Clinical experience with Haemophilus influenzae type b conjugate vaccines

The importance of Haemophilus influenzae type b as the main cause of serious bacteremic infections in young children and the consequent need for preventive measures have been widely appreciated since the 1970s. The knowledge that serum antibodies to the polysaccharide capsule of H influenzae type b increase with age and correlate with resistance to this infection encouraged work toward a vaccine based on the H influenzae type b polysaccharide. Such a vaccine was used in 1974 in a field trial in Finland. Two important lessons were learned. First, vaccine-induced antibodies to the polyribosylribitol-phosphate (PRP) polysaccharide correlated with protection from disease caused by H influenzae type b, so that the serum anti-PRP concentration predicting protection could be estimated as 1 microgram/mL. Second, the vaccine was not effective in infancy; protection and serum antibody concentrations above 1 microgram/mL were not observed before 18 to 24 months of age. The poor immunogenicity of PRP in infancy has been observed in a large number of studies and is shared by other bacterial polysaccharides. Although the reason for this is not known, the most likely hypothesis associates poor immunizing ability in infancy with the "T-independent" nature of these polysaccharide antigens. Such antigens would be unable to stimulate T lymphocytes; therefore, immunity to them would depend exclusively on B cells and antibodies produced by them. If infants, by and large, lack B cells that could be stimulated directly by a polysaccharide antigen, they cannot respond to the polysaccharide vaccine. This hypothesis immediately suggests possibilities for improvement of the vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)