Passive protection against anthrax by using a high-affinity antitoxin antibody fragment lacking an Fc region.
Passive immunization has been successfully employed for protection against bacterial and viral infections for over 100 years. Immunoglobulin Fc regions play a critical role in the clearance of bacterial pathogens by mediating antibody-dependent and complement-dependent cytotoxicity. Here we show that antibody fragments engineered to recognize the protective antigen component of the B. anthracis exotoxin with high affinity and conjugated to polyethylene glycol (PEG) for prolonged circulation half-life confer significant protection against inhalation anthrax despite their lack of Fc regions. The speed and lower manufacturing cost of bacterially expressed PEGylated antibody fragments could provide decisive advantages for anthrax prophylaxis. Importantly, our results suggest that PEGylated antibody fragments may represent a unique approach for mounting a rapid therapeutic response to emerging pathogen infections.
Mabry
Robert
R
Department of Chemical Engineering and Biomedical Engineering, University of Texas at Austin, 1 University Station, Austin, TX 78712, USA.
Rani
Mridula
M
Geiger
Robert
R
Hubbard
Gene B
GB
Carrion
Ricardo
R
Brasky
Kathleen
K
Patterson
Jean L
JL
Georgiou
George
G
Iverson
B L
BL
D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000915:Antibody Affinity; D000942:Antigens, Bacterial / Q000276:immunology*; D000992:Antitoxins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D007116:Immunization, Passive; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D014115:Toxemia / Q000517:prevention & control
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; C030325:anthrax toxin; D011092:Polyethylene Glycols