Avidity and Bactericidal Activity of Antibody Elicited by Different Haemophilus influenzae Type b Conjugate Vaccines

Abstract

Objective. —Antibody avidity is a measure of the functional affinity of serum antibody to bind to antigen. In this study, we compared the avidity of antibodies elicited by vaccination with threeHaemophilus influenzaetype b (Hib) conjugate vaccines and investigated the relationship between antibody avidity and the ability of antibody to activate complement-mediated bactericidal activity. Design. —A convenience sample of 171 postvaccination serum samples with more than 0.5 μg/mL of anticapsular antibody, the minimum concentration required for measurement of avidity. The serum samples were obtained from infants participating in immunogenicity trials with Hib capsular polysaccharide (PRP) conjugated to meningococcal outer membrane protein complex (PRP-OMPC) or to tetanus toxoid (PRP-T), or PRP oligomers conjugated to a nontoxic mutant diphtheria toxin, CRM₁₉₇(Oligo-CRM). Patients. —Healthy infants recruited in private practices. Primary Outcome Measures. —Avidity of vaccine-induced serum anticapsular antibody and serum bactericidal titers. Results. —In infants vaccinated at 2, 4, and 6 months of age, Oligo-CRM evoked antibody of higher avidity than PRP-OMPC (P<.001). The mean avidity of antibody elicited by PRP-T was intermediate, being lower than Oligo-CRM (P<.02) but higher than PRP-OMPC (P=.001). Also, after one dose, 18-month-old infants given Oligo-CRM had higher avidity antibodies compared with those given PRP-OMPC (P<.001). Half of the infants in both age groups who were given Oligo-CRM developed antibody avidity of 2.50 nM^-1or greater, whereas more than two thirds of the infants given PRP-OMPC had avidity values of 1.25 nM^-1or less. Antibodies with avidity of 1.25 nM^-1or less were, on average, 6.6-fold less active in assays of complement-mediated bactericidal activity than antibodies with avidity of 2.50 nM^-1or greater (P<.001). Conclusions. —Oligo-CRM and PRP-T conjugate vaccines elicit higher avidity antibody than PRP-OMPC, and high-avidity antibody is more potent than low-avidity antibody in serum bactericidal assays. Consideration should be given to including measurement of antibody avidity in assessment of new vaccines since avidity may affect the ability of serum antibody to confer protection against disease. (JAMA. 1992;267:1489-1494)