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.     

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.     

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.     

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.     

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.     

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.     

Variants in the immune response to revaccination with diphtheria anatoxin in adults

The immunological effectiveness of the revaccination (made in two injections) of 488 adults aged 18-67 years with diphtheria-tetanus toxoid is discussed; the parallel study of the results of this revaccination was carried out in the diphtheria toxin neutralization test on Vero cells and in the passive hemagglutination (PHA) test. The specific features of the dynamics of the increase of diphtheria antitoxic antibodies, depending on the initial immunity level, the age and the sex of revaccinated persons, were determined. Among persons with the low level of circulating antibodies before revaccination four variants of immune response to the injection of diphtheria toxoid were registered: variant 1--rapid reaction like in secondary immune response (53.6%); variant 2--delayed but effective reaction like in primary immune response (27.3%); variant 3--slow weak response (6.5%); and variant 4--the absence of effective immune response to immunization made in 2-3 injections (12.6%). The immunological and neutralizing properties of diphtheria antitoxic antibodies in the process of immunization made in 2 injections were evaluated. Persons with abnormal immune response (variants 3 and 4) produced defective antibodies, displaying immunological activity in the PHA test, but in most cases unable to neutralize diphtheria toxin in vitro when tested on Vero cells.     

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.     

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 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.     

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.     

The immunological efficacy of one, two and three inoculations against diphtheria in adults

The outbreak of diphtheria in the Republic of Belarus developed in the presence of a sharp deficiency of immunity among the population aged 35 years and over. In connection with a higher initial immunity level resulting from vaccination made in one injection the minimum antibody level (> or = 0.01 I.U./ml) was found in 79.7% of the examinees among the population under 35 years. For the age group of 35-60 years vaccination in one and two injections proved to be insufficiently effective (the minimum protective antibody titer was found, respectively, in 64.3% and 63.3% of the vaccinees). To achieve the full protection of this group of the population, vaccination in three injections was necessary; after that the minimum protective antibody titer was found in 90.7%, the protective antibody titer (0.1 I.U./ml) was found in 53.5% and the highly protective antibody titer (1.0 I.U./ml) was found in 11.6% of the examinees. The low level of highly protected persons among vaccinees receiving three injections was due to a low dose of diphtheria toxoid (2 Lf) in adsorbed DT-m vaccine with reduced antigen content.     

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.     

Transfer Agent of Immunity

An immune ribonucleic acid (RNA) preparation was extracted with phenol from the spleens of guinea pigs immunized with diphtheria toxoid. Antibody-carrying cells were detected by immunocyte adhesion as rosette-forming cells. When germ-free rats, conventional guinea pigs or mice were injected intraperitoneally with this preparation, the rosette-formers were detected in either peritoneal exudate cells or spleen cells, whereas serum antibodies were unable to be detected thus far in such animals. Two injections with this preparation did not cause any remarkable increase in the number of rosette-formers, and serum antibody was also not detectable. By contrast, a high titer of serum antibody was demonstrated and the number of rosette-formers increased shortly after an injection of a small amount of diphtheria toxoid into guinea pigs which had previously received an injection with immune RNA. This reaction indicates a secondary response of antibody formation. However, secondary responses were not induced by injections of immune RNA preparations in guinea pigs primed with either diphtheria toxoid or immune RNA preparation. These facts suggest that immune RNA preparations did not contain antigens or fragments thereof and the immune response induced by RNA preparation is not the same as that induced by stimulation by the antigen itself. These results moreover can be accounted for by the notion that the immune RNA preparation is able to induce “memory” cells capable of responding to a secondary stimulus with an antigen and producing a high titer of serum antibody.     

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.     

The immunization of children with combined diphtheria and tetanus vaccine in Sweden

Two groups derived from 97 children three-four months of age were vaccinated with diphtheria and tetanus vaccines containing either a routinely prepared diphtheria toxoid or a more purified preparation. Two injections were given with an interval of one month and a third injection was given one year after the first. Prior to the third injection no child was without protection against diphtheria, i.e. had an antitoxin titre less than 0.01 IU ml-1. After the third injection 95 and 94% of the children vaccinated with the routinely and more purified diphtheria toxoids, respectively, had diphtheria antitoxin titres greater than 1 IU ml-1 (estimated to provide protection for at least ten years). Systemic reactions such as fever and malaise occurred in five children. Local reactions greater than 10 cm were observed in three children and reactions greater than 5 but less than or equal to 10 cm were seen in 14% of the children. The routinely prepared combined diphtheria and tetanus vaccine, DT, produced very good immunity against diphtheria with moderate side effects. The use of a more purified diphtheria toxoid in the combined vaccine produced the same immunity and side effects.     

Simultaneous Immunization with B.C.G., Diphtheria-tetanus,and Oral Poliomyelitis Vaccines in Children Aged 13-14

The simultaneous administration of B.C.G. vaccine, diphtheria-tetanus toxoid aluminium hydroxide adsorbed vaccine, and oral poliovaccine was studied in 628 children aged 13-14 years between 1966 and 1969 in Newham, London. The efficacy of these vaccines was unaffected by administering them at the same time; routine simultaneous administration is considered justified when organizational difficulties prevent the attainment of high immunization rates with the vaccines given separately. No adverse reactions to B.C.G. or oral poliomyelitis vaccines took place, but 8% of children had moderately severe local reactions after diphtheria-tetanus aluminium hydroxide adsorbed vaccine, which were attributed to diphtheria toxoid.Serological studies showed the need for immunization against diphtheria, tetanus, and poliomyelitis at 13-14 years of age. Because of the adverse reactions to diphtheria toxoid, however, simultaneous administration of tetanus toxoid aluminium hydroxide adsorbed, oral poliomyelitis, and B.C.G. vaccines only is recommended at present.An “adult type” diphtheria-tetanus toxoid might overcome the problem of reactions, though in two to three years'' time most children aged 13-14 years will have received diphtheria-tetanus-pertussis vaccine in infancy and reinforcement might then be accomplished by a small intradermal dose of the currently available fluid diphtheria-tetanus vaccine.Continued serological studies of diphtheria and tetanus antitoxins and polio antibody are necessary to determine the future need for reinforcement of immunity; such studies should become an essential part of the surveillance of the community immunization programme.     

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.