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PMID: 16299334 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Passive protection against anthrax by using a high-affinity antitoxin antibody fragment lacking an Fc region.

Infection and immunity ·Vol. 73 ·No. 12 ·2005-12-00 ·Pages 8362-8

Mabry R, Rani M, Geiger R, Hubbard GB, Carrion R, Brasky K, Patterson JL, Georgiou G, Iverson BL

Abstract

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.

MeSH Terms
Animals Anthrax/prevention & control Antibodies, Bacterial/administration & dosage,chemistry,therapeutic use Antibody Affinity Antigens, Bacterial/immunology Antitoxins/administration & dosage,chemistry,therapeutic use Bacillus anthracis/immunology Bacterial Toxins/immunology Female Guinea Pigs Immunization, Passive Immunoglobulin Fc Fragments/immunology Immunoglobulin Fragments/administration & dosage,chemistry,therapeutic use Immunoglobulin Variable Region/administration & dosage,chemistry,therapeutic use Polyethylene Glycols/administration & dosage,chemistry,therapeutic use Toxemia/prevention & control
Chemicals
Antibodies, Bacterial Antigens, Bacterial Antitoxins Bacterial Toxins Immunoglobulin Fc Fragments Immunoglobulin Fragments Immunoglobulin Variable Region anthrax toxin Polyethylene Glycols
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Mabry Robert
Department of Chemical Engineering and Biomedical Engineering, University of Texas at Austin, 1 University Station, Austin, TX 78712, USA.
Rani Mridula
Geiger Robert
Hubbard Gene B
Carrion Ricardo
Brasky Kathleen
Patterson Jean L
Georgiou George
Iverson B L
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.73.12.8362-8368.2005
Published
2005-12-00
Pages
8362-8
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC1307075
Subset
IM
Grants
NIAID NIH HHS · U01 AI056431 · United States
NIAID NIH HHS · U01 AI56431 · United States
External Links
PubMed source DOI: 10.1128/IAI.73.12.8362-8368.2005 PMC Full Text View journal details
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