Tdap Vaccine Clinical Trial Safety Testing Data

How was the Tdap booster vaccine tested for safety before approval? This page documents the pre-licensure clinical trial data for Boostrix and Adacel — including trial design, controls, and adverse events.

Clinical trial data for the two Tdap vaccines licensed for adolescents and adults in the US. Both Adacel (Sanofi) and Boostrix (GSK) were licensed in 2005 and both used Decavac (a Td vaccine, Sanofi) as their control. Decavac was not itself licensed via a placebo-controlled trial. Adacel contains dramatically less antigen than the infant DTaP formulation — 12.5× less diphtheria toxoid and 10× less pertussis toxin than Infanrix — because the full DTaP dose is too reactogenic in older recipients.


Adacel (Sanofi)

FieldValue
Licensed2005
Trial populationNot specified in source
Control groupDecavac (Td vaccine, Sanofi) — not licensed on placebo trial
Antigen vs. Infanrix DTaP12.5× less diphtheria toxoid; 10× less pertussis toxin

Source: FDA-approved package insert; Sanofi licensure submission.

Reduced Antigen Formulation Rationale

The dramatic reduction in antigen content was dictated by adverse reaction rates: the full DTaP antigen load used in infants causes too many adverse reactions in adolescents and adults. Adacel's weaker formulation was designed to reduce this reactogenicity while maintaining some immune response.

This raises a downstream question: if the higher antigen dose is too reactogenic for older bodies, why is it considered safe for the much smaller bodies of infants who receive the full Infanrix dose five times in the first six years of life?


Boostrix (GSK)

FieldValue
Licensed2005
Trial populationNot specified in source
Control groupDecavac (Td vaccine, Sanofi) — not licensed on placebo trial

Source: FDA-approved package insert; GSK licensure submission.

Cross-Manufacturer Control

Boostrix (a GSK product) was licensed against Decavac (a Sanofi product) — the same control used for Adacel. Both products are "as safe as" Decavac. Decavac's own safety was not established through a placebo-controlled trial.


Decavac — The Shared Control

Decavac is a Td (tetanus-diphtheria) vaccine manufactured by Sanofi. It was not licensed on a placebo-controlled trial. The safety of both Tdap brands therefore traces back through Decavac to no validated baseline — consistent with the overall pattern across the schedule.


Summary Table

BrandLicensedControlPlacebo?Antigen vs. DTaP
Adacel (Sanofi)2005Decavac (Td)NO12.5× less D / 10× less PT
Boostrix (GSK)2005Decavac (Td)NOReduced

Schedule

PopulationTiming
Adolescents11–12 years (single dose)
Adults not previously vaccinatedSingle dose Tdap, then Td every 10 years
Pregnant womenEach pregnancy (27–36 weeks gestation)
Caregivers of infantsSingle dose if not previously vaccinated ("cocooning")

Disease Context

Tetanus is environmental (soil exposure) and not person-to-person transmissible. Diphtheria has been functionally eradicated in the US for decades. Pertussis (whooping cough) continues to circulate in highly vaccinated populations because the vaccine does not prevent transmission. The adolescent Tdap booster was added because of waning immunity from childhood DTaP vaccination. The pregnancy Tdap recommendation aims to transfer maternal antibodies across the placenta to protect newborns in their first months of life.


See Also

Tdap Vaccines (Post-Licensure), Pre-Licensure Safety Testing, DTaP Vaccines (Pre-Licensure), Childhood Vaccine Schedule, Herd Immunity, Sanofi, GSK


Frequently Asked Questions

Frequently Asked Questions

Was the Tdap vaccine tested against a placebo?
No. Both Adacel (Sanofi) and Boostrix (GSK), licensed in 2005, were tested against Decavac — a Td (tetanus-diphtheria) vaccine manufactured by Sanofi. Decavac was not itself licensed via a placebo-controlled trial. Neither Tdap vaccine has a safety profile anchored to an inert baseline. This is documented in both products' FDA-approved package inserts.
Why does the Tdap vaccine contain less antigen than the infant DTaP vaccine?
Adacel contains 12.5 times less diphtheria toxoid and 10 times less pertussis toxin than the infant DTaP formulation (Infanrix). This reduction was necessary because the full DTaP antigen load causes too many adverse reactions in adolescents and adults. This raises a question documented in the package insert data: if the higher dose is too reactogenic for older, larger bodies, why is it considered safe for the much smaller bodies of infants who receive the full dose five times in six years?
What was the control group for Boostrix and Adacel clinical trials?
Both Boostrix (GSK) and Adacel (Sanofi) used Decavac (Sanofi's Td vaccine) as their control. This means a GSK product and a Sanofi product were both benchmarked against the same Sanofi Td vaccine. Decavac's own safety was never established through a placebo-controlled trial. Both Tdap vaccines are "as safe as" Decavac, and Decavac is "as safe as" nothing validated against an inert baseline.
Is the Tdap vaccine given during pregnancy?
Yes. The CDC recommends Tdap vaccination during every pregnancy, between 27 and 36 weeks gestation, to transfer maternal antibodies across the placenta to protect newborns. However, neither Adacel nor Boostrix was originally tested in pregnant women during their pre-licensure trials. The pregnancy recommendation was added after licensure based on observational data, not randomized controlled trial evidence with a placebo group.
Does the Tdap vaccine prevent pertussis transmission?
No. The Tdap vaccine does not prevent transmission of pertussis. A 2013 FDA baboon study showed that vaccinated animals continued to carry and transmit pertussis bacteria despite being protected from symptomatic disease. A 2018 world expert consensus confirmed this finding, and the CDC's own website acknowledges that Tdap does not block pertussis transmission. This undermines the "cocooning" rationale for vaccinating pregnant women and caregivers.