Functional differences in idiotypically defined IgG1 anti- polysaccharide antibodies elicited by vaccination with Haemophilus influenzae type B polysaccharide-protein conjugates

• Published in: The Journal of immunology (1950) Vol. 154; no. 8; pp. 4195 - 4202
• Main Authors: Lucas, AH, Granoff, DM
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.04.1995
• Subjects: Animals; Animals, Newborn; Antibodies, Bacterial - immunology; Antibody Affinity; Blood Bactericidal Activity; Haemophilus Infections - prevention & control; Haemophilus influenzae; Haemophilus influenzae - immunology; Haemophilus Vaccines - immunology; Humans; Immunoglobulin G - immunology; Immunoglobulin Idiotypes - immunology; Infant; Polysaccharides, Bacterial - immunology; Rats
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.154.8.4195

We investigated the relationship between the form of the Haemophilus influenzae type B (Hib) polysaccharide (PS)-protein conjugate vaccine, Id expression, and Ab quality. Two post-vaccination pools were prepared from sera of infants vaccinated with either Hib PS oligomers coupled to CRM197, a mutant diphtheria toxin (HbOC), or with higher m.w. Hib PS coupled to an outer membrane protein complex of Neisseria meningitidis group B (Hib-OMP). The mean anti-Hib PS Ab avidity of the serum pool from the infants vaccinated with HbOC was threefold higher than that of the pool from infants vaccinated with Hib-OMP. Using sequential immunoabsorption, three IgG1 idiotypically-defined anti-Hib PS fractions were isolated from each of the serum pools: Hibld-1, Hibld-2, and a Hibld-1/-2-depleted population, designated Hibld-0. Hibld-1 and Hibld-2 are idiotypic markers for anti-Hib PS Abs expressing kappa II-A2 and lambda VII V regions, respectively. Hibld-1 anti-Hib PS Abs had significantly higher avidity, 2- to 19-fold higher in vitro bactericidal activity, and were more protective against Hib bacteremia in infant rats, than the respective Hibld-2 Abs isolated from each of the pools. Comparing the two vaccines, Hibld-1 anti-Hib PS Abs elicited by HbOC had significantly higher avidity and 10-fold higher bactericidal and rat protective activity than the Hibld-1 Abs elicited by Hib-OMP. These findings demonstrate that the molecular form of the Hib PS immunogen dictates both V region usage and quality of Ab function.