Combined, Reduced-Antigen Content Tetanus, Diphtheria, and Acellular Pertussis Vaccine (Boostrix®)

Summary

Abstract

Boostrix® is a three-pertussis component, combined, reduced-antigen content tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccine administered as a single intramuscular dose in adolescents or adults aged 10–64 years. Large, well designed trials conducted in the US in adolescents aged 10–18 years and in adults aged 19–64 years showed that serum concentrations of anti-pertussis antibodies ≈1 month after Boostrix® administration were noninferior to those previously shown to have a protective effect in infants following a primary regimen of combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccine. Protective serum concentrations of anti-diphtheria and anti-tetanus antibodies were achieved in essentially all (≥99.9%) adolescents randomized to receive Boostrix® or tetanus and diphtheria toxoids (Td) vaccine, and Boostrix® was noninferior to Td vaccine for these endpoints. Similarly high seroprotection rates against diphtheria and tetanus were demonstrated with Boostrix® and a five-pertussis component Tdap booster vaccine (Adacel®) in a large, randomized study in adults; Boostrix® was noninferior to Adacel® for these outcomes. Reactogenicity data indicate that the vaccine is generally well tolerated in terms of solicited local and general symptoms in both adults and adolescents. Moreover, the importance of single-dose booster vaccination with a Tdap vaccine (such as Boostrix®) in these populations is highlighted in current immunization guidelines. Therefore, as a single-dose booster vaccine, Boostrix® provides a useful option to reduce pertussis morbidity and maintain the standard of care for tetanus and diphtheria protection in individuals aged 10–64 years.

Immunogenicity

The immunogenicity of a single intramuscular booster dose of Boostrix® was demonstrated in two large, randomized, observer-blind studies, one comparing Boostrix® and Td vaccine in 4114 adolescents aged 10–18 years, and the other comparing Boostrix® and Adacel® in 2284 adults aged 19–64 years. In both trials, analysis of immunogenicity was conducted in the according-to-protocol cohort, which comprised ≈90–95% of the vaccinated cohort.

In both adolescents and adults, administration of Boostrix® was associated with marked increases in concentrations of anti-pertussis antibodies (anti-pertussis [anti-PT], anti-filamentous hemagglutinin [anti-FHA], and anti-pertactin [anti-PRN]) from pre-vaccination levels to those ≈1 month after vaccination. In adolescents, predefined criteria for booster responses ≈1 month after Boostrix® were met for all three antipertussis antibodies; in adults, criteria were met for anti-FHA and anti-PRN. Post-vaccination concentrations of anti-pertussis antibodies in adolescents and adults were noninferior to concentrations previously shown to have a protective effect in infants who had received a three-dose primary vaccination regimen of DTaP as part of a household contact study. This comparison was necessary because of the lack of serologic correlates of protection against pertussis.

Protective serum concentrations of anti-diphtheria and anti-tetanus antibodies (≥0.1IU/mL) were achieved in ≥99.9% of adolescents randomized to receive Boostrix® or Td vaccine, and the predefined criterion for noninferiority of Boostrix® to Td vaccine was met. Boostrix® was also noninferior to Td vaccine with respect to booster response rates for anti-diphtheria and anti-tetanus antibodies in adolescents. Boostrix® was similarly immunogenic in adults. When Boostrix® was compared with Adacel®, noninferiority was demonstrated for seroprotection against diphtheria and tetanus, as well as for the proportion of individuals with anti-tetanus antibody concentrations ≥1.0 IU/mL.

Additional studies suggest that concomitant administration of Boostrix® with other recommended vaccines may provide an effective strategy with practical advantages, such as convenience and improved compliance, although there was a diminution in some antibody responses. The immunogenicity of the pertussis components was decreased when Boostrix® and influenza vaccine were administered together (at different injection sites) in adults, similar to previous observations with co-administered Adacel® and influenza vaccine. In addition, there was some interference with pertussis antigen immunogenicity (anti-PRN concentrations) in the meningococcal conjugate vaccine (MCV4) co-administration study in adolescents.

Reactogenicity

Data on local and general adverse events were solicited using standardized diaries for the 15-day period after study vaccination in the large, randomized, observer-blind trial comparing Boostrix® and Td vaccine in adolescents, and in the similarly designed study comparing Boostrix® and Adacel® in adults. In adolescents, the incidence of any pain, and grade 2 or 3 pain, at the injection site was significantly higher with Boostrix® than with Td vaccine, although there was no significant between-group difference for grade 3 pain. There were no significant differences in the incidences of other local symptoms, such as redness and swelling, in adolescents. There were also no between-group differences in the incidences of general symptoms, such as headache, fatigue, gastrointestinal symptoms, and fever, although Boostrix® was associated with a significantly higher incidence of grade 2 or 3 headache than Td vaccine.

Boostrix® was generally associated with a lower incidence of local solicited symptoms than Adacel® in adults over the 15-day post-vaccination period. Significantly greater percentages of Adacel® than Boostrix® recipients reported pain, redness or swelling (of any grade), as well as grade 3 (≥50 mm) redness and swelling, at the injection site. The incidence of general solicited symptoms was broadly similar between the two treatment groups, although Boostrix® was associated with a significantly lower incidence of fever (≥37.5°1C) and a significantly higher incidence of grade 3 fatigue.

Boostrix® was also generally well tolerated when administered concomitantly with influenza vaccine in adults and with MCV4 vaccine in adolescents.