Monoclonal antibodies targeting different cell wall antigens of group B streptococcus mediate protection in both Fc-dependent and independent manner

Abstract

Group B streptococcus remains an important neonatal pathogen in spite of widely adopted intrapartum antibiotic administration; therefore immune prophylaxis for GBS infections is highly warranted. In passive immunization and lethal challenge studies with multiple GBS strains, we characterized the protective effect of rabbit polyclonal and murine monoclonal antibodies specific for four multi-functional cell wall anchored proteins, FbsA, BibA, PilA and PilB. Single specificity rabbit sera or mAbs induced high level, but strain dependent protection, while their combinations resulted in superior and broad efficacy against all GBS strains tested. Polyclonal and monoclonal antibodies specific for the pilus proteins exerted very potent opsonophagocytic killing activity in vitro and required the Fc domain for protection in vivo. In contrast, FbsA and BibA specific antibodies failed to show OPK activity, but their Fab fragments fully protected animals, suggesting that blocking the function of these proteins was the major mode of action. These data are supportive for developing immune prophylaxis with human mAbs for prematurely born neonates who receive low levels of antibodies by maternofetal transport and are characterized by not fully developed phagocytic and complement activity.