Functional differences in idiotypically defined IgG1 anti-polysaccharide antibodies elicited by vaccination with Haemophilus influenzae type B polysaccharide-protein conjugates.
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.
Lucas
A H
AH
Children's Hospital Oakland Research Institute, CA 94609, USA.
Granoff
D M
DM
D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000276:immunology*; D000915:Antibody Affinity; D001770:Blood Bactericidal Activity; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007223:Infant; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D051381:Rats
D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D011135:Polysaccharides, Bacterial