Primary course immunogenicity and reactogenicity of a new diphtheria-tetanus-whole cell pertussis vaccine (DTPw).

Objective: To establish safety, immunogenicity, and batch stability of a reformulated whole cell pertussis based diphtheria-tetanus-whole cell pertussis (DTP) vaccine (nDTPw) compared to the currently marketed Australian DTPw vaccine (Triple Antigen(TM)) in a three dose 2, 4 and 6 month primary immunization course. Reformulation was necessary to make the DTPw vaccine suitable for combination with hepatitis B and Haemophilus influenzae b vaccines. Methods: Double blind randomized controlled trial in suburban Melbourne in 812 healthy infants recruited through maternal and child health centres, of whom 208 received Triple Antigen and 604 received nDTPw. Results: Results for both reactogenicity and immunogenicity were similar and were not significantly different for the three batches of nDTPw. No new, serious, or unexpected adverse effect was recorded. Nearly twice as many nDTPw infants experienced no general reaction to the third dose (18%) compared to Triple Antigen(TM) (11%, P = 0.06). An elevated temperature (greater than or equal to 38 degrees C axillary) occurred in about three out of 10 babies overall, with rates being slightly higher for both vaccines after the second vaccination. Local reaction rates were significantly less common for nDTPw on days 2 and 3 following each of the three vaccinations. After dose three, 30% of nDTPw subjects experienced no local reaction compared to 20% of Triple Antigen(TM) subjects (P = 0.015, 95% CI on difference 2%, 19%). Swelling after doses one and three occurred in 30% and 24% of Triple Antigen(TM) subjects, compared to 23% (P = 0.07, 95% CI diff 0%, 13%) and 14% (P = 0.017, 95% CI diff 2%, 17%) of nDTPw subjects. Tenderness after doses two and three occurred in 80%, and 78% of Triple Antigen(TM) subjects, compared to 71% (P = 0.04, 95% CI diff 1%, 17%) and 68% (P = 0.025, 95% CI diff 2%, 19%) of nDTPw subjects. There was a significantly higher post immunization diphtheria antitoxin GMT (2.73 IU/mL) for Triple Antigen(TM) compared to nDTPw (1.89 IU/mL; P = 0.02), although no subject in either vaccine group had a tetanus or diphtheria antibody titre less than six times the protective level of 0.01 IU/mL following immunization. The nDTPw post immunization GMTs were significantly higher for Agg2, Fha, and pertactin compared to Triple Antigen(TM) geometric mean titres (GMTs). Conclusion: nDTPw is a safe and immunogenic vaccine when compared to Triple Antigen(TM). The reformulated vaccine is an acceptable replacement for the currently marketed formulation, and for evaluation as a component of future combination vaccines.