@article{5f7762de6b0a4235abefae425a934467,
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.",
author = "Chow, {Siu Kei} and Cameron Smith and Thomas Maccarthy and Pohl, {Mary Ann} and Aviv Bergman and Arturo Casadevall",
note = "Funding Information: We thank Hamlet Chu, Rafael Prados-Rosales, and Ka Wing Wong for useful comments, and Susan Buhl and Manxia Fan at the Hybridoma Facility, Scott Garforth and Albe Man Kid Chan at the Macromolecular Therapeutics Development Core, Jinghang Zhang at the Flow Cytometry Core Facility, and Huiyong Cheng at Department of Biochemistry and Carolina Coelho at Department of Microbiology and Immunology, at AECOM, for technical support. This work was supported by grants from the Department of Defense (proposal log #07164001; Award Number W81XWH08-01-0011), from the Northeast Biodefense Center (5U54AI05715807 to Lipkin, W.I.). In addition, A.C. is also supported by HL059842-3, A1033774, A1052733, and AI033142. S.-K.C. and A.C. designed the biological experiments, interpreted the results, produced the figures, and wrote the paper. S.-K.C. performed all the biological experiments. M.A.P. carried out the antibody sequencing and analyzed the results. C.S., T.M., and A.B. designed and performed the rule-based modeling, interpreted the results, produced the figures, and wrote the paper. ",
year = "2013",
month = apr,
day = "17",
doi = "10.1016/j.chom.2013.03.001",
language = "English (US)",
volume = "13",
pages = "417--428",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "4",
}