Reactogenicity and immunogenicity of reduced antigen content diphtheria-tetanus-acellular pertussis vaccines as a booster in 4-7-year-old children primed with diphtheria-tetanus-whole cell pertussis vaccine before 2 years of age.

BACKGROUND: The recent introduction of acellular pertussis vaccines (Pa) offers the possibility of booster doses in older children and adults. This can be conveniently accomplished by combining acellular pertussis antigens with diphtheria and tetanus toxoids. However the optimal dosage for the booster injection has not yet been determined. OBJECTIVE: To compare the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis vaccines (DTPa) with lower antigen contents to a licensed DTPa vaccine when given at 4-7 years of age as a booster to DTPw-primed children. METHODS: Two hundred and twenty-six children primed with four doses of DTPw before 2 years of age were enrolled and allocated to three groups to receive one dose of either DTPa (Infanrix, SmithKline Beecham, Biologicals), a reduced antigen formulation of this vaccine (dtpa, SmithKline Beecham Biologicals), or an experimental low dose formulation (dtpa-exp; d and t, Michigan Biologic Products Institute). Reactogenicity was assessed using diary cards for 15 days. Immunogenicity was determined as antibody responses against the vaccine components in pre- and 1 month postvaccination sera. RESULTS: Of the 225 children who completed the study, 60.0-66.7% reported symptoms, with no significant differences in rates between groups. Local, systemic and unsolicited symptoms occurred with similar frequencies in all three groups, the vast majority (> 90%) being considered as mild or moderate. No serious adverse events related to vaccination were reported. After vaccination, all subjects displayed seroprotective concentrations against diphtheria and tetanus, and 98.7-100% had antibodies against the three pertussis component antigens. The group receiving the reduced dose of the licensed vaccine showed antibody concentrations comparable to those of the full dose group. However, the group receiving the experimental low dose formulation had statistically significantly lower antibody concentrations against both diphtheria and tetanus toxoids compared with the two other groups, as well as significantly lower anti FHA antibody concentrations. CONCLUSIONS: Reducing the antigen content of dtpa had no deleterious effect on the immunogenicity of the vaccine when given as a fifth dose at 4-7 years of age in DTPw-primed children. The reactogenicity profile of both the reduced antigen dtpa vaccines and DTPa were acceptable, the vast majority of local and systemic reactions being considered as mild to moderate, with no vaccine-related serious adverse events reported. The use of lower antigen content dtpa vaccine as a booster in children aged 4-7 is safe and immunogenic.

Overview of the clinical development of a diphtheria-tetanus--acellular pertussis vaccine.

A tricomponent acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, and pertactin combined with diphtheria and tetanus toxoids (DTPa) was developed as a less reactogenic alternative to the traditional whole cell pertussis (DTPw) vaccine. In studies of DTPa as a primary vaccination and as a booster dose in DTPa- or DTPw-primed children, the vaccine was safe, well-tolerated, and highly immunogenic; it was less reactogenic than DTPw but at least as immunogenic. A three-dose primary vaccination sequence with DTPa vaccine in the first 6 months of life protects against pertussis under conditions of high infectious pressure. These results support the licensing of the vaccine for primary and booster vaccination in a growing number of countries. Combined DTPa-based pediatric vaccines are in clinical development.