Neutralizing monoclonal antibody against anthrax lethal factor inhibits intoxication in a mouse model.
Anthrax toxin is the dominant virulence factor of Bacillus anthracis; drugs blocking its action could therefore have therapeutic benefit. We report here the production of a neutralizing monoclonal antibody (mAb) against anthrax lethal factor (LF) and the inhibition by the antibody of anthrax lethal toxin (LeTx) formation. The anti-LF monoclonal antibody LF8 neutralized the LeTx challenge both in vitro with macrophage J774A.1 cells and in vivo in nude mice. Our data suggested that LF8 binds LF at or near the PA binding domain. A set of dodecameric peptides was selected from a phage-displayed peptide library through their specific binding to anti-LF neutralizing mAb LF8. These small peptides compete with LF to bind LF8. Further investigation is undergoing to test the potential application of these peptides to the clinical treatment of anthrax infection by blocking LeTx formation.
Zhao
Ping
P
Laboratory of Antibody Technology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Liang
Xudong
X
Kalbfleisch
Jessica
J
Koo
Han-Mo
HM
Cao
Brian
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000633:toxicity; D002460:Cell Line; D018604:Epitope Mapping; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009500:Neutralization Tests; D019151:Peptide Library; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002352:Carrier Proteins; D019151:Peptide Library; C030325:anthrax toxin