SAFETY AND IMMUNOGENICITY OF A BIVALENT HAEMOPHILUS-INFLUENZAE TYPE-BHEPATITIS-B VACCINE IN HEALTHY INFANTS

Objective, To assess the safety, tolerability and immunogenicity of CO MVAX(TM), 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 Bib vaccine, PedvaxHIB(R), and the yeast-derived hepatitis B surface antig en (HBsAg) used in the IIB vaccine, RECOMBIVAX HB(R). Design. Eight hu ndred eighty-two healthy infants, similar to 2 months of age, were enr olled in an open, multicenter (n = 11) clinical trial and randomized t o receive either COMVAX(TM) (7.5 mu g of PRP/5 mu g of HBsAg in 0.5 mi ) or concurrent injections of the liquid formulation of Pedvax-HIB(R) (P) (7.5 mu g of PRP in 0.5 mi) and RECOMBIVAX HB(R) (R) (5 mu g of HB sAg in 0.5 mi) at 2, 4 and 12 or 15 months of age, Safety and tolerabi lity 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 vac cination, Results. COMVAX(TM) was well-tolerated and proved to be immu nologically comparable with a series of concomitant P+R injections, Th ere were no serious adverse experiences attributable to the study vacc ines. The most commonly reported nonserious adverse experiences were a ll events prelisted on diary cards given to parents, These included ge nerally mild and transient signs of inflammation at the injection site (pain/soreness, erythema, swelling/induration), somnolence and irrita bility, Because children are at peak risk of invasive Bib disease duri ng 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 rega rd to the development of anti-PRP, At that time 94.8% of the infants g iven COMVAX(TM) had >0.15 mu g/ml of anti-PRP and 72.4% had >1.0 mu g/ mi, with a geometric mean concentration (GMC) of 2.5 mu g/ml, compared with 95.2%, 76.3% and 2.8 mu g/ml, respectively, in recipients of P+R , The third injection given at 12 or 15 months of age induced a second ary rise in antibody, The proportions with >0.15 mu g/ml and >1.0 mu g /ml of anti-PRP increased to 99.3 and 92.6%, respectively, and the GMC rose to 9.5 mu g/ml among COMVAX(TM) recipients, compared with 98.9%, 92.3% and 10.2 mu g/ml in children given concurrent injections of P+R , In contrast to Bib few infants in countries with low endemicity of H BV infection are at near term risk of exposure to virus, Consequently the anti-HBs response after the last dose of vaccine was designated th e outcome of primary interest, At 13 to 16 months of age (1 month afte r the third dose of vaccine) 98.4% of children given COMVAX(TM) had a protective anti-HBs concentration of greater than or equal to 10 mIU/m l with a GMC of 4468 mIU/ml, compared with 100% and a GMC of 6944 mIU/ ml among children given P+R. Conclusions, COMVAX(TM) is well-tolerated by healthy infants and can induce immunity against invasive Bib disea se and HBV infection using only three injections compared with six inj ections if separate courses of monovalent Pedvax -HIB(R) and RECOMBIVA X HB(R) are given.