Safety and immunogenicity of a bivalent Haemophilus influenzae type b/hepatitis B vaccine in healthy infants. Hib-HB Vaccine Study Group.

OBJECTIVE: To assess the safety, tolerability and immunogenicity of COMVAX, a liquid, bivalent Haemophilus influenzae type b-hepatitis B vaccine, containing the polyribosylribitol phosphate (PRP)-Neisseria meningitidis outer membrane protein complex conjugate used in the Hib vaccine, PedvaxHIB, and the yeast-derived hepatitis B surface antigen (HBsAg) used in the HB vaccine, RECOMBIVAX HB. DESIGN: Eight hundred eighty-two healthy infants, approximately 2 months of age, were enrolled in an open, multicenter (n = 11) clinical trial and randomized to receive either COMVAX (7.5 micrograms of PRP/5 micrograms of HBsAg in 0.5 ml) or concurrent injections of the liquid formulation of PedvaxHIB (P) (7.5 micrograms of PRP in 0.5 ml) and RECOMBIVAX HB (R) (5 micrograms of HBsAg in 0.5 ml) at 2, 4 and 12 or 15 months of age. Safety and tolerability were monitored after each injection. The serum concentrations of anti-PRP and anti-HBs were determined at the time of each vaccination, 2 months after the second vaccination and 1 month after the third vaccination. RESULTS: COMVAX was well-tolerated and proved to be immunologically comparable with a series of concomitant P+R injections. There were no serious adverse experiences attributable to the study vaccines. The most commonly reported nonserious adverse experiences were all events prelisted on diary cards given to parents. These included generally mild and transient signs of inflammation at the injection site (pain/ soreness, erythema, swelling/induration), somnolence and irritability. Because children are at peak risk of invasive Hib disease during the first year of life, 6 months of age (2 months after the second dose of vaccine) was designated the time of primary interest with regard to the development of anti-PRP. At that time 94.8% of the infants given COMVAX had > 0.15 microgram/ml of anti-PRP and 72.4% had > 1.0 microgram/ ml, with a geometric mean concentration (GMC) of 2.5 micrograms/ml, compared with 95.2%, 76.3% and 2.8 micrograms/ml, respectively, in recipients of P+R. The third injection given at 12 or 15 months of age induced a secondary rise in antibody. The proportions with > 0.15 microgram/ml and > 1.0 microgram/ml of anti-PRP increased to 99.3 and 92.6%, respectively, and the GMC rose to 9.5 micrograms/ml among COMVAX recipients, compared with 98.9%, 92.3% and 10.2 micrograms/ml in children given concurrent injections of P+R. In contrast to Hib few infants in countries with low endemicity of HBV infection are at near term risk of exposure to virus. Consequently the anti-HBs response after the last dose of vaccine was designated the outcome of primary interest. At 13 to 16 months of age (1 month after the third dose of vaccine) 98.4% of children given COMVAX had a protective anti-HBs concentration of > or = 10 mIU/ml with a GMC of 4468 mIU/ml, compared with 100% and a GMC of 6944 mIU/ml among children given P+R. CONCLUSIONS: COMVAX is well-tolerated by healthy infants and can induce immunity against invasive Hib disease and HBV infection using only three injections compared with six injections if separate courses of monovalent PedvaxHIB and RECOMBIVAX HB are given.