Oligosaccharide-protein conjugate vaccines induce and prime for oligoclonal IgG antibody responses to the Haemophilus influenzae b capsular polysaccharide in human infants

Abstract

The diversity of the IgG antibody induced by immunization of human infants and children with conjugate vaccines, composed of oligosaccharides prepared from the Haemophilus influenzae b capsular polysaccharide (CP) and covalently linked to diphtheria toxoids, was studied by analytical IEF. The antibody response was similar, in the degree of restriction, to that observed in the antibody response of older children to immunization with the CP alone. The booster responses induced by reimmunization with conjugate vaccines were accompanied by increases predominantly in the IgG antibody clonotypes expressed after the priming dose of vaccine. After a series of conjugate immunizations, immunization with isolated CP boosted the antibody titer and increased expression from all the clonotypes that were expressed after conjugate immunization. These findings suggest that the conjugate vaccines are acting on a limited number of human B cell clones that are preferentially restimulated after reimmunization. Little evidence of antigen-specific B cell recruitment was found. In addition, the ability of isolated CP immunization to restimulate the same B cell clone indicates that the responding B cell has matured and suggests a linear rather than a dual developmental pathway for the B cell participating in this human antibody response.