Nature Biotechnology
20, 597 - 601 (2002)
doi:10.1038/nbt0602-597
Protection against anthrax toxin by recombinant antibody fragments
correlates with antigen affinityJennifer A. Maynard1, 2, 6, Catharina B.M. Maassen2, Stephen H. Leppla3, Kathleen Brasky4, Jean L. Patterson4, Brent L. Iverson2, 5
& George Georgiou1, 2, 61
Department of Chemical Engineering, University of
Texas, Austin, TX 78712. 2
Institute for Cellular and Molecular Biology,
University of Texas, Austin, TX
78712. 3
National Institute of Dental and Craniofacial
Research, National Institutes of Health, Bethesda, MD
20892. 4
Southwest Foundation for Biological
Research, San Antonio, TX 78227. 5
Department of Chemistry and Biochemistry,
University of Texas, Austin, TX
78712. 6
Department of Biomedical Engineering, University
of Texas, Austin, TX 78712.
Correspondence should be addressed to George Georgiou gg@che.utexas.eduThe tripartite toxin produced by Bacillus anthracis is the
key determinant in the etiology of anthrax. We have engineered a panel of
toxin-neutralizing antibodies, including single-chain variable fragments
(scFvs) and scFvs fused to a human constant  domain (scAbs), that bind
to the protective antigen subunit of the toxin with equilibrium dissociation
constants (K
d) between 63 nM and 0.25 nM. The entire antibody
panel showed high serum, thermal, and denaturant stability. In vitro,
post-challenge protection of macrophages from the action of the holotoxin
correlated with the K
d of the scFv variants. Strong
correlations among antibody construct affinity, serum half-life, and protection
were also observed in a rat model of toxin challenge. High-affinity
toxin-neutralizing antibodies may be of therapeutic value for alleviating the
symptoms of anthrax toxin in infected individuals and for medium-term
prophylaxis to infection.
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