NDLI: Characterization of Botulinum Neurotoxin Type A Neutralizing Monoclonal Antibodies and Influence of Their Half-Lives on Therapeutic Activity

Content Provider	PubMed Central
Author	Mazuet, Christelle Dano, Julie Popoff, Michel R. Christophe, Créminon Volland, Hervé
Editor	Bruggemann, Holger
Abstract	Botulinum toxins, i.e. BoNT/A to/G, include the most toxic substances known. Since botulism is a potentially fatal neuroparalytic disease with possible use as a biowarfare weapon (Centers for Disease Control and Prevention category A bioterrorism agent), intensive efforts are being made to develop vaccines or neutralizing antibodies. The use of active fragments from non-human immunoglobulins (F(ab')2, Fab', scFv), chemically modified or not, may avoid side effects, but also largely modify the in vivo half-life and effectiveness of these reagents. We evaluated the neutralizing activity of several monoclonal anti-BoNT/A antibodies (mAbs). F(ab')2 fragments, native or treated with polyethyleneglycol (PEG), were prepared from selected mAbs to determine their half-life and neutralizing activity as compared with the initial mAbs. We compared the protective efficiency of the different biochemical forms of anti-toxin mAbs providing the same neutralizing activity. Among fourteen tested mAbs, twelve exhibited neutralizing activity. Fragments from two of the best mAbs (TA12 and TA17), recognizing different epitopes, were produced. These two mAbs neutralized the A1 subtype of the toxin more efficiently than the A2 or A3 subtypes. Since mAb TA12 and its fragments both exhibited the greatest neutralizing activity, they were further evaluated in the therapeutic experiments. These showed that, in a mouse model, a 2- to 4-h interval between toxin and antitoxin injection allows the treatment to remain effective, but also suggested an absence of correlation between the half-life of the antitoxins and the length of time before treatment after botulinum toxin A contamination. These experiments demonstrate that PEG treatment has a strong impact on the half-life of the fragments, without affecting the effectiveness of neutralization, which was maintained after preparation of the fragments. These reagents may be useful for rapid treatment after botulinum toxin A contamination.
Related Links	http://dx.doi.org/10.1371/journal.pone.0012416
Starting Page	12416
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	8
Volume Number	5
Language	English
Publisher	Public Library of Science
Publisher Date	2010-08-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity

Characterization of a highly neutralizing single monoclonal antibody to botulinum neurotoxin type A

Epitope Characterization and Variable Region Sequence of F1-40, a High-Affinity Monoclonal Antibody to Botulinum Neurotoxin Type A (Hall Strain)

Correction: Epitope Characterization and Variable Region Sequence of F1-40, a High-Affinity Monoclonal Antibody to Botulinum Neurotoxin Type A (Hall Strain)

Correction: Epitope Characterization and Variable Region Sequence of F1-40, a High-Affinity Monoclonal Antibody to Botulinum Neurotoxin Type A (Hall Strain)

Correction: Epitope Characterization and Variable Region Sequence of F1-40, a High-Affinity Monoclonal Antibody to Botulinum Neurotoxin Type A (Hall Strain)

Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H

Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B

Conjugative Botulinum Neurotoxin-Encoding Plasmids in Clostridium botulinum

Characterization of Botulinum Neurotoxin Type A Neutralizing Monoclonal Antibodies and Influence of Their Half-Lives on Therapeutic Activity

Similar Documents

Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity

Characterization of a highly neutralizing single monoclonal antibody to botulinum neurotoxin type A

Epitope Characterization and Variable Region Sequence of F1-40, a High-Affinity Monoclonal Antibody to Botulinum Neurotoxin Type A (Hall Strain)

Correction: Epitope Characterization and Variable Region Sequence of F1-40, a High-Affinity Monoclonal Antibody to Botulinum Neurotoxin Type A (Hall Strain)

Correction: Epitope Characterization and Variable Region Sequence of F1-40, a High-Affinity Monoclonal Antibody to Botulinum Neurotoxin Type A (Hall Strain)

Correction: Epitope Characterization and Variable Region Sequence of F1-40, a High-Affinity Monoclonal Antibody to Botulinum Neurotoxin Type A (Hall Strain)

Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H

Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B

Conjugative Botulinum Neurotoxin-Encoding Plasmids in Clostridium botulinum

Characterization of Botulinum Neurotoxin Type A Neutralizing Monoclonal Antibodies and Influence of Their Half-Lives on Therapeutic Activity