[Evaluation of the immunological activity and safety of group B meningococcal vaccine prepared from a natural complex of specific polysaccharide and outer membrane proteins]. / Otsenka immunologicheskoi aktivnosti i bezopasnosti meningokokkovoi gruppy B vaktsiny iz prirodnogo kompleksa spetsificheskogo polisakharida i belkov naruzhnoi membrany.

Immunological activity and safety of group B meningococcal vaccine prepared from a natural complex of specific polysaccharide and outer membrane proteins were under study. The immunological safety of the vaccine was evaluated by the absence of antibodies to denaturated and native DNA (d-DNA and n-DNA). As shown with the use of the enzyme immunoassay (EIA), the administration of the vaccine did not induce antibody formation to d-DNA and n-DNA during the observation period. The titer of bactericidal antibodies in the immune bacteriolysis assay (IBA) to the vaccine strain B:2b:P1.2 after immunization increased four-fold and greater in 80% of the vaccinated persons. The significant increase of bactericidal antibodies to heterologous strains B:2a:P1.2 and B:15:P1.7 was registered in 20-30% of the vaccinees, respectively. A month after the repeated vaccination an increase in specific IgG antibodies to the complex antigen was found to occur according to EIA results. The use of RIB made it possible to evaluate the preventive activity of group B meningococcal vaccine as a whole and to suppose that the vaccine induced mainly type-specific response.

[The isotypic characteristics of antibodies in persons inoculated with a serogroup-A meningococcal polysaccharide vaccine]. / Izotipicheskaia kharakteristika antitel u privitykh meningokokkovoi polisakharidnoi vaktsinoi serogruppy A.

In this work the results of the study of specific antibodies (Ab), isotypes IgM, IgG, IgA, types kappa and lambda, in 235 serum samples from 27 adults immunized with group A meningococcal polysaccharide vaccine (AMPV) in a single injection of 50 microg and from 20 control subjects are presented. The study was made by the method of sandwich EIA. The study revealed that in a month after the injection of the vaccine the intensive synthesis of IgA, IgG and IgA Ab and their subsequent circulation for 2 years were observed; 3 years after immunization (the term of observation) the prevalence of IgG and IgA antibodies was registered. Prior to immunization the ratio of kappa and lambda Ab was 1.7. In a month after immunization the maximum ratio of 3.2 was achieved and in all subsequent terms of examination this ratio remained higher than prior to immunization (3.1 -- 2.3). As revealed in this study, the injection of AMPV induced the intensive synthesis of antibodies of types kappa and lambda during the first year after immunization, then the production of type lambda Ab decreased by the second year and in 2 and 3 years after immunization the circulation of type kappa Ab prevailed.

[The ultrastructural characteristics of Neisseria meningitidis strains isolated in different forms of infection]. / Osobennosti ul'trastruktury shtammov Neisseria meningitidis, vydelennykh pri razlichnykh formakh infektsii.

The electron microscopic study of cell populations of the first generation of several N.meningitidis strains, isolated from humans and grown on artificial culture medium (Hottinger's serum agar) has made it possible to establish that these organisms are morphologically heterogeneous. It was manifested by the presence of 7 morphological variants of cells in their cultures (different strains have different proportions of these variants): (a) "normal" and similar to normal diplococcal variants; (b) atypically dividing cells; (c) spheroplastic forms; (d) protoplastic forms (typical and atypical); (e) variably gemmating forms; (f) microforms and (g) gigantic forms. These data are of interest for the microbiological diagnosis of meningitis.

[The Neisseria meningitidis serotypes and subtypes circulating among bacterial carriers in Moscow (1989-1991)]. / Serotipy i subtipy Neisseria meningitidis, tsirkuliruiushchikh sredi bakterionositelei v Moskve (1989--1991 gg.).

N. meningitidis strains isolated from 218 healthy carriers in 1989-1991 in closed communities of adults, irrespective of cases of meningococcal infection registered in these communities, were characterized with a variety of different type and subtype antigens. Only in 139 strains (63.76%) their types and/or subtypes could be determined with the use of a set of 6 serotypes and 11 subtypes of monoclonal antibodies. 26 group B strains and 31 group C strains had multiple antigenic composition. 13 group A strains were found to be more homogeneous: 8 of them, isolated in one area, belonged, according to Dr. Achtman's data, to a definite clone VI-1, heretofore unknown. No prevailing serotype/subtype could be revealed, which reflected the wide heterogeneity of N. meningitidis at the period of the decrease of morbidity in meningococcal infection. The observed stability of serotype/subtype of strains, isolated from the same carriers and circulating in the same communities, suggests that the serotype/subtype of N. meningitidis is a valuable epidemiological marker.

[The antilysozyme activity of the meningococci isolated from bacterial carriers in closed collectives with different epidemiological situations]. / Antilizotsimnaia aktivnost' meningokokkov, vydelennykh u bakterionositelei v zakrytykh kollektivakh s razlichnoi épidemiologicheskoi obstanovkoi.

The degree of the antilysozyme activity (ALA) of 430 Neisseria meningitidis strains isolated from 379 healthy carriers in 11 closed groups with different epidemiological situation and in 3 family foci was studied by the method of delayed antagonism. 87% of the strains exhibited ALA in a concentration of lysozyme between 1 and 10 micrograms per ml of the medium; about 11% of them were highly active, inactivating 20 and 25 micrograms of lysozyme per ml. ALA was shown to be the constant sign of carriership. The ALA of 39 strains isolated in cases of prolonged carriership (exceeding 2 weeks) was essentially higher than the ALA of 20 strains obtained in a single isolation. N. meningitidis strains of groups A, B and C, mostly responsible for the appearance of the generalized forms of diseases, were essentially less active than N. meningitidis strains of groups X, Y, Z, 29E, W-135, as well as strains not classified with any group. No correlation between ALA and the presence or absence of hyaluronidase was noted. Analysis of the data obtained in this study revealed that the ALA of N. meningitidis strains isolated in closed groups and families was not linked with the presence or absence of morbidity in the generalized forms of meningococcal infection and the spread of carriership in these groups, but reflected only differences in the serological picture of strains circulating there. The role of ALA in the formation of prolonged N. meningitidis carriership requires further study.

[Safety, reactogenicity and immunological activity of a group A meningococcal polysaccharide vaccine for children 1-4 years old]. / Bezvrednost', reaktogennost' i immunologicheskaia aktivnost' meningokokkovoi polisakharidnoi vaktsiny gruppy A dlia detei 1--4 let.

In the controlled trial carried out among children aged 1-4 years, the safety, reactogenicity and immunological potency of group A meningococcal polysaccharide vaccine produced at the Gabrichevskii Research Institute of Epidemiology and Microbiology (Moscow) were studied. The vaccine under test was introduced in two doses containing 15 and 25 micrograms of meningococcal polysaccharide. Both doses were shown to be safe, faintly reactogenic and immunologically potent. Systemic reactions were manifested by a transient rise in temperature to subfebrile levels in 19% and to 37.8-38.2 degrees C in 4.7% of the vaccinees. The temperature dropped to the normal level by the end of the first day following vaccination. At the site of injection skin hyperemia up to 2-3 cm in diameter was registered in 74% and up to 5-6 cm in diameter, in 6% of the vaccinees. Hyperemia disappeared on day 2 after vaccination. The production of antibodies to group A meningococcal polysaccharide occurred in response to both doses under test, and the elevated antibody level (in comparison to the initial one) was retained perceptibly longer in response to a dose of 25 micrograms; this dose, considering its low reactogenicity, was chosen as the optimal dose for children of the above age group.

[Diagnostic test system for detecting the meningococcal antigen by erythro-immunoadsorption]. / Diagnosticheskaia test-sistema dlia vyiavleniia meningokokkovogo antigena metodom éritroimmunoadsorbtsii.

The authors have developed a test-system for detection of group A meningococcal polysaccharide, based on the sandwich erythro-immunoadsorption ultra-microtechnique with the use of the Terasaki plates as a solid-phase carrier. The system, equivalent to ELISA in its high sensitivity and specificity, is more rapid and less expensive, permitting the detection of 1 mg/ml of the antigen in 20 microliter of the tested liquid within an hour. The results of the study of CSF samples from 28 patients with meningococcal infection were in good correlation with the ELISA results. The new test-system is recommended for practical use as a routine technique for the specific diagnosis of meningococcal meningitis and for the control of the effectiveness of the treatment.

[Comparative evaluation of different meningococcal group-specific erythrocyte diagnostic kits in passive hemagglutination test]. / Sravnitel'noe izuchenie razlichnykh meningokokkovykh gruppospetsificheskikh éritrotsitarnykh diagnostikumov v reaktsii passivnoi gemaggluitinatsii.

The comparative evaluation of the sensitivity and specificity of serogroup A, C, Y meningococcal antigenic preparations obtained by different methods was carried out by means of the passive hemagglutination test. In case of group 0 (I) human red blood cells sensitized with serogroup A and C vaccinal preparations obtained by Gotschlich's method (designated as A-1 and C-1) were used. In the other case formalin-treated sheep red blood cells sensitized with group-specific polysaccharides obtained by alcohol precipitation from the cultural fluid of group A, C and Y meningococci with subsequent heating (designated as A-2, C-2, Y) were used. Titrations with commercial immune rabbit sera showed that both variants of the antigenic preparations were similar in their specificity and sensitivity. In patients with the symptoms of meningitis the diagnostic titer was 1:40 for preparations A-1, C-1 and 1:80 for preparations A-2, C-2 and Y. The results of the examination of 164 patients (220 serum specimens) demonstrated that these preparations were of equal diagnostic value.

[Various aspects of humoral immunity in meningococcal infections. II. Formation of antibodies to group A meningococci in adults with generalized meningococcal infections]. / Nekotorye aspekty gumoral'nogo immuniteta pri meningokokkovoi infektsii. Soobshchenie II. Formirovanie antitel k meningokokku gruppy A u vzroslykh bol'nykh generalizovannoi meningokokkovoi infektsiei.

Altogether 258 serum samples obtained from 102 patients with generalized meningococcal infection were studied by means of the immune bacteriolysis test and the indirect hemagglutination test. This study revealed a pronounced increase in the titer of bactericidal and hemagglutinating antibodies to group A meningococcus in the process of the disease. The dynamics and intensity of antibody formation, revealed by means of the two tests, were found to be in complete correspondence. Antibody formation was most intensive in meningitis accompanied by meningococcemia. In most cases these antibodies were found to belong to the class of IgM on account of their physico-chemical nature. The highest bactericidal activity was found in the sera with high hemagglutinin titers; the summary titers of these sera were 4-64 times higher than the titers of cystein-resistant antibodies.

[Dynamics of humoral immunity indices in patients with the generalized form of meningococcal infection]. / Dinamika pokazatelei gumoral'nogo immuniteta u bol'nykh s generalizovannoi formoi meningokokkovoi infektsii.

A possibility of using the passive hemagglutination test with meningococcus diagnostic agents of groups A and C for observing the changes in the infectious process was demonstrated. Sera of patients with generalized form of meningococcus infection showed an increase (by the 2nd--3rd week) and a rapid reduction (by the 4th week) of the specific antibodies titres to the levels seen during the first days of the disease. At the remote periods after the disease--in 2 to 5 years--hemagglutinins were revealed in the same titres as in healthy persons (1:10--1:13). Study of physico-chemical nature of antibodies demonstrated that at the early stages of meningococcus infection there formed antibodies referred chiefly to macroglobulins, and at the remote periods (after 3 months)--to microglobulins.

[Humoral immunity aspects of meningococcal infection. I. A method of performing and the characteristics of the immune bacteriolysis reaction]. / Nekotorye aspekty gumoral'nogo immuniteta pri meningokokkovoi infektsii. Soobshchenie I. Metodika postanovki i osobennosti reaktsii immunogo bakterioliza.

Immune bacteriolysis test with meningococcus, group A, was used for the purpose of serum antibody study. Meningococcus cultures with a bright orange fluorescence of the colonies in oblique illumination (the I type) proved to possess the greatest lysability. Guinea pig serum sorbed with meningococcus suspension was found to be the best source of the complement. Sera obtained after 1 to 3 days of rabbit immunization, containing mostly IgM antibodies, had the greatest bactericidal capacity. Only those fractions which contained IgM possessed bactericidal activity in the hyperimmune rabbit sera with a high IgG antibody concentration. No lytic activity was displayed against meningococcus by unfractionated hyperimmune sera.

Serum immunoglobulin levels in various forms of meningococcal infection and in meningococcus carriers.

The levels of serum IgG, IgA and IgM were examined in 191 adults including 103 patients with various forms of meningococcal infection, 32 meningitis convalescents and 56 carriers, in order to elucidate the causes of different susceptibility to the meningococcal infection. The IgD level was determined in 54 meningitis patients as well as in convalescents and carriers. The amount of immunoglobulins was determined by radial immunodiffusion. The level of IgG at the beginning of the disease in patients with the generalized forms of meningococcal infection (meningitis, meningitis combined with meningococcaemia, meningococcaemia) was found to be considerably lower than in healthy subjects. The levels of all immunoglobulins, particularly of IgA and IgM, increased in the course of the disease. The levels of IgG, IgA and IgM in meningitis convalescents a year after recovery were found to be the same as in the controls. The levels of IgG, IgA and IgM in patients with meningococcal nasopharyngitis were significantly lower than in healthy subjects. The carriers showed a decreasd level of IgA and a considerably increased level of IgG while the levels of IgM and IgD did not differ from the control.