Disease-enhancing antibodies improve the efficacy of bacterial toxin-neutralizing antibodies

Siu Kei Chow, Cameron Smith, Thomas Maccarthy, Mary Ann Pohl, Aviv Bergman, Arturo Casadevall

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)417-428
Number of pages12
JournalCell Host and Microbe
Volume13
Issue number4
DOIs
StatePublished - Apr 17 2013

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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