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 ce ll 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 ma ke the DTPw vaccine suitable for combination with hepatitis B and Haem ophilus influenzae b vaccines. Methods: Double blind randomized contro lled trial in suburban Melbourne in 812 healthy infants recruited thro ugh maternal and child health centres, of whom 208 received Triple Ant igen and 604 received nDTPw. Results: Results for both reactogenicity and immunogenicity were similar and were not significantly different f or 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(T M) (11%, P = 0.06). An elevated temperature (greater than or equal to 38 degrees C axillary) occurred in about three out of 10 babies overal l, 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 compar ed to 20% of Triple Antigen(TM) subjects (P = 0.015, 95% CI on differe nce 2%, 19%). Swelling after doses one and three occurred in 30% and 2 4% of Triple Antigen(TM) subjects, compared to 23% (P = 0.07, 95% CI d iff 0%, 13%) and 14% (P = 0.017, 95% CI diff 2%, 17%) of nDTPw subject s. Tenderness after doses two and three occurred in 80%, and 78% of Tr iple 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 we re significantly higher for Agg2, Fha, and pertactin compared to Tripl e Antigen(TM) geometric mean titres (GMTs). Conclusion: nDTPw is a saf e and immunogenic vaccine when compared to Triple Antigen(TM). The ref ormulated vaccine is an acceptable replacement for the currently marke ted formulation, and for evaluation as a component of future combinati on vaccines.