VacPertagen

Pharmacotherapeutic group: Pertussis, purified antigen, combination with toxoids. ATC code: J07AJ52 Clinical trials The immune responses observed one month after vaccination with ADACEL in 265 children, 527 adolescents and 743 adults are shown in the table below. Table 2: Immune response of children, adolescents and adults one month after vaccination with ADACEL Antibody Criteria Children (4 - 6 years) 1 (N=265) % Adolescents (11 - 17 years) 2 (N=527) % Adults (18 - 64 years) 2 (N=743) % Diphtheria (SN, IU/mL) ≥0.1 100 99.8 94.1 Tetanus (ELISA, IU/mL or EU/mL) ≥0.1 100 100 100 Pertussis (ELISA, EU/mL) PT FHA PRN FIM Booster Response 3 91.9 88.1 94.6 94.3 92.0 85.6 94.5 94.9 84.4 82.7 93.8 85.9 DTaP: diphtheria toxoid [paediatric dose], tetanus and acellular pertussis; ELISA: Enzyme Linked Immunoassay; EU: ELISA units; IU: international units; N: number of participants with available data; SN: seroneutralisation. 1 Study Td508 was conducted in Canada with children 4-6 years of age. 2 Study Td506 was conducted in the United States with adolescents 11-17 years of age and adults 18-64 years of age. 3 For children in Study Td508 who were previously primed with DTaP at 2, 4, 6 and 18 months of age, a booster response is defined as a 4-fold increase in concentration of anti-pertussis antibodies.‍‍‍‍‍‍​​​‍​​​​​​ For adolescents and adults in Study Td506, a booster response is defined as a 2-fold increase in concentration of anti-pertussis antibodies in participants with high pre-vaccination concentration and a 4-fold increase in participants with low pre-vaccination concentration. The safety and immunogenicity of ADACEL in adults and adolescents was shown to be comparable to that observed with a single dose of an adult formulation diphtheria-tetanus (Td) adsorbed vaccine containing the same amount of tetanus and diphtheria toxoids. Serological correlates for protection against pertussis have not been established. On comparison with data from the Sweden I pertussis efficacy trials conducted between 1992 and 1996, where primary immunization with Sanofi Pasteur _acellular pertussis infant DTaP formulation confirmed a protective efficacy of 85% against pertussis disease, it is considered that ADACEL had elicited protective immune responses. The pertussis antibody levels for all antigens following a booster dose of ADACEL in adolescents and adults exceeded those observed in a household contact study nested within the efficacy trial. Table 3: Ratio of pertussis antibody GMC observed one month after a dose of ADACEL in adolescents and adults compared with those observed in infants one month following vaccination at 2, 4 and 6 months of age in the Sweden I efficacy trial with DTaP (PPI Population 1 ) Adolescents (11-17 years) 2 Adults (18-64 years) 2 ADACEL/DTaP 3 GMC Ratio (95% CIs) 4 ADACEL/DTaP 3 GMC Ratio (95% CIs) 4 Participants N=524-526 N=741 Anti-PT 3.6 (2.8, 4.5) 2.1 (1.6, 2.7) Anti-FHA 5.4 (4.5, 6.5) 4.8 (3.9, 5.9) Anti-PRN 3.2 (2.5, 4.1) 3.2 (2.3, 4.4) Anti-FIM 5.3 (3.9, 7.1) 2.5 (1.8, 3.5) DTaP: diphtheria toxoid [paediatric dose], tetanus and acellular pertussis; GMC: Geometric Mean Concentration; N: number of participants with available data; PPI: per protocol immunogenicity 1 Eligible participants for whom immunogenicity data were available. 2 Study Td506 was conducted in the United States with adolescents 11-17 years of age and adults 18-64 years of age. Antibody GMCs, measured in ELISA units were calculated separately for infants, adolescents and adults. 3 N = 80, number of infants who received DTaP at 2, 4 and 6 months of age with available data post-dose 3 (sera from the Sweden I Efficacy Trial tested contemporaneously with samples from study Td506). 4 GMCs following COVAXiS were non-inferior to GMCs following DTaP (lower limit of 95% CI on the ratio of GMCs for COVAXiS divided by DTaP >0.67). Antibody persistence Serology follow-up studies were conducted at 3, 5 and 10 years, in individuals previously immunized with a single booster dose of ADACEL. Persistence of seroprotection to diphtheria and tetanus, and seropositivity to pertussis is summarised in Table 4. Table 4: Persistence of Seroprotection/Seropositivity Rates (%) in Children, Adolescents and Adults at 3-, 5- and 10- years following a dose of ADACEL (PPI Population 1 ) Children (4-6 years) 2 Adolescents (11-17 years) 3 Adults (18-64 years) 3 Time since ADACEL dose 5 years 3 years 5 years 10 years 3 years 5 years 10 years Participants N=128-150 N=300 N=204-206 N=28-39 N=292 N=237-238 N=120-136 Antibody % Seroprotection/Seropositivity Diphtheria (SN, IU/mL) ≥ 0.1 86.0 97.0 95.1 94.9 81.2 81.1 84.6 ≥ 0.01 100 100 100 100 95.2 93.7 99.3 Tetanus (ELISA, IU/mL) ≥ 0.1 97.3 100 100 100 99.0 97.1 100 Pertussis (ELISA, EU/mL) Sero-positivity 4 PT 63.3 97.3 85.4 82.1 94.2 89.1 85.8 FHA 97.3 100 99.5 100 99.3 100 100 PRN 95.3 99.7 98.5 100 98.6 97.1 99.3 FIM 98.7 98.3 99.5 100 93.5 99.6 98.5 ELISA: Enzyme Linked Immunoassay; EU: ELISA units; IU: international units; N: number of participants with available data; PPI: per protocol immunogenicity; SN: seroneutralisation; 1 Eligible participants for whom immunogenicity data were available for at least one antibody at the specified time-point. 2 Study Td508 was conducted in Canada with children 4-6 years of age. 3 Study Td506 was conducted in the United States with adolescents 11-17 years of age and adults 18-64 years of age. 4 Percentage of participants with antibodies ≥ 5 EU/mL for PT, ≥ 3 EU/mL for FHA and PRN, and ≥ 17 EU/mL for FIM for the year follow-up; ≥ 4 EU/mL for PT, PRN and FIM, and ≥ 3 EU/mL for FHA for the 5-year and 10-year follow-up. Immunogenicity in persons not previously vaccinated or with an unknown vaccination status After administration of one dose of REPEVAX (Tdap-IPV; containing the same amounts of tetanus, diphtheria and pertussis antigens as ADACEL) to 330 adults ≥40 years of age that had not received any diphtheria- and tetanus-containing vaccine in the past 20 years: • ≥95.8% of adults were seropositive (≥ 5 EU/mL) for antibodies to all vaccine-containing pertussis antigens, • 82.4% and 92.7% were seroprotected against diphtheria at a threshold ≥0.1 and ≥0.01 IU/mL, respectively, • 98.5% and 99.7% were seroprotected against tetanus at a threshold ≥0.1 and ≥0.01 IU/mL, respectively, • and ≥98.8% were seroprotected against polio (types 1, 2 and 3) at a threshold ≥1:8 dilution. After administration of two additional doses of diphtheria- tetanus- and polio-containing vaccine to 316 subjects, one and six months after the first dose, the seroprotection rates against diphtheria were 94.6% and 100% (≥0.1 and ≥ 0.01 IU/mL, respectively), against tetanus 100% (≥0.1 IU/mL), and against polio (types 1, 2 and 3) 100% (≥1:8 dilution). Immunogenicity following repeat vaccination The immunogenicity of ADACEL following repeat vaccination 10 years after a previous dose of ADACEL or REPEVAX, has been evaluated. One month post-vaccination ≥ 98.5% of study participants achieved seroprotective antibody levels (≥ 0.1 IU/ml) for diphtheria and tetanus, and ≥ 84% achieved booster responses to the pertussis antigens. (A pertussis booster response was defined as a post-vaccination antibody concentration ≥ 4 times the LLOQ if the pre-vaccination level was < LLOQ; ≥ 4 times the pre-vaccination level if that was ≥ LLOQ but < 4 times LLOQ; or ≥ 2 times the pre-vaccination level if that was ≥ 4 times the LLOQ). Based on the serology follow-up and repeat vaccination data, ADACEL can be used instead of a dT vaccine to boost immunity to pertussis in addition to diphtheria and tetanus. 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, (i.e., 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 ADACEL 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 REPEVAX 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 or REPEVAX 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 or REPEVAX and the infants' or toddlers' responses to diphtheria, tetanus, Haemophilus influenzae type b, inactivated poliovirus, or pneumococcal antigens. 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%. Table 5: Vaccine effectiveness (VE) against pertussis disease in young infants born to mothers vaccinated during pregnancy with ADACEL or REPEVAX in 3 retrospective studies. Location Vaccine VE (95% CI) VE estimation method Infant follow-up period UK REPEVAX 93% (81, 97) unmatched case-control 2 months US ADACEL* 91.4% (19.5, 99.1) cohort regression model 2 months UK REPEVAX 93% (89, 95) screening (case-coverage) 3 months * Approximately 99% of women were vaccinated with ADACEL