Pharmacology: Tetanus and Diphtheria:
Protection against disease attributable to C. tetani
is due to the development of neutralizing antibodies to tetanus toxin. A serum tetanus antitoxin level of at least 0.01 IU/mL, measured by neutralization assay, is considered the minimum protective level. One month after a single booster dose of ADACEL-POLIO, seroprotective tetanus antitoxin levels were achieved in 100% of adults and adolescents, and at least 100% of children 3.5 to 4.1 years of age.
Protection against disease attributable to C. diphtheriae
is due to the development of neutralizing antibodies to diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL is the lowest level giving some degree of protection. Antitoxin levels of at least 0.1 IU/mL are generally regarded as protective for diphtheria. 83.8% of adults, 97.1% of adolescents and at least 97.6% of children 3.5 to 4.1 years of age achieved a seroprotective antitoxin level of 0.1 IU/mL against diphtheria.
Pertussis (whooping cough) is a respiratory disease caused by B. pertussis
. This Gram-negative coccobacillus produces a variety of biologically active components, though their role in either the pathogenesis of, or immunity to, pertussis has not been clearly defined. The mechanism of protection from B. pertussis
disease is not well understood. However, in a clinical trial in Sweden (Sweden I Efficacy Trial) using TRIPACEL [Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed], the same pertussis components as present in ADACEL-POLIO (i.e., PT, FHA, PRN and FIM) have been shown to prevent pertussis in infants with a protective efficacy of 85.2% using the World Health Organization (WHO) case definition (≥21 consecutive days of paroxysmal cough with culture or serologic confirmation or epidemiological link to a confirmed case). In the same study, the protective efficacy against mild disease was 77.9%.
Minimum serum antibody levels to specific pertussis vaccine components that confer protection against the development of clinical pertussis have not been established. Nevertheless, a number of studies have demonstrated a correlation between the presence of serum antibody responses to pertussis vaccine components and protection against clinical disease. The acellular pertussis formulations of ADACEL-POLIO and ADACEL compared to TRIPACEL differ only in the amount of PT (2.5 μg in ADACEL-POLIO and ADACEL versus 10 μg in TRIPACEL) and the amount of diphtheria toxoid (2 Lf in ADACEL-POLIO and ADACEL versus 15 Lf in TRIPACEL). Furthermore, the IPV antigens present in ADACEL-POLIO are not included in the formulation of TRIPACEL.
The efficacy of ADACEL-POLIO is based on a comparison of pertussis antibody levels achieved in ADACEL-POLIO recipients with those measured with TRIPACEL in the Sweden I Efficacy Trial. In particular, ADACEL-POLIO was demonstrated, both in children and in adolescents and adults, to elicit antibody levels against pertussis antigens, which were consistently higher that those found to be protective in the Sweden I Efficacy Trial. In addition, in a clinical study with ADACEL among Canadian 4 to 6 year-olds, it was demonstrated that, in the context of the Canadian immunization schedule, the pertussis antigens formulation of ADACEL-POLIO also elicited serum antibody levels that were consistently higher than those measured in the Sweden I Efficacy Trial.
Inactivated poliomyelitis vaccine induces the production of detectable levels of neutralizing antibodies against each type of poliovirus. The detection of type-specific neutralizing antibodies has been correlated with protection. In all clinical trials, 99.0% to 100% of vaccinees in all age groups achieved seroprotective levels (≥1:8 dilution) of anti-poliovirus antibodies for all three types.
Duration of Effect:
Long-term follow-up of serum antibody levels in adolescents and adults who received a single dose of ADACEL-POLIO shows that protective levels for tetanus antitoxin (≥0.01 IU/mL) and diphtheria antitoxin (≥0.01 IU/mL) persist in 100% and at least 79.2% of participants, respectively, after at least 5 years. Protective levels of anti-poliovirus antibodies (≥1:8) persist in 98.2% to 100.0% of both adolescents and adults after 5 years. While protective levels against pertussis have not yet been clearly defined, pertussis antibody levels remain several-fold higher than pre-immunization levels after 5 years.
Long-term follow-up of serum antibody levels in children who received a single dose of ADACEL-POLIO at 3.5 to 5 years of age shows that protective levels for tetanus antitoxin (≥0.01 IU/mL) and diphtheria antitoxin (≥0.01 IU/mL) persist in 100.0% of participants, 3 years after immunization. Protective levels of anti-poliovirus antibodies (≥1:8) persist in 97.9 to 100.0% of participants after 3 years. While protective levels against pertussis have not yet been clearly defined, after 3 years, pertussis antibody levels remain higher than pre-immunization levels. (25)
According to NACI, tetanus and diphtheria toxoid boosters are recommended every 10 years, however, the optimal interval for administering subsequent booster doses with ADACEL-POLIO has not been determined. Nevertheless, a clinical study conducted with ADACEL demonstrated that the incidence and severity of adverse events reported after administration of ADACEL as early as 2 years after the last dose of tetanus and diphtheria vaccine were similar to those observed after administration at greater time intervals, up to 10 years.
Passive protection of neonates and infants against pertussis: Based on findings from multiple studies of ADACEL-POLIO and ADACEL administered to pregnant women primarily during the 2nd
trimester of gestation: Pertussis antibody responses in pregnant women are generally similar to those in non-pregnant women.
Maternal antibody directed against pertussis antigens persists for 2 to 4 months after birth and may be associated with blunting of the infant immune response to active immunization against pertussis (see PRECAUTIONS).
The effectiveness of maternal immunization against pertussis in the first 3 months of life has been estimated to be >90%. (See Table 3.)
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