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.     

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.     

Vaccination of children under immunosuppressive therapy with ADS-m anatoxin

The effectiveness and safety of the immunization of children with adsorbed DT toxoid with reduced component with disturbances in the reactivity of the body, caused by immunosuppressive therapy, are evaluated. The group under study included 53 children with glomerulonephritis, malignant tumors and acute lymphoblast leucosis, formerly receiving immunosuppressive drugs. The control group consisted of 24 patients with pyelonephritis who had not received such therapy. In the postvaccinal period no exacerbation of the main disease was registered in children. The manifestation and frequence of postvaccinal reactions did not differ from those observed in healthy children after the injection of adsorbed DT toxoid with reduced antigen content. Control serological testing demonstrated the presence of pronounced immune response in the vaccinees.     

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).     

Use of adsorbed diphtheria-tetanus (DT) toxoid containing different doses of antigens in booster immunizations of children

To decrease the antigenic load in booster immunizations of children against diphtheria and tetanus, the immunological effectiveness and reactogenicity of different doses of both antigens (i. e 1 Lf and 1 BU; 2.5 Lf and 2.5 BU; 5 Lf and 5 BU) were studied. The study revealed that all these doses of the preparation were practically nonreactogenic: the total of systemic reactions was 0.9%. The study of the immunological effectiveness of adsorbed DT toxoid with reduced antigen content revealed the advantage of the commercial dose of the preparation (5 Lf of diphtheria antigen and 5 BU of tetanus antigen) over such doses of diphtheria and tetanus antigens as, respectively, 1 Lf and 1 BU; 2.5 Lf and 2.5 BU. Still, this advantage disappeared as early as 6 months after booster immunization. The results of these investigations indicate that booster immunization of children aged 6 years and over may be made with lower doses of adsorbed DT toxoid with reduced antigen content.     

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.     

Antidiphtheria immunity in adult population of the Orenburg region

The analysis of the level of antidiphtheria immunity in different age group of the adult population has shown that postvaccinal immunity resulting from immunization with adsorbed DT toxoid with reduced antigen content gradually decreases after the period of two years. The immune stratum remains sufficiently numerous only among persons aged 18-27 years (93.3%), persons over 38 years constitute a high risk group with respect to the possibility of diphtheria infection: the proportion of persons protected against this infection amounts to 71.3% in the age group of 38-47 years and 54.9% in the age group over 48 years, that is not sufficient.     

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.     

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.     

Stimulating Role of Toxoids-laden Liposomes in Oral Immunization against Diphtheria and Tetanus Infections

Liposomes have been produced by injecting an ether solution of a mixture of lecithin and cholesterol into a diluted solution of prewarmed diphtheria and tetanus toxoids followed by elimination of the stream of ether vapour by vacuum.In a preliminary study, adjuvant effects of liposomes on the systemic and mucosal immune response have been studied. When a mixture of diphtheria toxoid (DT) and tetanus toxoid (TT) entrapped in liposomes were administered parenterally or orally in rabbit, a significant rise of specific antibodies against both toxoids was noticed. In monkeys receiving a mixture of DT and TT entrapped in liposomes orally, the antibody response after two and three ingestions of this product was mild but when liposomes containing toxoids were adsorbed with aluminium hydroxide in a similar experiment, a significant rise in the specific antibody response in monkey against both toxoids was recorded. Adult volunteers, similarly receiving a mixture of DT and TT, entrapped in liposomes and adsorbed with aluminium hydroxide have shown a significant rise in specific circulating antitoxins. In order to compare the efficacy of this technique of human oral immunization with the previous method, whereby a plant medicinal seed (LRS) was used as adjuvant in oral immunization of man, a second group of volunteers were simultaneously and similarly treated as suggested previously. The comparative results are discussed in the present report.     

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.     

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.     

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.     

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.     

Combined Active-Passive Immunization Against Tetanus in Man

A schedule for the prevention of tetanus in the injured, which has been in operation in the emergency department of a large hospital for over two years, is proposed. For the majority of nonimmunized persons, it is recommended that a dose of toxoid and 50 units tetanus immune globulin (human) (TIGH) be given, in separate sites, to be followed later by additional doses of toxoid for the completion of active immunization. Combined active-passive immunization with tetanus toxoid and 50 units TIGH gives a low level of passive immunity and stimulates early onset of active immunization. In combined active-passive immunization, adsorbed tetanus toxoid produced a significantly higher response than the fluid toxoid. The injection of 400 units TIGH somewhat suppressed the induction of immunity following the first dose of AlPO₄-tetanus toxoid.     

The revaccination against diphtheria and tetanus with adsorbed DT-m anatoxin of children having solid tumors in their case histories

Data on the safety and effect of the vaccination of children with solid tumors are presented. As revealed in this study, the injection of adsorbed DT-m toxoid with reduced antigen content at the period of remission does not induce the relapse of the disease and leads to the production of specific antitoxic antibodies on the protective level. The study has shown that complex antitumor treatment does not essentially affect the formation of specific immune response, though prolonged changes in cell-mediated immunity can be observed.     

Morphological bases for the resistance of the intestines to the action of cholera toxoid

Effect of antigen (cholera toxoid) has been studied on distribution of specific antibody-containing plasma cells in the lamina propria of the mucous membrane of the guinea pig small and large intestine. Since it is known that experimental cholera is easily reproduced in these animals, amount of plasmocytes is determined after primary intraperitoneal and secondary intraduodenal immunization with cholera toxoid. At the primary immunization maximal increase in amount of plasmocytes is noted in the jejunum on the 70th day; at the secondary--on the 19th day. At the primary parenteral immunization of the animals with the antigen, the intensity of the immune response in the lamina propria of the mucous membrane increases. At the secondary immunization the local immunity is more manifested in comparison with the primary one.     

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.     

Combined Poly(Lactide-Co-Glycolide) Microspheres Containing Diphtheria Toxoid for a Single-shot Immunization

To develop a single-shot vaccine containing diphtheria toxoid (DT) with a sufficient immune response, poly(lactide-co-glycolide) (PLGA) microspheres were prepared by water-in-oil-in-water double emulsification and solvent extraction techniques using low or high-molecular-weight PLGA (LMW-MS or HMW-MS). Stearic acid (SA) was introduced to HMW-MS (HMW/SA-MS) as a release modulator. Mean particle sizes (dvs, μm) varied between the prepared microspheres, with LMW-MS, HMW-MS, and HMW/SA-MS having the sizes of 29.83, 110.59, and 69.5 μm, respectively; however, the protein entrapment and loading efficiency did not vary, with values of 15.2–16.8 μg/mg and 61–75%, respectively. LMW-MS showed slower initial release (~?2 weeks) but faster and higher release of antigen during weeks 3~7 than did HMW-MS. HMW/SA-MS showed rapid initial release followed by a continuous release over an extended period of time (~?12 weeks). Mixed PLGA microspheres (MIX-MS), a combination of HMW/SA-MS and LMW-MS (1:1), demonstrated a sufficient initial antigen release and a subsequent boost release in a pulsatile manner. Serum antibody levels were measured by ELISA after DT immunization of Balb/c mice, and showed a greater response to MIX-MS than to alum-adsorbed DT (control). A lethal toxin challenge test with MIX-MS (a DT dose of 18 Lf) using Balb/c mice revealed complete protection, indicating a good candidate delivery system for a single-shot immunization.     

Liposomes as adjuvant for combination vaccines

In the present study tetanus toxoid (TT) loaded liposomes and diphtheria toxoid (DT) loaded liposomes were prepared by reverse phase evaporation method and after combining these two vaccines the potential advantages were investigated. Prepared systems were characterized for the size, shape and entrapment efficiency. SDS-PAGE analysis of TT and DT was also performed. The selected liposomal formulations were administered subcutaneously to Balb/c mice and their immune responses were determined using ELISA after 15, 30, 45 days. After boosting the maximum immune response was observed after 45 days and was found to be 0.831 and 0.749 for TT loaded liposome and DT loaded liposomes respectively. When the mice were immunized subcutaneously with the physical mixture of TT loaded liposomes and DT loaded liposomes the immune response for the combination vaccine was found to be 1.44 and 0.741 for the TT and DT respectively. The result showed that the immune response of TT increased when it was combined with DT in liposomes. This confirms adjuvantcity of DT vis-a-vis immunogenicity. Thus, carrier mediated cocktail vaccination holds promise for clinical applications.