Laboratory correlates of protection against Haemophilus influenzae type b disease. Importance of assessment of antibody avidity and immunologic memory.

The concentration of serum antibody to the Haemophilus influenzae type b polysaccharide sufficient to confer protection against Hib disease has been estimated to range from 0.15 to 1.0 microgram/ml as measured by conventional antigen binding assays. However, the ability of these serologic tests to predict vaccine equivalence and/or protective efficacy is limited since there are important qualitative differences in vaccine-induced anti-PRP antibody, such as isotype, variable region usage, and antibody avidity. These differences may profoundly affect the biologic activity of the antibody. Also, Hib conjugate vaccination primes infants for memory antibody responses to a subsequent encounter with PRP, and immunologic priming can occur in infants with very low serum anti-PRP antibody responses to conjugate vaccination, or in those whose antibody concentrations have declined after vaccination. Primed infants are likely to be protected against Hib disease in the absence of "protective" serum antibody concentrations because priming permits a rapid serum anti-PRP antibody response upon encountering the organism. Thus, quantitative assessment of immunogenicity, by itself, is insufficient to predict vaccine equivalence or protective efficacy. In defining surrogate serologic tests for prediction of vaccine efficacy, assessments of antibody avidity and induction of immunologic memory should be included. Ideally, these assessments should be supplemented with antibody functional assays such as complement-mediated bactericidal activity, opsonic activity, or passive protection in animal models of disease.