Antibody responses of healthy infants to concurrent administration of a bivalent haemophilus influenzae type b-hepatitis B vaccine with diphtheria-tetanus-pertussis, polio and measles-mumps-rubella vaccines.

OBJECTIVE: To confirm that children given a bivalent Haemophilus influenzae type b-hepatitis B vaccine (bivalent Hib-HB vaccine; COMVAX) concurrently with priming doses of diphtheria-tetanus-pertussis vaccine (DTP), a booster dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP), inactivated or oral polio vaccine (IPV or OPV) and measles-mumps-rubella vaccine (M-M-R(II)) have satisfactory antibody responses to all antigens. DESIGN: 126 healthy 2-month-old infants were scheduled to receive bivalent Hib-HB vaccine concurrently with DTP (2 and 4 months of age), OPV or IPV (random allocation to OPV or IPV at 2 months of age; OPV at 4 and 14 to 15 months of age), DTaP and M-M-R(II) (14 to 15 months of age). A response was judged "adequate" if the lower bound of the 95% confidence interval on the proportion of vaccinees having a critical antibody level was <10 percentage points below prediction. RESULTS: Antibodies to hepatitis B virus surface antigen, H. influenzae polysaccharide, diphtheria toxin, tetanus toxin, pertussis agglutinogens, pertussis toxin (as measured by enzyme immunoassay but not by Chinese hamster ovary cell assay), pertussis filamentous haemagglutinin after a booster dose of DTaP, poliovirus type 2, measles virus, and mumps virus all equalled or exceeded expected levels. Antibodies to rubella virus and pertussis filamentous haemagglutinin (after priming doses of DTP) fell slightly, and in the case of rubella significantly, below predicted levels. Antibodies to poliovirus types 1 and 3 were also below expectation after 2 doses of polio vaccine but were adequate following a third dose of vaccine. CONCLUSION: Concurrent administration of bivalent Hib-HB vaccine with priming doses of DTP, a booster dose of DTaP, OPV, IPV, or M-M-R(II) was well tolerated and, with the possible exception of rubella, did not substantially impair the antibody response to any antigen.

A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults.

This study shows that two doses of a recombinant hepatitis B vaccine (10 micrograms or 20 micrograms of HBsAg per dose), administered 6 months apart to young, healthy adults, can induce an antibody (anti-HBs) response similar to that expected with the standard three-dose regimen of this vaccine given at intervals of 0, 1, and 6 months. While only 46-67% of the vaccinees displayed a protective anti-HBs titer of > or = 10 mIU ml-1 prior to the receipt of the second dose at 6 months, virtually all were primed as 97-99% of the subjects developed such a titer when tested a month after the second dose. Among vaccinees given 10 or 20 microgram doses, respectively, the secondary rise in antibody following the second dose yielded geometric mean titers (GMTs) of 1103 and 2538 mIU ml-1, respectively. The study further demonstrated that a two-dose regimen of vaccination induced strong immunologic memory for HBsAg, as a booster dose of vaccine given 2 years later resulted in a rapid and vigorous anamnestic antibody response.

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.

Antibody responses of healthy infants to a recombinant hepatitis B vaccine administered at two, four, and twelve or fifteen months of age.

Hepatitis B vaccine was administered to healthy infants on two investigational schedules that fall within ranges recommended by the U.S. Public Health Service Advisory Committee on Immunization Practices and by the American Academy of Pediatrics Committee on Infectious Diseases. A month after receiving vaccine at 2, 4, and 12 or 15 months of age, 98% and 100% of the children had > 10 mIU antibodies to hepatitis B surface antigen per milliliter, with gemometric mean titers of 1358 mIU/ml and 3424 mIU/mL, respectively.

Control of hepatitis B through routine immunization of infants: the need for flexible schedules and new combination vaccine formulations.

Universal immunization of infants is essential to the control of hepatitis B in areas of high endemicity where infection commonly occurs in infants and children. It is also an attractive strategy for ultimately reducing hepatitis-B-associated acute and chronic liver disease in areas of lower endemicity where infections occur primarily in adolescents and adults. Integration of hepatitis B vaccine with other routine paediatric immunizations, using flexible scheduling, will enhance compliance while minimizing the need for additional resources. Clinical studies demonstrate that a very high proportion of healthy infants and adults develop a protective level of antibody when given hepatitis B vaccine using a wide range of schedules. Compliance with universal vaccination of infants against hepatitis B may be enhanced by the development of new combination vaccines (e.g. diphtheria-tetanus-pertussis-Haemophilus influenzae b-hepatitis B) that allow complete immunization against several antigens with a minimal number of injections.