ADACEL Rx

The effectiveness of the tetanus toxoid and diphtheria toxoid used in Adacel was based on the immune response to these antigens compared to a US licensed Tetanus and Diphtheria Toxoids Adsorbed For Adult Use (Td) vaccine manufactured by Sanofi Pasteur. The effectiveness of the pertussis antigens used in Adacel was evaluated based on a comparison of pertussis antibody levels achieved in recipients of Adacel with those obtained in infants after 3 or 4 doses of Daptacel.

Study Td506

• Comparative, randomized, observer-blinded, controlled trial.
• 4480 participants: 2053 adolescents (11-17 years of age) and 2427 adults (18-64 years of age); demographics were similar within age groups and between the vaccine groups.
• Participants (N=4461) were randomly assigned to receive 1 dose of either Adacel or Td vaccine.
• Anti-tetanus and anti-diphtheria seroprotection rates (≥0.1 IU/mL) and booster response rates were comparable between Adacel and Td vaccines. 
• Adacel induced pertussis antibody levels that were noninferior to those of infants who received 3 doses of Daptacel vaccine.
• Acceptable booster responses to each of the pertussis antigens were also demonstrated.

Study NCT01311557

• Assessed the comparative immunogenicity of a first vaccination with Adacel administered to adolescents.
• Findings showed noninferiority was demonstrated for booster responses to tetanus, and diphtheria toxoids, GMCs to the pertussis antigens and booster responses to the pertussis antigens (PT, FHA, PRN).
• For FIM, noninferiority was not demonstrated.

Study NCT01439165

• Individuals 18 to 64 years of age who had received a dose of Adacel 8-12 years previously were randomly assigned to receive a second dose of Adacel or Td vaccine.
• Booster response rates to tetanus toxoid and diphtheria toxoid following a second vaccination with Adacel: 74.5% and 83.2%, respectively.
• Booster response rates to tetanus toxoid and diphtheria toxoid following a second vaccination with Td vaccine: 81.6% and 84.1%, respectively.
• Booster response rates for PT and FHA were noninferior in Adacel participants compared with pre-specified criteria for booster response rates, but noninferiority was not achieved for PRN and FIM booster response rates.

Study in Pregnant Women

Approval was based on a re-analysis of data from an observational study of Tdap vaccine effectiveness in the US (ClinicalTrials.gov Identifier: NCT05040802). Adacel was estimated to be 88% (95% CI, 43.8-97.4) effective in preventing pertussis in infants younger than 2 months when administered during the third trimester of pregnancy and at least 14 days before delivery based on data from 101 cases of pertussis in infants younger than 2 months of age (including 5 infants whose mothers received Adacel during the third trimester and ≥14 days before delivery) and 171 controls (including 27 infants whose mothers received Adacel during the third trimester and ≥14 days before delivery).

Published studies have reported diminished immune responses to pertussis antigens in DTaP-containing vaccines administered to infants whose mothers received Adacel during the third trimester of pregnancy compared with infants whose mothers did not receive Adacel during the third trimester of pregnancy. It is unclear whether these diminished immune responses resulted in diminished effectiveness of pertussis vaccination in infants.

Concomitant Hepatitis B Vaccine Administration

• Evaluated in an open-label, randomized controlled study; 410 adolescents enrolled.
• One group received Adacel and Hep B vaccines concurrently (n=206), while the other (n=204) received Adacel at the first visit, then 4-6 weeks later received Hep B vaccine.
• The second dose of Hep B vaccine was given 4-6 weeks after the first dose.
• No interference was observed in the immune responses to any of the vaccine antigens when Adacel and Hep B vaccine were given concurrently or separately.

Concomitant Trivalent Inactivated Influenza Vaccine (TIV; Fluzone) Administration

• Evaluated in an open-label, randomized, controlled study conducted in 720 adults, 19-64 years of age. 
• In one group, participants received Adacel and TIV vaccines concurrently (n=359), while the other group received TIV at the first visit, then 4-6 weeks later received Adacel (n=361). 
• Immune responses were comparable for concurrent and separate administration for diphtheria, tetanus, pertussis antigens, and influenza antigens. 
• Tetanus booster response rates were significantly lower in the group receiving the vaccines concurrently vs separately; however, greater than 98% of participants in both groups achieved seroprotective levels.