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.     

Evaluation of postvaccinal pertussis immunity by using immunoenzyme analysis

The effectiveness of adsorbed DPT vaccine manufactured in the USSR, evaluated by its capacity of inducing the formation of the main classes of immunoglobulins and by the duration of immune response to the acellular complex of protective antigens (pertussis toxin and agglutinogen-2), was studied with the use of modified EIA. Out of 273 children immunized with adsorbed DPT vaccine in the course of this study, 87.2% had IgG-antibodies, 14.1% had IgA-antibodies and 3.2% of the children had IgM-antibodies. The level of immunity in children having received the full course of immunization with adsorbed DPT vaccine was significantly higher in comparison with children given only the primary course of immunization and nonimmunized children of the same age. Antipertussis immunity was found to decrease two years after the completion of the course of immunization with adsorbed DPT vaccine and in children over 5-6 years of age. Adsorbed DPT vaccine prevented the disease, but not infection. The level of postinfection immunity was higher than that of postvaccinal immunity.     

Limited controlled trial of the reactogenic properties of ADTP vaccines containing stab cultures as the pertussis component

The reactogenic properties of adsorbed DPT vaccine containing Bordetella pertussis cultures, grown by submerged cultivation, as the pertussis component were studied. The study revealed that the vaccine was low-reactogenic: no severe postvaccinal reactions were recorded in immunized children. The frequency and intensity of febrile and local reactions in children immunized with adsorbed DPT vaccine under trial and the commercial preparation commonly used in the USSR were identical, but considerably less pronounced than in children immunized with foreign vaccines having similar composition.     

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.     

Comparative study of the immunoglobulins and specific antibodies in the blood of rabbits immunized with ADTP vaccine and ADT-anatoxin with normal and reduced antigen contents

Adsorbed DPT vaccine and adsorbed DT toxoids with normal and reduced antigen content were used for the immunization of rabbits. The levels of IgM and IgG and the dynamics of antibodies to diphtheria and tetanus toxins and to Bordetella pertussis in the blood sera of the animals were studied in the postvaccinal period (on days 15 and 34). This study revealed that the reduction of the antigen content of adsorbed DT toxoid to 5 Lf of diphtheria toxoid and 5 binding units of tetanus toxoid did not decrease the capacity of the preparation for increasing the levels of IgG and IgM, antibodies to diphtheria and tetanus toxins in the sera of the rabbits. The reduced content of these toxoids in adsorbed DPT vaccine did not affect its capacity for inducing the enhanced synthesis of IgG, antibodies to diphtheria and tetanus toxins, while the production of IgM and IgA remained unchanged. At the same time an increase in the titers of antibodies to B. pertussis in the animals was less pronounced than that observed after the injection of commercial adsorbed DPT vaccine. Additional investigations are necessary in order to establish the protective potency of the pertussis component in adsorbed DPT vaccine with the reduced content of toxoids and to find out the optimum antigenic composition for this preparation.     

A comparative evaluation of the immunological efficacy of ADPT vaccine and ADT-M anatoxin in the immunization of children against diphtheria and tetanus

Comparative study of the immunological effectiveness of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine and adsorbed diphtheria-tetanus toxoid with reduced antigen content (adsorbed DT toxoid R) in the immunization of children, carried out in accordance with the vaccination schedule, was made. Immune response to the injection of adsorbed DPT vaccine was higher than after immunization with adsorbed DT toxoid R, as evidenced by antibody titers. It was probably due to differences in the number of injections constituting the course of immunization: it consisted of 3 injections and 1 booster injection for adsorbed DPT vaccine and 2 injections and 1 booster injection for adsorbed DT toxoid R. Immunization with adsorbed DPT vaccine produced immunity which was retained for a longer period. These results are indicative of the expediency of the primary immunization of children with adsorbed DT toxoid R introduced in three injections in order to ensure more stable and prolonged postvaccinal (mainly antidiphtheria) immunity.     

Evaluation of reactogenicity and immunogenicity of Bubo-M, the Russian combined vaccine for immunization of adults against diphtheria, tetanus and viral hepatitis B

Bubo-M, the first Russian associated vaccine, was found to have low reactogenicity and high immunogenic potency. The frequency of postvaccinal reactions in the group of persons immunized with Bubo-M (20%) appeared to be considerably lower than among persons who received the combined injection of adsorbed DT toxoid with reduced antigen content and vaccine against hepatitis B (47.7%). Following the course of vaccination the level of anti-HBs considerably exceeded the protective level. Immune response to the diphtheria and tetanus components of Bubo-M exceeded that observed after immunization with absorbed DT toxoid with reduced antigen content (p < 0.05).     

Antigenic similarity of the pertussis component of adsorbed DTP vaccine to human erythrocytes

The similarity of the heterogeneous antigens, types A and B, of human red blood cells to the most of B. pertussis strains constituting the pertussis component of commercial batches of adsorbed DPT vaccine has been established. This property makes the vaccine strains different from B. pertussis isolated from pertussis patients. One of the reasons of the insufficient effectiveness of immunization against pertussis has been determined: the intensity of immune response depends on the antigenic heterogeneity of the pertussis component of the vaccine and the AB0 group factors in the blood of the vaccinees. For the first time the accumulation of immune alpha- and beta-isoagglutinins in the blood of persons immunized with absorbed DPT vaccine has been established. This accumulation shows the medium degree of direct correlation with the manifestations of the clinical reaction to the injection of the vaccine. The data obtained in this study indicate the necessity to revise the existing method of obtaining the pertussis component of adsorbed DPT vaccine on solid culture media with human red blood cells added and to develop the technique of the additional purification of this component from heterogeneous antigens.     

Antipertussis immunity studied by immunoenzyme analysis

The levels of antibodies to disintegrated Bordetella pertussis and its individual fractions (protein and polysaccharide) in children immunized with different batches of adsorbed DPT vaccine have been determined with the use of EIA techniques. The background level of antibodies in the control groups has been determined, and in immunized children the levels of antibodies to disintegrated B. pertussis and its protein fraction have been shown to considerably exceed the levels of antibodies to lipopolysaccharide.     

The evaluation of the efficacy of a first course of immunization against diphtheria and tetanus in children with kidney diseases

The results of the determination of the level of antitoxic antibodies (Ab) to diphtheria and tetanus toxoids in children with glomerulonephritis and pyelonephritis are presented. The influence of the form of the disease and the kind of medicinal therapy on level of specific Ab has been studied. As shown in this study, the injection of adsorbed DT toxoid with reduced antigen content leads to the formation of the protective titers of antidiphtheria and antitetanus Ab, but a lower level than after the injection of adsorbed DPT vaccine.     

不同来源血浆对静注人免疫球蛋白中抗-HBs、白喉抗体效价的影响

调查分析不同来源原料血浆对静注免疫球蛋白(IVIG)制品内的抗-HBs、白喉抗体效价的影响。选择6个单采血浆站,对其提供的血浆为原料制备的IVIG所含的抗-HBs抗体、白喉抗体效价进行了测定。检测结果显示,用A、B、C、D、E、F编号的6个相应血浆站采集的血浆为原料制备成IVIG其抗-HBs抗体(IU/g)效价分别为33.77、103.95、70.94、132.45、78.84、58.28;白喉抗体平均效价分别为5.17、7.36、4.26、7.67、10.14、9.24。6个单采血浆站间的IVIG制品中白喉抗体效价无明显差异,但抗-HBs效价却存有显著差异。     

Humoral imunity to pertussis in children with diabetes of type 1

To determine the state of humoral immunity to pertussis in children with insulin-dependent diabetes, IgG antibodies to pertussis toxin (PT) were determined in blood serum samples by means of EIA. In a group of children aged up to 6 years the highest percentage (100%) received the complete course of vaccination against pertussis with Russian adsorbed DPT vaccine, containing whole-cell pertussis monovaccine, while in a group over 6 years the complete vaccination course (3 vaccinations and 1 revaccination) had 53.4% of children. Pertussis morbidity was considerably higher in nonvaccinated subjects than in children with 4-fold vaccination (p < 0.001). The coefficient of association (Q) was 0.84. Children of all age groups were found to have low and average titers of antibodies to PT. The regressive analysis showed a decrease in antibodies in persons completely immunized against pertussis by the age of 6 years old. The presence of antibodies in nonimmunized persons showed that cases of pertussis or carrier state took place among the population. High titers of antibodies, indicative of recent cases of pertussis, were registered in all age groups, but high titers of antibodies were registered mostly in the group of children over 13 years old (p < 0.05), which confirmed an increase in pertussis morbidity in adolescents. Thus, vaccination against pertussis effectively protected children with diabetes of type 1, aged up to 6 years. For more prolonged protection the vaccination and revaccination of children aged over 4 years old is necessary.     

Experience with vaccine prophylaxis of hepatitis B among different groups of children

The immunological activity of different vaccines against hepatitis B was evaluated in the Hepatological Center organized on the basis of the Infectious Hospital in Tula. Newborn infants were immunized with the use of the following vaccines: Engerix B (Belgium), Combiotech (Russia), Euvax B (Aventis Pastèur, South Korea). Altogether, after the full course of immunization anti-HBs were detected in 76 children out of 81 (in 93.8%). Vaccine Engerix B, when introduced according to the schedule 0-1-2-12 months, exhibited high immunogenic properties in a group of infants born of women with persistent HBs-antigenemia. Anti-HBs at a concentration exceeding 1000 I.U./I could be detected in 84.6%. In another group of children immunized according to the schedule 0-1-6 months first with vaccine Combiotech at the age of 0 and 1 month, then (at the age of 6 months) with vaccine Euvax, the presence of postvaccinal anti HBs at protective concentration was registered in all children. After immunization against hepatitis B with the use of all above-mentioned vaccines introduced according to both schedules high immunological activity and safety of immunization were noted.     

The effect of histamine on the rosette-forming ability of T-lymphocytes upon immunization with DPT vaccine and its components

The influence exerted by histamine on the capacity of T-lymphocytes for spontaneous rosette formation in intact animals and in animals immunized with adsorbed DPT vaccine and its components has been studied. Histamine at a concentration of 10(-3) M has been found to produce an inhibitory effect on the capacity of lymphocytes in the blood and spleen of guinea pigs immunized with adsorbed DPT vaccine and its components for spontaneous rosette formation. This effect of histamine has proved to be even more pronounced after the immunization of the animals with adsorbed DPT vaccine and Bordetella pertussis suspension, which is probably due to their sensitizing action.     

Evaluation of the immune response to hepatitis B vaccination in children aged 1-3 years in Malatya, Turkey

By the end of 1998, Turkey had launched the routine vaccination of infants against hepatitis B. The purpose of the study is to evaluate the immune response in a sample of vaccinated children aged 1-3 years in the city of Malatya. A total of 210 vaccinated children 12 to 48 months old were selected for the study with 30 cluster sampling in the city of Malatya, Turkey. The children were visited at their homes during January-April 2002. The information on demographic characteristics, family's and child's medical history was gathered, childrens' weight and height were measured and blood samples were taken. Anti-HBs, HbsAg and anti-HBc titers were assayed by micro-ELIZA from the sera. The mean age of the children was 26.3 months, 100 (47.6%) were male and 110 (52.4%) were female. Overall, 203 (96.7%) children had protective anti-HBs levels (> or = 10 IU/l), 0.5% showed evidence of natural infection (with positive anti-HBc and anti-HBs titers), 0.5% had acute or chronic infection (with positive HbsAg and anti-HBc titers) and 2.3% were seronegative. Geometric mean titer of anti-HBs among vaccinated children except those who had positive anti-HBc titers was 138.7 mIU/ml (95% CI:124.7-154.2) and seroconversion rates did not differ by age, sex, anthropometric measurements, time after third dose and place of vaccine administered (P > 0.05). The high seroprotection rate over 95% showed that routine infant vaccination program for hepatitis B was successfully carried out in the city Malatya.     

Matrix-M™ adjuvation broadens protection induced by seasonal trivalent virosomal influenza vaccine

Background

Influenza virus infections are responsible for significant morbidity worldwide and therefore it remains a high priority to develop more broadly protective vaccines. Adjuvation of current seasonal influenza vaccines has the potential to achieve this goal.

Methods

To assess the immune potentiating properties of Matrix-M?, mice were immunized with virosomal trivalent seasonal vaccine adjuvated with Matrix-M?. Serum samples were isolated to determine the hemagglutination inhibiting (HAI) antibody titers against vaccine homologous and heterologous strains. Furthermore, we assess whether adjuvation with Matrix-M? broadens the protective efficacy of the virosomal trivalent seasonal vaccine against vaccine homologous and heterologous influenza viruses.

Results

Matrix-M? adjuvation enhanced HAI antibody titers and protection against vaccine homologous strains. Interestingly, Matrix-M? adjuvation also resulted in HAI antibody titers against heterologous influenza B strains, but not against the tested influenza A strains. Even though the protection against heterologous influenza A was induced by the adjuvated vaccine, in the absence of HAI titers the protection was accompanied by severe clinical scores and body weight loss. In contrast, in the presence of heterologous HAI titers full protection against the heterologous influenza B strain without any disease symptoms was obtained.

Conclusion

The results of this study emphasize the promising potential of a Matrix-M?-adjuvated seasonal trivalent virosomal influenza vaccine. Adjuvation of trivalent virosomal vaccine does not only enhance homologous protection, but in addition induces protection against heterologous strains and thus provides overall more potent and broad protective immunity.

     

Effect of histamine on the rosette-forming capacity of T-lymphocytes in immunization with ADPT vaccine and its components

The results obtained in the study of the influence of histamine on the capacity of T-lymphocytes of guinea pigs immunized with DPT-vaccine and its components for spontaneous rosette formation are presented. Histamine at a concentration of 10(-3) M has been found to inhibit the capacity of blood and splenic lymphocytes of guinea pigs immunized with adsorbed DPT vaccine for spontaneous rosette formation. The inhibitory effect is more pronounced after the immunization of the animals with adsorbed DPT vaccine and Bordetella pertussis suspension.     

The level of postvaccinal immunity to diphtheria, tetanus and poliomyelitis in relation to the number of inoculations]

The work was aimed at the comparative study of the intensity of immunity to diphtheria, tetanus and poliomyelitis, depending on the number of injections of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine and poliomyelitis vaccine, for the purpose of finding out the possibility of reducing the antigenic load given to children without diminishing the intensity of immunity. To determine the level of immunity to diphtheria and tetanus, 1900 children under school age were serologically studied by the micromethod in the passive hemagglutination test. The intensity of immunity to poliomyelitis virus was studied in 333 children by means of the neutralization test. The immunogenic properties of the diphtheria component of adsorbed DPT vaccine were found to be less pronounced than those of the tetanus component of the vaccine, which made it impossible to reduce the antigenic load by decreasing the number of vaccinations against diphtheria. The results of the study of postvaccinal immunity to poliomyelitis suggest that during the first and second year of life the course of vaccination against poliomyelitis may be reduced to 3 injections.     

Clinical and immunological effect of vaccination against Haemophilus influenzae, type B, in children with disorders of the nervous system

Observations on 277 children aged 3 months to 4 years with lesions of the nervous system, immunized with vaccine Act-HIB (Aventis Pasteur, France), were carried out in groups of children. The significant decrease of the level of Hib nasopharyngeal carrier state in 3.3 times and the decrease of total morbidity in acute infections of respiratory and ENT organs in 2.7 times occurred after immunization was revealed. The immunological effect of immunization on the level of protective titers against H. influenzae, type b, in children with organic CNS lesions in children was shown.     

The characteristics of the development of immunity with a primary immunization complex using adsorbed DTP vaccine

The intensity of immunity, depending on immune response variants characterized by the definite composition of the T and B lymphocyte subpopulation in peripheral blood, was studied in 70 practically healthy young children after the primary complex of immunization with adsorbed DPT vaccine. The most stable immune reaction was shown to appear in children with the hyperergic and normoergic variants of immune response to diphtheria and tetanus toxoids, while the reaction to pertussis antigen was essentially weaker both after the second vaccination and after the first revaccination. In children with the hypoergic variant of immune response to all components of adsorbed DPT vaccine the resulting immune reaction was 2.5-3 times weaker than in children of other groups.