Bactericidal and opsonic activity of IgG1 and IgG2 anticapsular antibodies to Haemophilus influenzae type b

Complement-mediated bactericidal and opsonic activity of IgG1 and IgG2 antibodies to Haemophilus influenzae type b polysaccharide (polyribosyl ribitol phosphate [PRP]) were investigated. The antibody sources were IgG1 or IgG2 subclass polyclonal antibody fractions prepared by immunoabsorption of sera from adults immunized with PRP or PRP-diphtheria toxoid conjugate vaccine or clonally purified anti-PRP antibodies from eight adults immunized with PRP vaccine. In bactericidal assays using an inoculum of 3 x 10(3) colony-forming units (cfu)/ml, twofold lower concentrations of IgG1 compared with IgG2 antibody were required for 50% killing. With approximately 10(6) cfu/ml, IgG1 antibody killed 3 logs more of bacteria than were killed by comparable concentrations of IgG2 antibody. The IgG1 antibody also required lower concentrations of complement than did the IgG2 antibody for comparable bacteriolytic activity. Clonally purified IgG1 and IgG2 anti-PRP antibodies from most individuals showed similar relative differences in bactericidal activity. IgG1 anti-PRP antibody was also more efficient than IgG2 anti-PRP antibody in enhancing the uptake of radiolabeled type b H. influenzae by human polymorphonuclear leukocytes in the presence of complement and in protecting infant rats from developing bacteremia. However, the differences in opsonic or protective activity of the two subclasses were smaller than the differences in bactericidal activity. Thus, IgG1 anti-PRP antibody is functionally more effective than IgG2 antibody, but it is likely that both subclasses can confer protection against disease.