Specificity of antibodies to diphtheria toxin subunits in children with various forms of diphtheria infections

In order to study the specificity of serum antibodies to separate subunits of diphtheria toxin, SDS-electrophoresis of diphtheria toxin preliminary disintegrated on the subunits via trypsin treatment was performed, followed by immunoblotting assay. 86 blood serum samples of children with diphtheria carriers of toxigenic and non-toxigenic strains of Corynebacterium diphtheriae as well as children with other infectious diseases similar to diphtheria in their clinical manifestation, and healthy ones immunized with DTP-vaccine were tested. A special computer program was written and applied for results processing and assumption. The data obtained showed that there were particular differences in frequency of predominating the antibodies to one or another subunit of diphtheria toxin among various groups of the children. We consider that the different specificity of antibodies of sick children and children-carriers is capable to predetermine the different course of infectious process.     

Postvaccinal antidiphtheria and antitetanus immunity in patients with systemic connective tissue diseases

The retrospective evaluation of the intensity of postvaccinal immunity at different periods after the primary course of immunization against diphtheria and tetanus was made. In the sera taken from 130 children with systemic connective tissue diseases the content of antibodies to diphtheria and tetanus was determined. As revealed in this study, the protective levels of antibodies to diphtheria and tetanus toxoids were retained by both sick and healthy children for 5 years and longer. Significantly lower titers of antibodies to diphtheria and tetanus toxoids were registered in children undergoing therapy with glucocorticosteroids and cytostatics at the time of the study.     

Antidiphtheria immunity in children after immunization with adsorbed DPT vaccine and ADPT-M toxoid

Antidiphtheria immunity in children aged 3-15 years was evaluated, depending on their age, the vaccinal preparation chosen for immunization and the immunization schedule. Adsorbed DPT vaccine was shown to have a higher immunological activity in comparison with adsorbed DT toxoid with reduced antigen content. The relationship between the tension of antidiphtheria antitoxic immunity in children and the possibility of the formation of the clinical forms of diphtheria with different severity in the patients was established. Children aged 4-6 years were considered to be a group of high risk in diphtheria morbidity, as it was among the children of this group that toxic and subtoxic forms of diphtheria were most often registered (44.9 +/- 7.1% of the examinees); in addition, a high proportion of children seronegative to this infection (26,3 +/- 2.2%) was observed in this group.     

Evaluation of the immunological effectiveness of the planned vaccinal prophylaxis of diphtheria and tetanus in Sverdlovsk and Sverdlovsk Province

The level and intensity of antitoxic immunity to diphtheria and tetanus in children and adolescents were determined. The presence of tetanus antitoxin in titers exceeding the protective level in 96.3-98.5% of the examined children and adolescents is indicative of a high actual coverage by immunization. Protective titers against diphtheria were lower. There was no essential difference in the levels of protection in children immunized according to the vaccination schedule and in those immunized with some deviations from this schedule. A considerable part of newborns and children aged 3 months had antibodies to diphtheria and tetanus antitoxins. After the third booster immunization changes in antidiphtheria immunity characteristics occurred only in 2.5% of the vaccines and no changes in antitetanus immunity characteristics were observed.     

Evaluation of the reactogenicity and immunogenic potency of combined vaccine "Bubo-Kok" in the immunization of children against diphtheria, tetanus, pertussis and viral hepatitis B

Combined vaccine "Bubo-Kok" is characterized by safety and high immunological activity. The number of postvaccinal reactions in children aged 1 and 2 years, immunized with vaccine "Bubo-Kok", was not statistically different from those in groups of children immunized with adsorbed DPT vaccine, as well with such vaccine in combination with vaccine against hepatitis B. After the completion of the primary course of immunization 100% of children had protective antibody titers against diphtheria, tetanus and hepatitis B. Antibody titers against pertussis, equal to or exceeding protective titers, were found in more than 70% of immunized children. The immunogenic potency of vaccine "Bubo-Kok" with respect to all its components was not inferior to that of adsorbed DPT vaccine and vaccine against hepatitis B, when introduced simultaneously in different areas of the body. Vaccine "Bubo-Kok" successfully passed state trials and was recommended for registration.     

Immunity indices during the vaccinal therapy of protracted forms of dysentery in children

The results obtained in the study of the dynamics of systemic and local immunity characteristics in children with prolonged and chronic dysentery under the influence of vaccinal therapy are presented. The vaccine, containing soluble antigenic complexes isolated from Shigella sonnei cells by disintegration with hydroxylamine, was introduced intrarectally in doses of 2-4 mg. The course of treatment consisted of 5-6 administrations. The vaccinal therapy resulted in an increase in the level of immunoglobulins and the titer of specific antibodies, particularly IgA, in sera and fecal filtrates. These data coincided with an increase in the number of IgA-producing cells in bioptic samples of the mucous membrane of the large intestine. The vaccinal therapy contributed to the cessation of the release of bacteria in 82.5% of the patients.     

Reliability of the serological method of examination as a basis for diagnosis of associated respiratory virus infections.

The reliability of the results of serological examination in diagnostics of associated infections was studied on a model of artificially provoked vaccinal infections in humans and in laboratory animals. The effect of administered monopreparations on changes in the level of both homologous and heterologous antibodies was tested. The character of immunological changes following simultaneous administration of two or more respiratory viruses was analysed and the effect of these viruses in diseases of divers etiology was studied. According to the results of experiments on laboratory animals, repeated administration of any of the earlier used respiratory viruses stimulated the accumulation of only homologous antibodies while heterologous antibodies did not increase at all. The results revealed the possibility of simultaneous immunological reorganization of a child's organism in response to the influence of several different antigens from the group of respiratory viruses acting synchronously or in succession. Results of the analysis demonstrated the reliability of the employed serological methods of diagnosis of respiratory virus infections.     

On the dynamics of population changes of plasma cells during antibody formation

The dynamics of changes of the types of all plasma cells and of the antibody-synthesizing cells against the given antigen were studied on regionary lymph nodes of rabbits immunized twice with diphtheria toxoid (staining of sections of the nodes with methyl-green-pyronine and the indirect method of Coons for antibodies). On the basis of comparison of the ratio of young plasma cells to mature plasma cells characteristics of the course of differentiation of plasma cells synthesizing and not synthesizing antibodies were evaluated. It was shown that differentiation of plasma cells does not proceed in the same way in the secondary and primary antibody formation. In the last case, differentiation of antibody-synthesizing cells proceeds differently from cells not synthesizing antibodies. Data obtained on differences in histogenesis of plasma cells are discussed.     

Epidemiological and immunological criteria of the effectiveness of immunization with adsorbed DPT vaccine by the old and new schedules

The study revealed that the immunization of children with adsorbed DPT vaccine from the age of 3-4 months, as compared with the immunization of children from the age of 5-6 months, did not lead to an essential increase in the coverage of children with immunization at the period under study (1970-1983) and did not affect the total level of pertussis morbidity, as well as the proportion of children aged up to 1 year in the total number of pertussis cases. Children immunized at an early age produced antibodies in titers, equivalent to the titers in older children, but their immunity against pertussis, in contrast to their immunity against diphtheria and tetanus, was retained for a shorter period. The injection of adsorbed DPT vaccine at the age of 3-4 months was accompanied by a poorly pronounced increase in the content of IgG, the predominant synthesis of IgM and the suppression of the synthesis of IgA. The shift of the start of vaccination to the age of 3-4 months has probably some immunological grounds for diphtheria and tetanus, but it is premature with respect to pertussis.     

Resistance to a causative agent of infection and immune response

An analytical literature review dealing with the problems of resistance to causative agents of infections. The review includes the data of experimental research, as well as the author's own immunological studies in children at the clinic of acute infections. Mechanisms of resistance at different phases of the infectious process, the multivalued role of Th1- and Th2-dependent responses in different infections, the role of vaccinal immunity in the resistance of children to the causative agents of vaccine-preventable infections (diphtheria and parotitis) are analyzed.     

Prevention of mumps in preschool institutions using a live mumps vaccine made from strain L-3

The effectiveness of the emergency vaccinal prophylaxis of epidemic parotitis was studied in 19 children's day-care centers. As revealed in this study, the immunological effectiveness of vaccination did not depend on the age of vaccinees, but sharply decreased if live parotitis vaccine contained less than 10,000 HADU50 per immunization dose. After a single administration of the vaccine 91.1 +/- 0.98% of children were found to produce mumps antibodies. The immunization of children with live parotitis vaccine prepared from strain l-3 immediately after the first case of parotitis had been registered proved to be a highly effective measure. The coefficient of epidemiological effectiveness was 96.4%.     

Use of immunosorbents for determining antibodies to histaglobulin]

A determination was made of antibodies to histaglobulin and gamma-globulin with the aid of immunosrobents in 178 sera of children suffering from allergic diseases, during the histaglobulin therapy. Results of investigations showed antibodies to histaglobulins to be absent in children untreated by this preparation. But they appeared in 57% of cases after the first course of histaglobulin treatment, and their incidence and their average level increased with an increase in the number of the courses of treatment carried out. gamma-Globulin antibodies were found at the initial condition in 42% of cases; this percentage rose to 68 after the first course of histoglobulin treatment. The authors believe that determination of histaglobulin antibodies during the treatment with this preparation could serve as an auxiliary immunological criterion of the efficacy of histaglobulin therapy.     

Reactions to and immunogenic properties of the combined vaccine Bubo-M for immunization of children against diphtheria, tetanus and viral hepatitis B

Bubo-M, the first Russian combined vaccine, was found to have low reactogenicity. The difference between the number of postvaccinal reactions in the group of children immunized with Bubo-M (25.9%) and those in the group of children who had been simultaneously injected into different sites of the body with ADS-M toxoid (adsorbed DT toxoid with reduced antigen content) and hepatitis B vaccine (26.7%) was not statistically significant. Following immunization a considerable increase in the level of diphtheria and tetanus antibodies (p < 0.005) was observed in all children (100%), the level of HBs antibodies in the group of children immunized with Bubo-M (the geometric mean titer: 13,721 IU/l) essentially exceeding that observed in the control group injected with ADS-M toxoid and hepatitis B vaccine (the geometric mean of the titer: 2,441 IU/l). Bubo-M was duly registered and allowed for industrial production and medical use.     

A calendar of prophylactic inoculations in wide practical use

The validity of immunizations, made in due time in children aged up to 7 years in accordance with the approved immunization schedule, is analyzed in this work. The content of antibodies to diphtheria, tetanus and poliomyelitis antigens in children immunized in accordance with the old and new schedules has been studied. This study has revealed that the injection of adsorbed DPT vaccine to children aged 3-4 months induces fully valid immune response to all antigens under study. The level of measles and parotitis antibodies after the injections of measles and parotitis vaccines, introduced separately and simultaneously, has been measured. The simultaneous administration of these preparations did not decrease the levels of immunity to parotitis and measles.     

Reactivity, immunogenicity and epidemiological effectiveness of vaccination according to various schemes of immunization against whooping-cough, diphtheria and tetanus]

An extended controlled epidemiological trial was carried out for the purpose of studying the reactogenic properties, immunological and epidemiological efficacy of immunization against whooping cough, diphtheria and tetanus according to a scheme suggested by the authors (AKdeltaC-AKdeltaC-KB) in comparison with the official scheme (AKdeltaC-AKdeltaC-AKdeltaC). There was revealed some increase in the frequency of general reactions in children vaccinated by the experimental scheme; however strong general reactions and local reactions of different intensity were encountered with equal frequency in both groups. Two months after the end of the vaccination significantly higher titres of pertussis agglutinins were revealed in children immunized by the AKdeltaC-AKdeltaC-KB scheme; no significant difference was found in the content of the protective titres of diphtheria and tetanus antitoxins. The duration of preservation of postvaccinal antibodies against all the AKdeltaC-vaccine components and increase in their amount after the first revaccination (in 1.5-2 years) was the same in both the groups of children. A greater epidemiological efficacy of pertussis antigen was revealed by prolonged observation in immunization by the AKdeltaC-AKdeltaC-KB sheme in comparison with immunization by the official scheme (pertussis incidence per 100 thousand children proved to be 12.7 and 71.2, respectively).     

Indices of diphtheria (antitoxic) immunity in the dynamics of the disease and its treatment in adults

A total of 1,034 serum samples from 618 persons, including patients with different forms of diphtheria, carriers of the toxigenic forms of Corynebacterium diphtheriae, and angina patients, were studied. Analysis of the incidence of antibodies to C. diphtheriae toxin and their titers revealed that in more than half of all diphtheria patients no antibodies to C. diphtheriae toxin were detected upon admission to hospital. At the same time in 26% of the patients no antibodies were detected during the whole period of the disease; in such patients the toxic and subtoxic forms of diphtheria were registered twice as often as in seropositive patients. In 31% of the patients seronegative by the moment of hospitalization a rapid increase in the titers of antibodies C. diphtheriae toxin was observed in the course of the disease, which was indicative of the secondary character of immune response in patients who had been immunized earlier.     

Analysis of the antigen- and mitogen-induced differentiation of B lymphocytes from asymptomatic human immunodeficiency virus-seropositive male homosexuals. Discrepancy between T cell-dependent and T cell-independent activation

Five asymptomatic human immunodeficiency virus (HIV)-seropositive male homosexuals were immunized with the recall antigens tetanus toxoid (TT) and the three types of poliovirus present in diphtheria, tetanus, and polio vaccine. Four weeks after immunization, the in vivo response to booster immunization, the in vitro pokeweed mitogen (PWM)-induced IgG secretion, and the in vitro T cell-dependent and T cell-independent antigen-induced antibody response were assayed. Increase in serum antibody titer to TT and poliovirus was low and normal, respectively. In all five subjects studied, a high rate of spontaneous IgG production, including antibodies directed toward HIV was observed. Addition of PWM to the cultures induced suppression of the spontaneous IgG secretion. Only one donor showed a slightly increased IgG production after stimulation with PWM. Peripheral blood mononuclear cells of four of the five HIV-seropositive individuals did not produce TT, or poliovirus-specific antibodies when stimulated with the respective T cell-dependent antigens. However, stimulation of these peripheral blood mononuclear cells with TT coupled to agarose beads, which was shown to be T cell-independent, resulted in the generation of IgG anti-TT antibody-forming cells.     

Cytotoxic antibodies to thymocyte antigens in rheumatism and other diseases

Cytotoxic antibodies reacting with mouse and human thymocytes were detected in rheumatic patients' sera. The level of cytotoxic antibodies was considerably higher in active than in inactive process. A correlation was found between the antibody level and the clinical course of rheumatic fever. The cytotoxic index was the highest in sera of patients with acute rheumatic fever. Thymocytotoxic antibodies were also found in other autoimmune diseases. In sera of normal individuals, antibodies to thymocytes were revealed rarely and in small quantities. A possible role of thymocytotoxic antibodies as a cause of deficit of T suppressors in autoimmune diseases is discussed.     

Contents of antibodies to Bordetella pertussis antigens in patients with rheumatic diseases

Study of presence of antibodies against pertussis in 72 rheumatic patients (with uvenile rheumatoid arthritis, systemic lupus erythematosus, etc.) aged 1-18 year old without history of pertussis was performed. Mean age of the patients was 10.6 +/- 0.48 year old, duration of illness--51.2 +/- 4.42 months. Immunosupressive therapy at the time of the study was conducted in 68 (94.4%) children. Using ELISA method, IgG to pertussis toxin (PT) and to antigens of acellular pertussis vaccine (aPV) were detected in 98.6% and 100% of children. High titers of antibodies were detected more frequently in 7-18 year old age group, which can indicate recent pertussis disease or infection. Vaccination history was studied in 131 children with rheumatic diseases. Incidence of pertussis in 43 unvaccinated children was 116.3 per 1000, and in 16 children with incomplete vaccination--62.5 per 1000. Out of 75 patients, who received vaccination series and revaccination, clinically distinct pertussis was not diagnosed.     

The immunological effectiveness of small doses of diphtheria and tetanus anatoxins in the revaccination of children with allergy-altered reactivity and adults

The possibility of decreasing the content of antigens in adsorbed diphtheria-tetanus toxoid, used for the booster immunization of children with allergically altered responsiveness and adults, is shown. Diphtheria toxoid in doses of 1-2.5 Lf and tetanus toxoid in doses of 1-2.5 binding units possessed sufficiently high immunological effectiveness in combination with low reactogenicity and good tolerance. In 6-12 months after booster immunization with decreased doses of toxoids 100% of children with allergy of different character and, respectively, 86-94% and 95% of adults have developed protective levels of antibodies to diphtheria and tetanus.