Pharmacology: Tetanus and Diphtheria: Tetanus is an acute and often fatal disease caused by an extremely potent neurotoxin produced by C. tetani. The toxin causes neuromuscular dysfunction, with rigidity and spasms of skeletal muscles. 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. A tetanus antitoxin level of at least 0.1 IU/mL as measured by the ELISA used in clinical studies of ADACEL is considered as protective for tetanus. Levels of 1.0 IU/mL have been associated with long-term protection.
Strains of C. diphtheriae that produce diphtheria toxin can cause severe or fatal illness characterized by membranous inflammation of the upper respiratory tract and toxin-induced damage to the myocardium and nervous system. 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. Levels of 1.0 IU/mL have been associated with long-term protection.
Pertussis: 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), the same pertussis components as in ADACEL (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 %. A household contact study that was nested in this efficacy trial demonstrated that there were statistically significant correlations between clinical protection and the presence of antibodies against PT, PRN and FIM in pre-exposure sera.
Minimum serum antibody levels to specific pertussis vaccine components that confer protection against the development of clinical pertussis have not been identified. 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. In ADACEL clinical trials, in children, adolescents and adults <65 years of age, post vaccination Geometric Mean Concentrations (GMCs) for all pertussis antibodies were consistently above those of TRIPACEL in the SWEDEN I Efficacy Trial. Older adults (≥65 years of age) vaccinated with a single dose of ADACEL achieved lower GMCs for some of the pertussis antibodies than did infants who had received 3 or 4 doses of TRIPACEL. Nevertheless, their post-immunization anti-pertussis antibody levels were 4.4- to 15.1-fold higher than pre-immunization levels, suggested an improved degree of protection against pertussis.
Duration of Effect: Long-term follow up of serum antibody levels in adolescents and adults who received a single dose of ADACEL show that protective levels for tetanus antitoxin (≥0.01 EU/mL) and diphtheria antitoxin (≥0.01 IU/mL) persist in 99.2 % and 92.6 % of participants, respectively, 10 years post-vaccination. While protective levels against pertussis have not yet been clearly defined, pertussis antibody levels remain 2 to 9 fold higher than pre-immunization levels after 5 years. However at 10 years post-vaccination pertussis antibody levels were observed to decline towards pre-vaccination levels.
Tetanus and diphtheria toxoid boosters are recommended every 10 years. The serology follow-up and redosing data for ADACEL suggests that it can be used instead of tetanus and diphtheria toxoid vaccine for boosting at 10-years intervals in adults.
Passive protection of neonates and infants against pertussis: Based on findings from multiple studies of ADACEL and ADACEL-POLIO administered to pregnant women primarily during the 2nd or 3rd 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 1.)
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