The biology of Haemophilus influenzae type b vaccination failure

Abstract

Vaccination with unconjugated polysaccharide vaccine against Haemophilus influenzae type b (Hib) disease at a median age of 25 months was not effective in a group of children who developed Hib disease at a median age of 35 months. This group had normal serum immunoglobulin concentrations but impaired anticapsular antibody responses to Hib infection and to reimmunization with unconjugated polysaccharide. Another group vaccinated with conjugated polysaccharide vaccine at a median age of 18 months developed Hib disease at a median age of 24 months. Of this group, 40% had subnormal immunoglobulin concentrations, particularly IgG2, and showed impaired antibody responses to Hib infection, whereas those with normal immunoglobulin concentrations showed high antibody responses to Hib infection. In both vaccination failure groups, low antibody responders to infection responded to revaccination with Hib conjugate, and most children expressed the idiotype HibId-1 in convalescent or postrevaccination sera. The presence of this idiotype implies that vaccination failure did not result from an inability to use the V kappa II A2 variable region gene, which is used in the anticapsular antibody response of most healthy children.