title: Disease-enhancing antibodies improve the efficacy of bacterial toxin-neutralizing antibodies.
abstract: During infection, humoral immunity produces a polyclonal response with various immunoglobulins recognizing different epitopes within the microbe or toxin. Despite this diverse response, the biological activity of an antibody (Ab) is usually assessed by the action of a monoclonal population. We demonstrate that a combination of monoclonal antibodies (mAbs) that are individually disease enhancing or neutralizing to Bacillus anthracis protective antigen (PA), a component of anthrax toxin, results in significantly augmented protection against the toxin. This boosted protection is Fc gamma receptor (FcγR) dependent and involves the formation of stoichiometrically defined mAb-PA complexes that requires immunoglobulin bivalence and simultaneous interaction between PA and the two mAbs. The formation of these mAb-PA complexes inhibits PA oligomerization, resulting in protection. These data suggest that functional assessments of single Abs may inaccurately predict how the same Abs will operate in polyclonal preparations and imply that potentially therapeutic mAbs may be overlooked in single Ab screens.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Siu-Kei
authors.initials: SK
authors.lastname: Chow
authors.forename: Cameron
authors.initials: C
authors.lastname: Smith
authors.forename: Thomas
authors.initials: T
authors.lastname: MacCarthy
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Pohl
authors.forename: Aviv
authors.initials: A
authors.lastname: Bergman
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology; D019138:Antibodies, Blocking / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D005260:Female; D007136:Immunoglobulins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000907:Antibodies, Bacterial; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007136:Immunoglobulins; C030325:anthrax toxin