within the limits of one epidemic season was established.

[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.

[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.

[An analysis of the antigenic structure of the hemagglutinins from different strains of the influenza B virus by using monoclonal antibodies]. / Analiz antigennoi struktury gemaggliutininov razlichnykh shtammov virusa B s pomoshch'iu monoklonal'nykh antitel.

A comparative immunological analysis of the antigenic composition of hemagglutinin (HA) of influenza B virus drift-variants isolated during 46 years was carried out using monoclonal antibodies (MAb) to HA of B/Oregon 5/80 virus in HI test and solid-phase enzyme immunoassay. The presence of type- and group-specific antigenic determinants was demonstrated which agreed with our previous data obtained in studies with polyvalent sera. However, using Mab three more group-specific determinants were detected which characterize HA of influenza B viruses isolated in 1970-1979, 1970-1984, and 1970-1986.

[Functional activity of glycoproteins from interepidemic isolates of the influenza virus]. / Izuchenie funktsional'noi aktivnosti glikoproteidov mezhépidemicheskikh izoliatov virusa grippa.

The results of the study into the function of glycoproteins of influenza viruses isolated in the 1987 interepidemic period. Natural isolates were found to have virus particles with deficient neuraminidase activity but retained hemolytic and infectious activity. Biological sequences of the lack of neuraminidase activity in the isolates consisted in disorders of sialic acid metabolism in the infected cells, blocking of the receptor site of hemagglutinin and increased sensitivity to inhibitors. It is assumed that the interepidemic virus isolates represent a biologically heterogeneous population in which particles with deficient neuraminidase activity are prevalent.

[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.

[The use of immunoenzyme analysis in studying the etiologic structure of influenza morbidity in 1985-1988]. / Primenenie immunofermentnogo analiza dlia izucheniia étiologicheskoi struktury zabolevaemosti grippom v 1985--1988 gg.

In the periods of epidemic increases in the incidence of influenza in 1985-1988, approximately 600 patients with clinical diagnoses of ARVI and influenza were examined for the presence of viral antigen in nasopharyngeal washings by solid-phase enzyme-immunoassay and for antibody rises in paired blood sera. The use of modified SPEIA and original test sera for influenza type A and B viruses in rapid diagnosis of influenza made it possible to decode the etiology of the epidemic situations in 1985-1988. Influenza A and B virus antigens were detected in a high portion of the examined nasopharyngeal washings. The analysis of the distribution of positive results in the detection of viral antigen in the clinical specimens and in influenza serodiagnosis demonstrated a high correlation of the results (93.9%). The etiological pattern of influenza in recent years is characterized by simultaneous circulation in the human population of influenza A (H1N1, H3N2) and B viruses, as reflected by detection of mixed infections in 1-3% of the cases.

[Antigenic specificity of neuraminidase and structure of neuraminidase gene of influenza A(H1N1) serotype Hsw1N1 viruses isolated from man and animals]. / Antigennaia spetsifichnost' neiraminidazy i struktura genov neiraminidazy virusov grippa A(H1N1)-serovariant Hsw1N1, vydelennykh ot cheloveka i zhivotnykh.

The enzyme immunoassay and neuraminidase activity inhibition test using polyclonal and monospecific antineuraminidase sera were employed to establish the similarities and differences in the antigenic structure of neuraminidase of influenza A viruses (H1N1), serovariant Hsw1N1, isolated from man in Alma-Ata (USSR), 1984, New Jersey (USA), 1976, and Pazardjik (BPR), 1982, as well as from swine and birds. Oligonucleotide mapping revealed significant structural differences in the genes coding for neuraminidase of Hsw1N1 viruses. The experimental results indicate a high degree of the enzyme variability in this group of viruses.

[Antigenic structure of hemagglutinins of influenza H1N1 (Hsw1N1) virus isolated from humans and ducks]. / Antigennaia struktura gemaggliutininov virusov grippa H1N1 (Hsw1N1), vydelennykh ot liudei i utok.

The method of specific adsorption followed by the use of antisera in HI test and competitive enzyme immunoassay was used to study the antigenic composition of hemagglutinins (HA) Hsw1 in influenza viruses isolated in 1982 from humans in Bulgaria and in 1976 in Canada from ducks as well as their antigenic relationships with HA of Hsw1 variant isolated from swine and man. Hemagglutinins of Hsw1 strains isolated from man in Bulgaria and Alma-Ata were found to be similar to HA of A/New Jersey/8/76 virus in two determinants and with hemagglutinin of the classic virus of swine in three determinants. The HA of A/duck/Alberta/35/76 virus was similar in three determinants to HA of A/New Jersey/8/76 virus and in two determinants with other Hsw1 variants. The similarities and differences in antigenic determinants of HA in Hsw1 viruses isolated from man and animals attest to their common origin and different modes of variability.

[Antigenic-genetic connections between human and animal influenza viruses]. / Antigenno-geneticheskie sviazi virusov grippa cheloveka i zhivotnykh.

A comparative immunological analysis of the composition of antigenic determinants (AGD) in hemagglutinins of human influenza A virus (HIAV) of the serosubtypes H1, H2, H3, and in hemagglutinins of animal influenza viruses (AIV) of the serosubtypes H1, H3-H6, H8-H11 with 25 polyclonal highly active sera was demonstrated. Using original monospecific mon AGD in HIAV and AIV hemagglutinins was demonstrated. Using original monospecific antibodies to individual AGD, those AGD contributing to similarity and differences between HIAV and AIV were determined. It was found that influenza A. virus strains isolated from man in the USSR in 1986 were identical in the antigenic structure of hemagglutinin with that isolated from a tern in 1973 (A/tern/Turkmenistan/18/73).

[The use of colloidal gold-labelled antibodies for demonstrating viral antigens]. / Primenenie mechennykh kolloidnym zolotom antitel dlia indikatsii virusnykh antigenov.

The principal possibility of using antibodies conjugated with colloid gold for better visualization of viruses, viral antigens, and their immune complexes in electron microscope was studied on the experimental model of HBs-antigen and Venezuelan equine encephalomyelitis virus. The same method was used for the study of the thin structure of influenza A (H1N1) virus hemagglutinins using monoreceptor antisera.