Safety and immunogenicity of a combination DTPa-Hepatitis B vaccine (DTPa-Hep B) administered to infants at 2,4 and 6 months of age

To reduce the number of injections required during infancy, DTPa-Hep B vaccine was developed. However, there are concerns that administration of Hep B vaccine at 2, 4 and 6 months of age induces poorer antibody responses than those with schedules that have longer intervals b/w the 2nd and 3rd doses. To address this issue, 280 infants were randomized to receive; Grp 1) DTPa-Hep B vaccine at 2,4 and 6 mo. or Grp 2) DTPa vaccine at 2, 4 and 6 mo, and hep B vaccine at birth, 1 and 6 mo. Hib (PRP-T) and OPV vaccines were given at 2,4 and 6 months at separate sites. Pre and post immunization bloods were obtained and adverse events were carefully assessed. Reactions were generally mild and none of the differences b/w groups were thought to be clinically significant. No vaccine attributable serious events occurred. There were no significant differences in pre-antibody concentrations (GMTs) b/w the two groups. Below are the preliminary GMTs after the third dose (at 7 mo of age): N Hep B Diph Tet PT FHA PRN PRP Units/mL mIU IU IU EL.U EL.U EL.U μg Grp l 49 1280* 1.93 3.82 72.3 459 195 7.75 Grp 2 59 4620 1.00 2.11 52.2 334 138 6.52 p value <001 <.001 <001 <01 <01 .03 NS*At 7 mo, 98% and 100% of subjects had Hep B titers > 10 mIU/mL inGrps 1 and 2, respectively. DTPa-Hep B vaccine was safe, and for most antigens it induced significantly greater antibody responses compared with DTPa vaccine alone. The DTPa-Hep B vaccine given at 2-4-6 mo induced significantly lower Hep B antibody responses compared with Hep B vaccine given at birth-1-6 mo, but 98% achieved protective levels of antibody. Despite the shorter interval b/w doses, DTPa-Hep B was immunogenic and should be used in the development of future combination vaccines.