Prior to the introduction of Haemophilus b Conjugate Vaccines, Haemophilus influenzae type b (Hib) was the most frequent cause of bacterial meningitis and a leading cause of serious, systemic bacterial disease in young children worldwide.^1,2,3,4

Hib disease occurred primarily in children under 5 years of age in the United States prior to the initiation of a vaccine program and was estimated to account for nearly 20,000 cases of invasive infections annually, approximately 12,000 of which were meningitis. The mortality rate from Hib meningitis is about 5%. In addition, up to 35% of survivors develop neurologic sequelae including seizures, deafness, and mental retardation.^5,6 Other invasive diseases caused by this bacterium include cellulitis, epiglottitis, sepsis, pneumonia, septic arthritis, osteomyelitis and pericarditis.

Prior to the introduction of the vaccine, it was estimated that 17% of all cases of Hib disease occurred in infants less than 6 months of age.⁷ The peak incidence of Hib meningitis occurs between 6 to 11 months of age. Forty-seven percent of all cases occur by one year of age with the remaining 53% of cases occurring over the next four years.^2,20

Among children under 5 years of age, the risk of invasive Hib disease is increased in certain populations including the following:

• Daycare attendees^8,9
• Lower socio-economic groups¹⁰
• Blacks¹¹ (especially those who lack the Km(1) immunoglobulin allotype)¹²
• Caucasians who lack the G2m(n or 23) immunoglobulin allotype¹³
• Native Americans^14,15,16
• Household contacts of cases¹⁷
• Individuals with asplenia, sickle cell disease, or antibody deficiency syndromes^18,19

An important virulence factor of the Hib bacterium is its polysaccharide capsule (PRP). Antibody to PRP (anti-PRP) has been shown to correlate with protection against Hib disease.^3,21 While the anti-PRP level associated with protection using conjugated vaccines has not yet been determined, the level of anti-PRP associated with protection in studies using bacterial polysaccharide immune globulin or nonconjugated PRP vaccines ranged from > 0.15 to > 1.0 mcg/mL.^22-28

Nonconjugated PRP vaccines are capable of stimulating B-lymphocytes to produce antibody without the help of T-lymphocytes (T-independent). The responses to many other antigens are augmented by helper T-lymphocytes (T-dependent). PedvaxHIB is a PRP-conjugate vaccine in which the PRP is covalently bound to the OMPC carrier²⁹ producing an antigen which is postulated to convert the T-independent antigen (PRP alone) into a T-dependent antigen resulting in both an enhanced antibody response and immunologic memory.

Clinical Evaluation of PedvaxHIB

PedvaxHIB, in a lyophilized formulation (lyophilized PedvaxHIB), was initially evaluated in 3,486 Native American (Navajo) infants, who completed the primary two-dose regimen in a randomized, double-blind, placebo-controlled study (The Protective Efficacy Study). At the time of the study, this population had a much higher incidence of Hib disease than the United States population as a whole and also had a lower antibody response to Haemophilus b Conjugate Vaccines, including PedvaxHIB.^{14,15,16,30,33}

Each infant in this study received two doses of either placebo or lyophilized PedvaxHIB with the first dose administered at a mean of 8 weeks of age and the second administered approximately two months later; DTP and OPV were administered concomitantly. Antibody levels were measured in a subset of each group (TABLE 1).

TABLE 1
Antibody Responses in Navajo Infants

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