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.     

Comparative immunologic effectiveness of variants of the DTP vaccine

The immunological effectiveness of two batches of adsorbed DPT vaccine, the batch with the normal content of antigens (control) and the batch with the content of diphtheria and tetanus toxoids reduced to 20 Lf/ml and 5 BU/ml respectively (test batch), has been studied under the conditions of controlled trial. As a result, the reduction of the antigenic content of adsorbed DPT vaccine has been found to exert no negative influence on the immunological effectiveness of the diphtheria, tetanus, and pertussis components of this preparation under the conditions of the new immunization schedule.     

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.     

Duration of immunity in children who received a primary complex of inoculations with ADT-M anatoxin and an assessment of postponed secondary revaccination against diphtheria and tetanus (the results of an epidemiologic trial)

The prolonged observations of the immunological effectiveness of adsorbed diphtheria-tetanus toxoid with reduced antigen content in children who had received the primary course of immunization with this preparation showed that the preparation induced the development of prolonged and intensive immunity to both infections. In 2-3 years after the first booster immunization the protective level of diphtheria antitoxin was registered in 89.9% and that of tetanus antitoxin, in 99% of children. 6 years later the level of immunity remained practically unchanged: the titers of diphtheria antitoxin above the protection level were determined in 92% and those of tetanus antitoxin, in 97% of children. These data made it possible to increase intervals between booster immunizations to 6-7 years in children of this category. The results of the epidemiological trial made to find out the possibility of a change in the timing of the second booster immunization confirmed the expediency of postponing booster immunization from 6 and 11 years to 9 and 16 years of age.     

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.     

The antidiphtheria and antitetanus immunities of children of the Maritime Territory after the use of adsorbed DTP vaccine and adsorbed DT-m anatoxin]

The state of collective immunity to diphtheria and tetanus in children of preschool age, depending on the kind of vaccine preparation used for immunization, was studied. The immunological potency of adsorbed DPT vaccine (i.e. its capacity of forming prolonged and stable basic immunity) was shown to be higher in comparison with the potency of adsorbed DT toxoid with reduced antigen content (DT-R). The study revealed that in all groups of children the level of antitetanus immunity was higher than the level of antidiphtheria immunity, and 3 years later its decrease was less pronounced. A stricter approach to giving medical grounds for the use of low-reactive adsorbed DT-R in the immunization of children belonging to groups of risk is recommended.     

The specific prophylaxis of diphtheria in adults with adsorbed DT-m anatoxin]

The dependence of immune response on commonly observed immunity characteristics prior to immunization has been established on the basis of the study of the kinetics of immune response in adults receiving injections of adsorbed diphtheria-tetanus (DT) toxoid with reduced antigen content, both for routine immunization and on epidemiological indications. The necessity of the practical use of immunological screening for the differentiated approach to the choice of a suitable preparation (adsorbed diphtheria toxoid, adsorbed DT toxoid or adsorbed DT toxoid with reduced antigen content) and immunization schedule for adults, especially in epidemic foci, has been substantiated.     

Immune response in adult immunized with adsorbed DT-M anatoxin with reduced antigen content and Imovax-DT-adulte vaccine

The comparative study of immune response after immunization of adults with adsorbed DT toxoid with reduced antigen content and Imovax-DT-adulte vaccine, as well as the safety of these preparations, was made. The study revealed that immunization of adults with adsorbed DT toxoid having reduced antigen content, made in two injections, and the injection of Imovax-DT-dulte vaccine, as well as the successive injection of these preparations, produced the same the levels of antitetanus immunity. Antidiphtheria immunity, evaluated by the number of seroconverted to diphtheria persons following two injections immunization was similar for the two preparations, while the level of antidiphtheria antibodies was higher in persons immunized with adsorbed DT toxoid. The immune stratum index was rather high among persons aged 16-29 years. This age group exhibited the highest number of persons, seropositive to both diphtheria and tetanus. Both vaccine preparations, adsorbed DT toxoid with reduced antigen content and Imovax-DT-adulte vaccine, were found to be equally capable of inducing autoimmune reactions in the vaccinees, detected by laboratory methods.     

Reactogenic properties of a DTP vaccine with a reduced antigen dosage

The reactogenic properties of batches of adsorbed DPT vaccine with the normal content of antigens and with the content of diphtheria and tetanus toxoids reduced, respectively, to 10 Lf and 5 BU per immunization dose have been studied under the conditions of a controlled epidemiological trial. The reduced antigenic content of adsorbed DPT vaccine decreased the number of vaccinal reactions 1.8 times, as well as the intensity of their manifestations.     

Immunological effectiveness of secondary revaccination against tetanus performed at prolonged intervals

After primary immunization with adsorbed DPT vaccine antitetanus immunity was retained for 9-10 years in 90.6-98.4% of children covered by this study. The second booster immunization of children against tetanus with adsorbed DT toxoid with reduced antigen content, made at an interval prolonged to 7-10 years under the conditions of lower antitoxic immunity, ensured a high level of intense antitetanus immunity. These data point to the possibility of prolonging the interval between booster immunizations to 9-10 years and reducing the number of injections and antigenic load.     

Diphtheria-tetanus overimmunization in children with no records: can it be prevented?

A pilot study was undertaken to assess the validity of two new tests for predicting the immune response of Toronto schoolchildren with no acceptable evidence of prior administration of diphtheria or tetanus toxoid to a routine booster injection of diphtheria and tetanus (DT) toxoid. The tests, an inexpensive enzyme-linked immunosorbent assay (ELISA) fingerprick test for tetanus antibodies and a modification of the Schick skin test for susceptibility to diphtheria, were administered before the booster injection. One week later the ELISA test was repeated and the result of the modified Schick test read. On both occasions a diphtheria microneutralization assay was done for "gold standard" evidence of prior exposure to diphtheria toxoid or toxin. The results were used to determine the sensitivity and specificity of a single prebooster tetanus ELISA test or a modified Schick test for predicting which children with no records could be safely protected with only one DT booster dose instead of the primary series of three or four doses usually given to such children. Only 6 of the 34 subjects (18%) were totally without prior exposure to tetanus toxoid. Two of the six (6% of 33 subjects) appeared to mount a primary immune response to diphtheria toxoid as well. An initial ELISA titre of 0.01 IU/ml or lower correctly identified all six children needing a full series of tetanus toxoid (sensitivity for a primary immune response 100%) and falsely identified only 3 of 28 immune children as needing the series (specificity for immunity 89.3%). The modified Schick test appeared to have even greater accuracy for identifying children needing a full series of diphtheria toxoid. However, its use, entailing the costs of an extra nurse visit, would have prevented only seven more children from receiving an unnecessary full series of diphtheria toxoid than use of the baseline tetanus ELISA test alone.     

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.     

The ecological aspects of ADTP vaccination]

The results of measuring the activity of diphtheria and tetanus toxoids in the blood of 19,654 persons immunized with adsorbed DPT vaccine have shown a pronounced decrease in the effectiveness of booster immunization with adsorbed DPT vaccine. The negative influence of environmental pollution is more pronounced with respect to less active diphtheria toxoid. The possibility of the separation of the population into strata differing in the intensity of their immune response to toxoids under the influence of environmental pollution is considered.     

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.     

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.     

Immunological effectiveness of a 2d revaccination against diphtheria performed at intervals extended up to 7-10 years

The present article deals with the data on the duration of antidiphtheria immunity, induced by the primary cycle of immunization with adsorbed DPT vaccine, with the aim of considering the problems of optimizing the immunization schedule for children. The prolongation of the interval before the second booster immunization to 7-10 years produces no negative influence on the effectiveness of immunization. Besides, the study has shown that after the main complex of immunizations with adsorbed DPT vaccine protective immunity to diphtheria is retained in 90.3-96.8% of children covered by this study for 9-10 years. These data point to high immunological effectiveness of adsorbed DPT vaccine and to the possibility of prolonging the intervals between booster immunizations to 10 years, as well as decreasing the number of booster immunizations in the immunization schedule for children.     

Alternative diphtheria, tetanus and whooping cough immunization schedule to evoke a Th2 tetanus and a Th1 pertussis immune response

In a previous study, using BALB/c mice, we found that while diphtheria (D), tetanus (T) and whooping cough (Pw, whole-cell Bordetella pertussis) immunization induces a Th1/Th2 tetanus response and memory T cells able to proliferate in response to in vitro stimulation with B. pertussis, DTPa immunization induces a Th2 tetanus immune response and no memory T cells that recognize B. pertussis as stimulus. Considering that a pro-inflammatory cytokine production is not necessary for protection against tetanus and therefore should be avoided, an alternative DTP immunization schedule with minimal Pw exposure was assessed in order to obtain a Th2 tetanus response and a Th1 pertussis response. BALB/c mice were primed with DT vaccine at day 0, with Pw vaccine at day 14 and boosted with DTPa vaccine at days 21 and 28. A control group was inoculated with saline. Antibodies against B. pertussis surface antigens, tetanus and diphtheria toxoids were produced by mice. Spleen cells stimulated in vitro with B. pertussis produced IL-6 and IFNgamma. Only IL-5 was produced by cells in response to tetanus toxoid stimulation. These results are in line with the low IgG1/IgG2a ratio for pertussis antibodies compared with those corresponding to tetanus and diphtheria. The immunization protocol presented herein succeeded in producing tetanus and pertussis immune responses of Th2 and Th1 type, respectively. In contrast to previous results obtained with DTPw immunization, no IL-12 production was observed. Our findings provide direct evidence that an immunization protocol with an interval of 14 days between DT and Pw primings, followed by DTPa boosters, can induce appropriate immune responses against DTP vaccine antigens.     

The immunization of adults against diphtheria in Sweden

Two hundred and three women who disclaimed vaccination against diphtheria were divided into four groups and injected with either 2.0 or 6.25 Lf of a routine diphtheria toxoid or of a more purified preparation. One hundred and twenty-six of these women who did not show a secondary antibody response were given a second and a third injection one month and one year, respectively, after the first injection. Prebooster (third injection) antitoxin titres of greater than or equal to 0.01 IU ml-1 (the minimum level for protection) were found in 22 and 37% of those who received 2.0 and 6.25 Lf, respectively. Postbooster titres of greater than or equal to 1.0 IU ml-1 (calculated to give a protection of at least ten years of duration) were found in 23 and 58% of those who received 2.0 and 6.25 Lf, respectively. The rate of untoward reactions was low. Fever of short duration occurred in five women. Four out of the five women received 6.25 Lf of the more purified diphtheria toxoid and one 2 Lf of the routine toxoid. Local reactions greater than 10 cm were observed in three women. All received the higher dose, 6.25 Lf of diphtheria toxoid. Local reactions greater than 5 but less than or equal to 10 cm occurred in up to 13% (6.25 Lf of diphtheria toxoid). No significant difference between the groups of women vaccinated with routine or more purified toxoid was found. It was concluded that the diphtheria toxoids in the two doses of 2 Lf and 6.25 Lf did not induce a satisfactory immune response. To induce adequate protection the dose of diphtheria vaccine needs to be the same for adults and children, i.e. 12.5 Lf.     

关于吸附精制百日咳菌苗、白喉、破伤风类毒素混合制剂配方的实验报告

本文对吸附精制百白破混合制剂的不同配方进行了实验,结果表明,新一代吸附精制百白破混合制剂最佳配方为：精制百日咳菌苗１８μｇＰＮ／ｍｌ、精制白喉类毒素为３０Ｌｆ／ｍｌ、精制破伤风类毒素为１０Ｌｆ／ｍｌ。由该配方组成的吸附精制百白破混合制剂,其中百日咳菌苗的毒性试验ＢＷＤＵ／ｍｌ、ＬＰＵ／ｍｌ、ＨＳＵ／ｍｌ三种指标均符合制检规程要求。其效力单位（ＩＵ／ｍｌ）超过规程要求一倍以上,精制白喉和破伤风类毒素的安全试验均符合规程要求,白类效力试验≥８０－１００％,破类效力试验≥０．５－４．５ＩＵ／ｍｌ。上述结果说明本文提出的配方作为新一代精制百白破混合制剂的配方是适宜和实用的。     

Whole-cell Bordetella pertussis vaccine component modulates the mouse immune response to an unrelated soluble antigen

Several factors are involved in the selective activation of Th1 or Th2 cells, such as different physical characteristics of antigens and the type of antigen-presenting cells involved in the immune response, among others. To study the influence of a particulate antigen on Th1/Th2 cell differentiation during the immune response to another antigen, we analysed the immune response to tetanus toxoid (soluble antigen) in BALB/c mice immunized with one of the three following vaccines: tetanus and diphtheria toxoids (DT), or DT associated with whole-cell Bordetella pertussis or its soluble antigens (DTPw and DTPa, respectively). Similar total antibody levels were observed for all vaccines. DT vaccine showed a higher IgG1/IgG2a ratio than the similar values observed for DTPw and DTPa vaccines. DT- and DTPa-primed spleen cells showed a Th2 (IL-5) profile while a Th1/Th2 (IFN gamma, IL-5) profile was observed for DTPw. IL-6 was only produced by DTPw-primed cells. Besides, IL-12 levels induced by DTPw were three times higher than the ones induced by both DT and DTPa. Our findings indicate that whole-cell B. pertussis priming modifies the tetanus immune response from Th2 to Th1/Th2 type probably via inflammatory mechanisms. In addition, in the light of conflicting reports regarding the mechanisms of protection induced by DTP vaccines, we studied the pertussis immune response. Only DTPw immunization generated memory T cells capable of proliferating with B. pertussis as an in vitro stimulus. Results might indicate that these cells may not play a key role in protecting against B. pertussis when the host is vaccinated with DTPa.