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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.
In a clinical study, individuals 65 years of age and older received a single dose of Adacel vaccine. Based on pre-specified criteria, persons 65 years of age and older who received a dose of Adacel vaccine had lower geometric mean concentrations of antibodies to PT, PRN and FIM when compared to infants who had received a primary series of TRIPACEL, Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP). Nevertheless, their post-immunization anti-pertussis antibody levels were 4.4-15.1-fold higher than pre-immunization levels.
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-year intervals in adults.
Immunogenicity: Immunogenicity in pregnant women: Pertussis antibody responses in pregnant women are generally similar to those in non-pregnant women. Vaccination during the second or third trimester of pregnancy is optimal for antibody transfer to the developing fetus.
Immunogenicity against pertussis in infants (<3 months of age) born to women vaccinated during pregnancy: Data from 2 published randomized controlled trials demonstrate higher pertussis antibody concentrations at birth and at 2 months of age, (ie, prior to the start of their primary vaccinations) in infants of women vaccinated with ADACEL during pregnancy compared with infants of women not vaccinated against pertussis during pregnancy.
In the first study, 33 pregnant women received ADACEL and 15 received saline placebo at 30 to 32 weeks gestation. The geometric mean concentrations (GMC) in EU/mL for the anti-pertussis antibodies to the PT, FHA, PRN, and FIM antigens in infants of vaccinated women were, respectively, 68.8, 234.2, 226.8, and 1867.0 at birth, and 20.6, 99.1, 75.7, and 510.4 at 2 months of age. In the control-group infants, the corresponding GMCs were 14.0, 25.1, 14.4, and 48.5 at birth, and 5.3, 6.6, 5.2, and 12.0 at 2 months. The GMC ratios (ADACEL/control group) were 4.9, 9.3, 15.8, and 38.5 at birth, and 3.9, 15.0, 14.6, and 42.5 at 2 months.
In the second study, 134 pregnant women received Tdap and 138 received a tetanus and diphtheria control vaccine at a mean gestational age of 34.5 weeks. The GMCs (EU/mL) for the anti-pertussis antibodies to the PT, FHA, PRN, and FIM antigens in infants of vaccinated women were, respectively, 54.2, 184.2, 294.1, and 939.6 at birth, and 14.1, 51.0, 76.8, and 220.0 at 2 months of age. In the control-group infants, the corresponding GMCs were 9.5, 21.4, 11.2, and 31.5 at birth, and 3.6, 6.1, 4.4, and 9.0 at 2 months. The GMC ratios (ADACEL/control group) were 5.7, 8.6, 26.3, and 29.8 at birth, and 3.9, 8.4, 17.5, and 24.4 at 2 months.
These higher antibody concentrations should provide passive immunity against pertussis for the infant during the first 2 to 3 months of life, as has been shown by observational effectiveness studies.
Immunogenicity in infants and toddlers born to women vaccinated during pregnancy: For infants of women vaccinated with ADACEL or ADACEL-POLIO during pregnancy, the immunogenicity of routine infant vaccination was assessed in several published studies. Data on the infant response to pertussis and non-pertussis antigens were evaluated during the first year of life.
Maternal antibodies derived after ADACEL and ADACEL-POLIO vaccination in pregnancy may be associated with blunting of the infant immune response to active immunization against pertussis. Based on current epidemiological studies, this blunting may not have clinical relevance.
Data from several studies did not show any clinically relevant blunting from vaccination in pregnancy with ADACEL and ADACEL-POLIO and the infants' or toddlers' responses to diphtheria, tetanus, Haemophilus influenzae type b, inactivated poliovirus, or pneumococcal antigens.
Effectiveness: Effectiveness against pertussis in infants born to women vaccinated during pregnancy: The vaccine effectiveness in the first 2-3 months of life for infants born to women vaccinated against pertussis during the third trimester of pregnancy has been evaluated in 3 observational studies. The overall effectiveness is >90%. (See Table 1.)
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