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Development of a mouse model to estimate the potency of the diphtheria toxoid component of diphtheria-tetanus and diphtheria-tetanus-pertussis vaccines.

A mouse model to estimate the potency of the diphtheria toxoid component in diphtheria-tetanus vaccines and diphtheria-tetanus-pertussis vaccines has been developed as an alternative to the conventional method of testing in guinea-pigs. Optimal conditions with regard to dose, route and period of immunization have been standardized. The maximum levels of antitoxin were detected five weeks after vaccination and the s.c. route was found to be optimal. Potency data have been compared with other studies in mouse models and with those obtained by the conventional method in guinea-pigs.

Animals↗

Protection against group A streptococcus by immunization with J8-diphtheria toxoid: contribution of J8- and diphtheria toxoid-specific antibodies to protection.

A conformationally constrained, minimally conserved peptide from the M protein of group A streptococcus (GAS) has been defined. It consists of 12 amino acids from the C-repeat region within a non-M protein helix-forming sequence and is referred to as "J8." Here, we investigate the immunogenicity of a J8-diphtheria toxoid (DT) conjugate adjuvanted with the human-compatible adjuvants, SBAS2 and alum, and demonstrate that it is capable of inducing opsonic antibodies and can protect outbred mice from virulent challenge. In a range of experiments, protection correlated with the titer of J8-specific antibodies and not with the induction of J8-specific T cells. However, DT-specific antibodies (as well as J8-specific antibodies) were shown to stain the surface of fixed GAS and to be capable of opsonizing live organisms. DT may be an ideal carrier protein for J8 and other GAS peptides for GAS vaccines.

Adjuvants, Immunologic↗

Controlled trial of Haemophilus influenzae type B diphtheria toxoid conjugate combined with diphtheria, tetanus and pertussis vaccines, in 18-month-old children, including comparison of arm versus thigh injection.

A randomized, controlled comparison was made in 175 healthy 18-month-old children given either diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) and haemophilus b diphtheria toxoid conjugate vaccine (PRP/D) concurrently at separate sites (66 children) or a new vaccine combining these products (109 children). Rates of local or systemic adverse effects postimmunization and antibody responses to each component did not differ significantly between groups. DTP-containing vaccines were better tolerated when given in the thigh than in the arm. The combination DTP-PRP/D vaccine performed satisfactorily at 18 months of age, avoiding the inconvenience of two injections.

Arm↗

Comparison of the morbidity of tetanus toxoid boosters with tetanus-diphtheria toxoid boosters.

A double-blind randomized trial was performed to compare the subjective morbidity of tetanus toxoid (T) with that of tetanus-diphtheria toxoid (Td). Symptoms occurred in 46 (48%) of 93 patients who received T, and in 75 of 100 patients who received Td (chi 2 = 12.3; P less than .001). The effectiveness of immunization is clear, but with shift from use of T to Td as recommended, adherence to immunization guidelines and taking of adequate immunization histories becomes even more important.

Adult↗

Effect of different concentrations of diphtheria toxoid & aluminum phosphate on potency of diphtheria component in DPT vaccines.

An effort was made to determine the optimum concentration of diphtheria toxoid in combination with aluminum phosphate gel in DPT vaccines which may give a safe, potent and economical preparation. The effect of four different concentrations of aluminum phosphate and three different antigenic concentrations of diphtheria toxoid on potency of diphtheria component in DPT vaccine was assessed. A gradual increase in potency was seen with increase in toxoid concentration and a gradual decrease in potency with the increase in aluminum phosphate content. Vaccines made with minimum quantities of toxoid (30 Lf/ml) and aluminum phosphate (3 mg/ml) were found to be highly satisfactory. Vaccines prepared with high antigenic purity toxoid have better potency, as compared to those prepared with a relatively low antigenic purity toxoid.

Adjuvants, Immunologic↗

Simultaneous administration of Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine with routine diphtheria-tetanus-pertussis and inactivated poliovirus vaccinations of childhood.

A Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) is capable of protecting infants against invasive H. influenzae diseases. Therefore it is very likely that it will be incorporated in routine vaccination schedules during the next few years. In order to test the suitability of simultaneous administration of PRP-D and other vaccines we administered it to 25 infants mixed with diphtheria-tetanus-pertussis vaccine at 3, 4 and 6 months and simultaneously, but in a separate syringe, with inactivated polio vaccine at 12 months. A comparison group of equal size received only diphtheria-tetanus-pertussis and inactivated poliovirus vaccines. The concentration of postvaccination antibodies to diphtheria toxoid was 0.411 IU/ml in the group that received PRP-D vs. 0.352 IU/ml in the comparison group, to tetanus toxoid 3.666 vs. 3.668 IU/ml and the neutralization titer to poliovirus type 1 was 370 vs. 320 units in the comparison group, to type 2 titer values were 230 vs. 270 units and to type 3, respectively, 210 vs. 290 units. Thus the seroresponse to antigens in routine vaccines was not affected by the presence of PRP-D in the vaccination schedule, and PRP-D can safely and effectively be included in the vaccination schedule of infancy.

Bacterial Vaccines↗

Immune status and booster effects of low doses of diphtheria toxoid in Swedish medical personnel.

During a diphtheria outbreak among Swedish alcoholics in 1984-1985, only 60% of 328 medical staff at risk for exposure had diphtheria antitoxin titers greater than or equal to 0.01 IU/ml, which is usually considered to give relative protection. 21% had levels between 0.01-0.09 IU/ml and the remaining 39% had titers greater than or equal to 0.1 IU/ml. Booster doses of 0.5 Lf-12.5 Lf of diphtheria toxoid were given to 450 vaccinees. Of 72 individuals with low pre-immunization titers, who were immunized with less than or equal to 2.5 Lf diphtheria toxoid, 40% failed to reach greater than or equal to 0.1 IU/ml when analyzed 4 weeks after vaccination. Local tenderness and swelling greater than 5 cm at the site of injection or general discomfort was found in 11% of those immunized with low dose diphtheria toxoid (less than or equal to 2.5 Lf). When the dose 0.5 Lf of diphtheria toxoid was combined with tetanus toxoid (3.75 Lf) the frequency of adverse reactions increased to 34% (p less than 0.001). The study shows that vaccination status in medical personnel must also be continuously examined in countries where diphtheria is rare and that low booster doses of diphtheria toxoid may not achieve an adequate immune response.

Adolescent↗

Immunogenicity of tetanus-diphtheria toxoids (Td) among Ukrainian adults: implications for diphtheria control in the Newly Independent States of the Former Soviet Union.

After 30 years of control, epidemic diphtheria returned to the Soviet Union in 1990. To develop control strategies, the immunogenicity of the tetanus and diphtheria toxoids (Td) vaccine was assessed. Workers who were 18-67 years old received two Td immunizations separated by 30 days. A neutralization assay determined diphtheria antitoxin (DAT) on enrollment and on days 7, 30, 60, and 425. On enrollment, 43.0% of 488 workers had DAT <0.1 IU/mL. After one dose, 88.5% had DAT >/=0.1 IU/mL, after two doses, 92.2% had >/=0.1 IU/mL and >90% of participants <30 or >/=50 years of age attained >/=1.0 IU/mL; however, only 78.4% of those who were 30-39 years old and 51.8% of those who were 40-49 years old achieved >/=1.0 IU/mL after two doses. To control the epidemic in Ukraine, one Td dose should be administered to virtually the entire population (persons 30-49 years old require three doses of Td for optimal individual protection and to maximize population immunity).

Adolescent↗

Collagen minipellet as a controlled release delivery system for tetanus and diphtheria toxoid.

The use of biodegradable polymer matrices as a single-dose vaccine delivery system was investigated using tetanus toxoid (TT) and diphtheria toxoid (DT). BALB/c mice were immunized with TT or DT in different formulations including individual, in minipellet and aluminum hydroxide (alum), and the antibody responses were monitored for 48 weeks. Antigens entrapped in minipellet elicited higher antibody responses compared to those obtained with individual antigens and antigens adsorbed to alum and the antibody levels remained elevated over 48 weeks. In addition, minipellet formulations induced the same subclasses of antibodies induced by alum formulations. These results raise the possibility to obtain optimal and long-lasting immune responses by a single administration of minipellet formulations.

Adjuvants, Immunologic↗