A combined liquid Hib (PRP-OMP), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: uncontrolled preliminary clinical trial of immunogenicity and reactogenicity

Abstract

We have conducted a preliminary uncontrolled clinical trial of the immunogenicity and reactogenicity of a new fully liquid pentavalent combination vaccination which incorporates a diphtheria, tetanus and whole-cell pertussis vaccine with Hib (PRP-OMP) and hepatitis B vaccines. Forty-five infants received three doses of the pentavalent vaccination at 2, 4, and 6 months of age, and then a fourth dose at 18 months of age. Subjects were bled prior to each vaccination, and a month after the third and fourth vaccinations. A 7-day diary card was used to record subject temperatures and other systemic and local clinical signs after each vacination. After the third dose, 98% of subjects had anti-PRP titres above 1 μg ml −1 (95%ci 88%, 100%). Following boosting, the geometric mean titre (GMT) rose a mean 27-fold (95%ci 19-fold, 38-fold) to 33 μg ml −1, and all subjects' titres (lower bound of 95%ci 92%) exceeded 1 μg ml −1. For hepatitis B antibody, there was a GMT of 100 mIU ml −1 after the third dose, and 86% of infants (95%ci 73%, 95%) had antibody levels ≥ 10 mIU ml −1. After the fourth dose, there was a mean 77-fold boost (95%ci 48-fold, 130-fold) to a GMT of 860 mIU ml −1 and 95% (95%ci 84%, 99%) of subjects had titres ≥ 10 mIU ml −1. Diphtheria, tetanus, and pertussis antibody levels were all at acceptable levels after the first three doses and again after the fourth vaccination. The pentavalent vaccine was well tolerated at all administration times, and had a minor reactogenicity profile similar to DTPw alone as reported in previous studies. This study has provided preliminary evidence for both the safety and immunogenicity of the pentavalent vaccine given as a course at 2, 4, 6 and 18 months.