Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations.

UNLABELLED: With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative, multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available Haemophilus influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus- acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one of the following groups: (1) separate, or (2) mixed injection of DTaP and candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib vaccine. One year later the first 189 study subjects received either separate or mixed injections of the same Hib and DTaP vaccines as booster doses. Evaluation of reactogenicity was based on diary cards completed by parents. Immunogenicity was documented by measuring IgG antibody concentrations in serum samples taken before and 4 weeks after primary and booster vaccination. No serious adverse events occurred and most local and systemic reactions were mild to moderate. Booster doses were more reactogenic than primary doses with all groups. Antibody concentrations against pertussis antigens were similar to those seen with DTaP alone. All but one subject had protective antibody concentrations against diphtheria and tetanus. Primary immune response to the Hib vaccine was significantly lower in the group receiving the mixed Hib-DTaP vaccine, however, > or = 95% of vaccinees had anti-Hib antibody concentrations > or = 0.15 microg/ml and there was a marked booster response (> 100-fold) in all groups. CONCLUSIONS: Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti-Hib antibody response, although after primary immunization as after booster doses, all subjects showed antibody concentrations considered to be protective for invasive Hib disease. Mixing of the vaccines did not result in increased reactogenicity.

Safety and efficacy of acellular pertussis vaccines: the Mainz study and other recent studies.

Following concerns about the safety and reactogenicity profile of diphtheria, tetanus and whole cell pertussis vaccines (DTwP), new and less reactogenic alternatives were developed over the last two decades. The new diphtheria, tetanus and acellular pertussis vaccines (DTaP) no longer consist of the whole bacterial cell but of either extracts or of a few highly purified components. While it soon became clear that DTaP vaccines are significantly less reactogenic than DTwP vaccines, their efficacy was disputed and remained unproven. First studies and epidemiological data from Japan suggested vaccine efficacy rates (VE) of about 80%; however, the first blinded clinical trial from Sweden documented a much lower VE. Worldwide, seven large DTaP efficacy trials have recently been completed. Our own efforts included a large safety trial with 22505 vaccinees and, nested in this setting, a prospective household contact study. Typical WHO-defined pertussis developed in 7 of 112 DTaP vaccinated children following household exposure as compared to 96 cases in 173 children not vaccinated against pertussis. Thus, vaccine efficacy was calculated to be 88.7% (95% CI 76.6 to 94.6). The median duration of spasmodic cough in the few children vaccinated with DTaP who did start coughing was 17 days as compared to 35 days in unvaccinated children. No waning of protection was observed. None of the confounding variables analyzed influenced study results in favour of DTaP. Following administration of more than 67000 DTaP doses, 153 serious adverse events were reported. Eight events were considered possibly related and five were considered related to the study vaccine. According to additional study results from the other trials it can be concluded that DTaP vaccines, like DTwP vaccines, are safe and effective. The choice between DTwP and DTaP should be based on acceptance of the reactogenicity profile, coverage rates achieved, costs and other factors in each individual country.

Reactogenicity and immunogenicity of a booster dose of a combined diphtheria, tetanus, and tricomponent acellular pertussis vaccine at fourteen to twenty-eight months of age.

OBJECTIVES: The primary objective was to assess the nature and incidence of adverse events after a fourth dose of a tricomponent acellular pertussis-diphtheriatetanus vaccine given in the second year of life after primary vaccination with the same vaccine at 3, 4, and 5 months of age. A secondary objective was to analyze the immunogeniecity of the booster vaccination. DESIGN: Of the 5361 children enrolled (aged 14 to 28 months), adverse reactions were specifically solicited from the first 1863 enrollees for the first 4 days after vaccination and then were unsolicited for the remainder of the 4 weeks of follow-up (group 1). In the next 3498 subjects, safety and reactogenicify were entirely unsolicited for this 4-week period (group 2). Immunogenicity was analyzed by means of prebooster and postbooster serum antibody titers for all vaccine components in a random subgroup of 197 children from group 1. RESULTS: Soliciting symptoms elicited reports of at least one symptom in 1314 of 1809 children in group 1 (72.6%), including 993 (54.9%) with local and 885 (48.9%) with general symptoms during the first 4 days after vaccination. When symptoms were gathered in an unsolicited fashion, only 580 of 3498 children in group 2 (16.6%) had a reported symptom during this time, consisting of 344 (9.8%) local and 319 (9.1%) general symptoms, respectively. An unsolicited symptom, areactive edematous swelling of the whole thigh, occurred in 62 children (1.1%), with 45 and 17 reports in groups 1 and 2, respectively. The vast majority of all reported symptoms were mild to moderate, and all children recovered without sequelae. Fourteen serious adverse events were reported, but none was considered to be related to the vaccination. Immunogenicity analysis showed a vaccine response to pertussis toxin in 99.5% of subjects, to filamentous hemagglutinin in 98.5%, and to pertactin (69 kd outer membrane protein) in 99%. All subjects had postvaccination antibody titers of 0.1 IU/ml or greater against diphtheria and tetanus toxoids.