BOOSTRIX Rx

Effectiveness of Boostrix, Infanrix, and Pediarix

Effectiveness of Boostrix

• The effectiveness of the tetanus and diphtheria toxoid components of Boostrix is based on the immunogenicity of the individual antigens compared with US-licensed vaccines using established serologic correlates of protection. 

• The effectiveness of the pertussis components of Boostrix was evaluated by comparison of the immune response of adolescents and adults following an initial dose of Boostrix to the immune response of infants following a 3-dose primary series of Infanrix or by comparison of the immune response of adults following an additional dose of Boostrix to the immune response of infants following a 3-dose primary series of Pediarix. In addition, the ability of Boostrix to induce a booster response to each of the antigens was evaluated.

Immune Responses to Pertussis Antigens of Boostrix Compared with Infanrix or Pediarix

• Although a serologic correlate of protection for pertussis has not been established, serological data from a subset of infants immunized with a 3-dose primary series of Infanrix in the German household contact study were compared with the sera of adolescents and adults immunized with an initial dose of Boostrix.

• Serological data from infants immunized with a 3-dose primary series of Pediarix in an additional pediatric study were compared with the sera of adults immunized with an additional dose of Boostrix.

• The majority of subjects in the study of Infanrix had only anti-PT (pertussin toxin) serology data.

Immunological Evaluation following an Initial Dose of Boostrix

Adolescents (Aged 10 to 18 years)

• In a multicenter, randomized, observer-blinded, controlled US study, the immune responses to each of the antigens in Boostrix were evaluated in sera obtained approximately 1 month after administration of a single dose of vaccine to adolescent subjects (aged 10 to 18 years).

• 98% of participants received the recommended series of 4 or 5 doses of either DTwP or a combination of DTwP and DTaP in childhood.

• Boostrix and the comparator Td vaccine had comparable anti-tetanus and anti-diphtheria seroprotective rates ((≥0.1 IU/mL by ELISA) and booster response rates 1 month after a single dose.

• Response to Pertussis Antigens:

• One month after a single dose of Boostrix in adolescents: anti-PT, anti-FHA, and anti-PRN antibody concentrations were noninferior to those infants after a primary vaccinations series with Infanrix.

Adults (Aged 19 to 64 Years)

• The multicenter, randomized, observer-blinded US study compared the immunogenicity of Boostrix to the licensed comparator Tdap vaccine (Sanofi Pasteur). Patients who did not receive a tetanus-diphtheria booster within 5 years were given a single dose of the vaccines. 

• The immune responses to each of the antigens in Boostrix were evaluated in sera obtained approximately 1 month after administration.

• Response to Tetanus and Diphtheria Toxoids:

• The anti-tetanus and anti-diphtheria seroprotective rates (≥0.1 IU/mL by ELISA) were comparable between Boostrix and the comparator Tdap vaccine 1 month after a single dose.

• Response to Pertussis Antigens:

• The PT antigen booster response lower limit of the 95% CI (74.9%) for Boostrix did not exceed the pre-defined limit of 80%.

• The GMCs to each of the pertussis antigens 1 month following a single dose of Boostrix were compared with the GMCs of a subset of infants following a 3-dose primary series of Infanrix in the German household contact study. Anti-PT, anti-FHA, and anti-PRN antibody concentrations observed in adults 1 month after a single dose of Boostrix were non-inferior to those infants following a primary vaccination series with Infanrix.

Elderly (Aged 65 Years and Older)

• In a randomized, observer-blinded US study, the immunogenicity of Boostrix was compared to a US-licensed comparator TD vaccine in elderly patients 65 years of age and older. Patients who did not receive a tetanus-diphtheria booster within 5 years were given a single dose of the vaccines.

• The immune responses to each of the antigens contained in Boostrix were evaluated in sera obtained approximately 1 month after administration.

• Response to Tetanus and Diphtheria Toxoids:

• The anti-tetanus and anti-diphtheria seroprotective rates (≥0.1 IU/mL by ELISA) were comparable between Boostrix and the comparator Tdap vaccine 1 month after a single dose.

• Response to Pertussis Antigens:

• The PT antigen booster response lower limit of the 95% CI (74.9%) for Boostrix did not exceed the pre-defined limit of 80%.

• The GMCs to each of the pertussis antigens 1 month following a single dose of Boostrix were compared with the GMCs of a subset of infants following a 3-dose primary series of Infanrix in the German household contact study. Anti-PT, anti-FHA, and anti-PRN antibody concentrations observed in the elderly 1 month after a single dose of Boostrix were non-inferior to those infants following a primary vaccination series with Infanrix.

Study in Pregnant Women

• In a re-analysis within a Bayesian meta-analysis framework of the BOOSTRIX-relevant data from an observational case-control study of Tdap vaccine effectiveness, the efficacy of Boostrix was evaluated during the third trimester of pregnancy to prevent pertussis in infants younger than 2 months of age.

• The preliminary vaccine efficacy estimate for Boostrix was 78% (95% CI, -38.0, 96.5) during the third trimester of pregnancy. This preliminary effectiveness estimate was updated using a Bayesian meta-analysis with an informative prior constructed from four observational studies that provided estimates of the vaccine effectiveness of the non-U.S. formulation of Boostrix against pertussis in infants whose mothers were immunized during pregnancy.

• To account for potential publication bias, this informative prior was downweighted by combining it with an uninformative prior. When the informative prior has 20% weight, the vaccine efficacy estimate was 81.5% (95% credible interval: 12.9, 94.5) during the third trimester of pregnancy. When the informative prior has 90% weight, the vaccine efficacy estimate was 83.4% (95% credible interval: 12.9, 94.5) during the third trimester of pregnancy.

Immune Responses to Vaccination in Infants Born to Mothers Who Received Boostrix During Pregnancy 

• In infants whose mothers received Boostrix (non-US formulation) during the third trimester of pregnancy, antibody responses to a non-US licensed DTaP-containing vaccine were diminished for anti-PT, anti-FHA and anti-PRN following the primary series (NCT 02422264), and for anti-PT and anti-FHA following a booster dose (NCT 02853929) compared to infants who received the same vaccine but whose mothers received placebo during pregnancy.

• It is not known whether the diminished immune response observed in vaccinated infants whose mothers received Boostrix (non-US formulation) during pregnancy result in diminished efficacy of pertussis vaccination in infants.

Immunological Evaluation following Revaccination with Boostrix

• The multicenter, open-label, controlled US study evaluated the immunogenicity of Boostrix in adults 20 to 29 years of age who received an initial dose of Boostrix or the comparator Td vaccine (MassBiologics) in the US adolescent (10 to 18 years of age) study (NCT01738477). All patients received Boostrix 10 years after the initial vaccination. 

• The immune responses to each of the antigens contained in Boostrix were evaluated in sera obtained approximately 1 month after vaccine administration.

• Response to Tetanus and Diphtheria Toxoids:

• The anti-tetanus and anti-diphtheria seroprotective rates (≥0.1 IU/mL by ELISA) were comparable between Boostrix and the comparator Td vaccine 1 month after a single dose.

• Response to Pertussis Antigens:

• The GMCs to each of the pertussis antigens 1 month following revaccination of Boostrix were compared with the GMCs of infants following a 3-dose primary series of Pediarix. Anti-PT, anti-FHA, and anti-PRN antibody concentrations observed in the adults 1 month after revaccination of Boostrix were noninferior to those infants following a primary vaccination series with Pediarix.

Adults (Aged 28 to 73 Years)

• The multicenter, open-label, controlled US study evaluated the immunogenicity of Boostrix in adults 28 to 73 years of age who received an initial dose of Boostrix or the license comparator Tdap vaccine (Sanofi Pasteur) in the US adult (19 to 64 years of age) study (NCT00489970). All patients received Boostrix 9 years after initial vaccination.

• The immune responses to each of the antigens contained in Boostrix were evaluated in sera obtained approximately 1 month after vaccine administration.

• Response to Tetanus and Diphtheria Toxoids:

• The anti-tetanus and anti-diphtheria seroprotective rates (≥0.1 IU/mL by ELISA) were comparable between Boostrix and the comparator Tdap vaccine 1 month after a single dose.

• Response to Pertussis Antigens: 

• The GMCs to each of the pertussis antigens 1 month following a dose of Boostrix in patients who received an initial dose of Boostrix or the licensed comparator Tdap vaccine (Sanofi Pasteur) 9 years earlier were compared with the GMCs of infants following a 3-dose primary series of Pediarix. Anti-PT, anti-FHA, and anti-PRN antibody concentrations observed in the adults 1 month after revaccination of Boostrix were noninferior to those infants following a primary vaccination series with Pediarix.

Concomitant Administration with Meningococcal Conjugate Vaccine

• A randomized study evaluated the concomitant use of Boostrix and a tetravalent meningococcal (groups A, C, Y, and W-135) conjugate vaccine (Sanofi Pasteur) in 1341 healthy adolescents aged 11 to 18 years (NCT00282295). 

• Patients were randomly assigned 1:1:1 to receive Boostrix concomitantly with meningococcal conjugate vaccine at different injection sites (n=446), Boostrix followed by meningococcal conjugate vaccine 1 month later (n=446), and meningococcal conjugate vaccine followed by Boostrix 1 month later (n=449). 

• Immune responses to diphtheria and tetanus toxoids (% of subjects with anti-tetanus and antidiphtheria antibodies ≥1.0 IU/mL by ELISA), pertussis antigens (booster responses and GMCs), and meningococcal antigens (vaccine responses) were measured 1 month (range: 30 to 48 days) after concomitant or separate administration of Boostrix and meningococcal conjugate vaccine. 

• Noninferiority for all antigens (with the exception of the anti-PRN CMC) was demonstrated for Boostrix given concomitantly with meningococcal conjugate vaccine vs with Boostrix given first. Noninferiority was demonstrated for the anti-PRN booster response.

Concomitant Administration with Fluarix (Inactivated Influenza Vaccine)

• In a multicenter, open-label, randomized, controlled study (NCT00385255), the concomitant use of Boostrix and Fluarix was evaluated in 1497 adults 19 to 64 years of age. Patients received either Boostrix concomitantly with Fluarix or Fluarix first followed by Boostrix 1 month later.

• Sera was obtained prior to and 1 month following concomitant or separate administration of Boostrix and/or Fluarix , as well as 1 month after the separate administration of Fluarix.

• Noninferiority was demonstrated for immune responses following concurrent administration of Boostrix and Fluarix to separate administration for diphtheria, tetanus, PT antigen, and influenza antigens. 

• Noninferiority was not met for the anti-pertussis antigens FHA and PRN.