Each infant in this study received two doses of either placebo or lyophilized PedvaxHIB (15 mcg Haemophilus b PRP) with the first dose administered at a mean of 8 weeks of age and the second administered approximately two months later; DTP (Diphtheria and Tetanus Toxoids and whole cell Pertussis Vaccine, Adsorbed) and OPV (Poliovirus Vaccine Live Oral Trivalent) were administered concomitantly. In a subset of 416 subjects, lyophilized PedvaxHIB (15 mcg Haemophilus b PRP) induced anti-PRP levels > 0.15 mcg/mL in 88% and > 1.0 mcg/mL in 52% with a geometric mean titer (GMT) of 0.95 mcg/mL one to three months after the first dose; the corresponding anti-PRP levels one to three months following the second dose were 91% and 60%, respectively, with a GMT of 1.43 mcg/mL. These antibody responses were associated with a high level of protection.

Most subjects were initially followed until 15 to 18 months of age. During this time, 22 cases of invasive Hib disease occurred in the placebo group (8 cases after the first dose and 14 cases after the second dose) and only 1 case in the vaccine group (none after the first dose and 1 after the second dose).

Following the primary two-dose regimen, the protective efficacy of lyophilized PedvaxHIB was calculated to be 93% with a 95% confidence interval (C.I.) of 57-98%. In the two months between the first and second doses, the difference in number of cases of disease between placebo and vaccine recipients (8 vs 0 cases, respectively) was statistically significant (p=0.008). At termination of the study, placebo recipients were offered vaccine. All original participants were then followed two years and nine months from termination of the study. During this extended follow-up, invasive Hib disease occurred in an additional 7 of the original placebo recipients prior to receiving vaccine and in 1 of the original vaccine recipients (who had received only 1 dose of vaccine). No cases of invasive Hib disease were observed in placebo recipients after they received at least one dose of vaccine. Efficacy for this follow-up period, estimated from person-days at risk, was 96.6% (95 C.I., 72.2-99.9%) in children under 18 months of age and 100% (95 C.I., 23.5-100%) in children over 18 months of age.31 Thus, in this study, a protective efficacy of 93% was achieved with an anti-PRP level of > 1.0 mcg/mL in 60% of vaccinees and a GMT of 1.43 mcg/mL one to three months after the second dose.

Hepatitis B Disease

Hepatitis B virus is an important cause of viral hepatitis. According to the Centers for Disease Control (CDC), there are an estimated 200,000-300,000 new cases of Hepatitis B infection annually in the United States.³² There is no specific treatment for this disease. The incubation period for hepatitis B is relatively long; six weeks to six months may elapse between exposure and the onset of clinical symptoms. The prognosis following infection with hepatitis B virus is variable and dependent on at least three factors: (1) Age — infants and younger children usually experience milder initial disease than older persons but are much more likely to remain persistently infected and become at risk of developing serious chronic liver disease; (2) Dose of virus — the higher the dose, the more likely acute icteric hepatitis B will result; and, (3) Severity of associated underlying disease — underlying malignancy or pre-existing hepatic disease predisposes to increased mortality and morbidity.³⁴

Hepatitis B infection fails to resolve and progresses to a chronic carrier state in 5 to 10% of older children and adults and in up to 90% of infants; chronic infection also occurs more frequently after initial anicteric hepatitis B than after initial icteric disease.³⁴ Consequently, carriers of HBsAg frequently give no history of having had recognized acute hepatitis. It has been estimated that more than 285 million people in the world today are persistently infected with hepatitis B virus.³⁵ The CDC estimates that there are approximately 1 million-1.25 million chronic carriers of hepatitis B virus in the USA.³² Chronic carriers represent the largest human reservoir of hepatitis B virus.

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