DIFFERING USE OF NEUTROPHIL (PMN) RECEPTORS BY IMMUNOGLOBULIN G (IgG) ELICITED IN RESPONSE TO GROUP B STREPTOCOCCAL (GBS) TYPE III POLYSACCHARIDE(III-PS) OR GBS III-PS TETANUS TOXOID (III-TT) CONJUGATE VACCINES.

Abstract

Previously, we have shown an interactive effect for PMN Fc and complement receptors (CR) in phagocytosis of type III GBS. We proposed that antibodies elicited to GBS III-PS or III-TT vaccines might differ in PMN receptor use. Sera from 10 adults with low preimmunization levels of III GBS-specific antibody (<1.0 μg/ml, IgG ELISA) were collected 1 yr after receipt of III-PS or III-TT vaccines when antibody levels were 7-213 μg/ml. The lowest concentration of purified IgG that would support 90% killing of III GBS in an opsonophagocytic (OP) assay, 0.7 μg/ml of antibody to III GBS, was used in further testing of IgG from each of the individual vaccinees. Blockade of CR3 by the monoclonal antibody (mAb) Leu 15 significantly inhibited OP mediated by IgG from III-PS recipients but not for III-TT recipients (83.3 ± 21.8% vs 35 ± 10.1%, P = 0.009, unpaired t test). Neither showed significant inhibition by mAb CD35, directed against CR1. In contrast, uptake of radiolabeled type III GBS was significantly impaired for IgG from III-TT but not for that from III-PS recipients when FcRII was blocked using Fab fragments of mAb IV.3 (74.0 ± 16.5% vs 16.2 ± 19.0% inhibition, P = 0.002) or when FcRIII was blocked by Fab′2 fragments of mAb 3G8 (45.5± 14.3% vs 7.9 ± 9.4% inhibition, P = 0.003). There was no difference in the IgG subclass responses to type III GBS-PS whether it was conjugated to TT or not; IgG2 predominated for both groups. These results indicate reduced use of CR3 and increased use of FcR for IgG elicited in response to III-TT when compared to IgG from III-PS recipients. Differing use of PMN FcR or CR by IgG elicited in response to III-PS vs III-TT hasimplications important for host defense.