Commentary: Results of Efficacy Trials in Alaska and Finland of Haemophilus influenzae Type b Conjugate Vaccine

Abstract

One of the currently licensed Haemophilus influenzae type b polysaccharide conjugate vaccines currently recommended for use in children 18 months of age and older, polyribosylribitol-phosphate-diphtheria toxoid (PRP-D, Connaught Laboratories), has been evaluated in two studies for its protective efficacy in children immunized before 6 months of age.1 The peak incidence of invasive disease caused by H. influenzae type b occurs in children 6 to 18 months of age; therefore, prevention of this disease depends on the efficacy of vaccines in this younger age group. In a large, randomized, unblinded trial conducted in Finland, relatively low levels of antibody were induced after a series of three primary PRP-D immunizations at 3, 4, and 6 months of age. Despite these limited immunogenicity results, a high level of protective efficacy was shown during a 3-year period (protective efficacy of 87%, 95% confidence intervals 50% to 96%). Another trial, which was randomized, double blind, and placebo controlled, was conducted among 2113 Native Alaskan infants immunized (20 µg/0.5 mL) at 2, 4, and 6 months of age as part of their routine childhood immunizations. This population was chosen for the trial because it has the highest known incidence of invasive disease caused by H influenzae type b, and a trial in such a high-risk population could be conducted more carefully, with fewer study subjects, and in a shorter period of time. As in the Finnish trial, in this younger age group immune responses to PRP-D vaccine were meager, apparent only after the third dose of vaccine at 6 months of age.