Prevention of invasive Haemophilus influenzae type b disease: lessons from vaccine efficacy trials.

To assess vaccines, multiple laboratory investigations and immunogenicity studies are conducted but the ultimate tests of the effectiveness of a vaccine are field trials that evaluate disease prevention. Immunogenicity studies are often used as a surrogate for protection, but it is often difficult to determine precisely the level of antibody needed for protection and it is not always clear what immunologic factors most determine protection. However, efficacy trials are difficult to conduct well and there are only a limited number of ways to perform such studies. Nonetheless, the results of efficacy studies are essential for the appropriate selection of the best Hib vaccines and to establish recommendations for optimal use. The first Hib vaccine, the PRP (polyribosylribitol phosphate) polysaccharide vaccine, was shown by several efficacy studies to have no protective efficacy in young infants, and to have only limited, if any, efficacy in older children. The first Hib polysaccharide conjugate vaccine, PRP-D, is more immunogenic and provides better protection than PRP in older children (greater than 18 months of age), but it has limitations in both immunogenicity and protective efficacy when given to children younger than 6 months of age. Newer, more promising, Hib conjugate vaccines are now available, and include HbOC, PRP-OMP, and PRP-T vaccines. Each is currently being evaluated in field trials to evaluate protective efficacy and the methods and results of these trials will be reviewed. The control of invasive Hib disease worldwide will depend upon the appropriate application of knowledge derived from these field trials.