Selection of human antibodies against cell surface-associated oligomeric anthrax protective antigen.

Abstract:

:The protective antigen (PA(83)) of Bacillus anthracis is the dominant antigen in natural and vaccine-induced immunity to anthrax infection. Three human single-chain variable fragments (scFvs) against cell bound PA were isolated from an antibody phage display library. Specifically, the antibodies were evaluated for their ability to bind to cell bound heptameric PA and ultimately protect against the cytotoxicity of lethal toxin. In total, all three scFvs possessed neutralizing activity against the cytotoxic effects of lethal toxin in a macrophage lysis assay. The K(d) values of the Fabs were determined, interestingly their protective effects did not parallel their affinities; hence, a simple binding argument alone to PA(63) cannot be used as the distinguishing feature for the prediction of their neutralization abilities. Immunofluorescent microscopy experiments were conducted and provided strong evidence for Fab binding to oligomeric PA on the cell surface and thus a plausible mechanism for the toxin neutralization activity that was observed. The results of this study presented herein suggest that our antibodies compete with LF-PA cell surface interactions, and thus may provide potential application of human antibodies as passive immunization prophylactics in cases of B. anthracis exposure and infection.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Steiniger SC,Altobell LJ 3rd,Zhou B,Janda KD

doi

10.1016/j.molimm.2006.11.011

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

2749-55

issue

10

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(06)00669-9

journal_volume

44

pub_type

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