Immunogenicity and reactogenicity of acellular diphtheria/tetanus/pertussis vaccines given as a pre-school booster: effect of simultaneous administration of MMR.

Four acellular diphtheria/tetanus/pertussis (aDTP) vaccines were compared with two diphtheria/tetanus (DT) vaccines given as a pre-school booster to 1033 children aged 4 to < 6 years who had completed primary immunisation with DTP vaccine according to the UK 2, 3 and 4 month schedule; 71 children had received aDTP vaccine and the remaining 962 a whole cell DTP vaccine for primary immunisation. The effect of simultaneous administration of a second dose of MMR vaccine was evaluated in 374 (37%). Overall, there was little difference in the frequency of post-vaccination symptoms in DT and aDTP vaccinees, although local reactions occurred more quickly in the aDTP group. The concomitant administration of MMR had no effect on local reactions or fever within 10 days, or on the proportions requiring a doctor's visit in the 4--6 week post-vaccination period. Local reactions > or = 3 cm were higher on day 2 in children who had received aDTP for primary immunisation (erythema 32.4% vs. 17.4% for wDTP, P = 0.0012; swelling 28.2% vs. 15.5%, P = 0.0027). Pertussis antibody responses were consistent with the antigen content of the aDTP vaccines. All were more immunogenic with respect to PT -- the only pertussis antigen which by itself has been shown to be protective in clinical trials -- than a wDTP pre-school booster given in an earlier trial. MMR vaccine had no significant effect on antibody responses to either the pertussis or diphtheria and tetanus antigens. Diphtheria antibody responses in children who had received wDTP for primary immunisation were 2.8 times higher than in those who had received aDTP vaccine (P < 0.0001); they were also higher in children who had received a single dose of a Haemophilus influenzae type b vaccine containing CRM(197) conjugate after 12 months of age. For countries currently using DT vaccines as a pre-school booster, replacement with an aDTP vaccine is unlikely to have a perceptible effect on reactogenicity, at least in children given wDTP for primary immunisation, and would boost antibody levels to antigens known to be associated with protection.