Prospects for prevention of Haemophilus influenzae type b disease by immunization

Abstract

A vaccine consisting of the polysaccharide (PS) capsule of Haemophilus influenzae type b (Hib) has recently been licensed in the United States. This vaccine is safe and effective in preventing invasive Hib disease in children two years of age and older, but it is ineffective in younger children, the group at greatest risk of disease. The PS vaccine also may be ineffective in preventing disease in certain subgroups of the population that are genetically at increased risk of disease and show impaired antibody responses to immunization. Thus, new strategies need to be considered. Currently, several new Hib PS-protein conjugate vaccines are being evaluated. These vaccines differ in their method of preparation, carrier protein, and PS size. In contrast to the plain Hib PS vaccine, conjugate vaccines are immunogenic in infants and elicit boostable increases in antibody to PS upon reinjection of vaccine. However, some infants less than six months of age do not respond. To confer protection on all infants, it may be necessary to modify further the conjugate vaccines. One approach is to use outer membrane proteins (OMPs) as vaccine components. Five major OMPs have been purified from Hib, and three, P1 (50 kilodalton [kDa]), P2 (37 kDa), and P6 (16 kDa), contain antigens capable of eliciting strain-specific protective antibodies in experimental animals. In summary, PS-protein conjugate vaccines hold enormous promise for the prevention of Hib disease in infants, but further work is needed to define the optimal carrier protein, PS size, and method of coupling. Information is also needed on whether genetic factors influence responses to these vaccines.