Development of Anti-Toxins Antibodies for Biodefense

Pelat, Thibaut; Avril, Arnaud

doi:10.4172/2157-2526.s2-005

Cited by 3 publications

(2 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the construction of immune libraries, human volunteers may be substituted by non-human primates. in particular, it was demonstrated that macaque antibodies are close to their human counterparts, which might suggest a good tolerance in therapy [ 16 , 17 ]. Non-human primate immunizations allow generation of immune gene-libraries focused on the antigen, from which high-affinity antibodies can be isolated.…”

Section: Introductionmentioning

confidence: 99%

Isolation of nanomolar scFvs of non-human primate origin, cross-neutralizing botulinum neurotoxins A1 and A2 by targeting their heavy chain

Avril¹,

Miethe

Popoff

et al. 2015

BMC Biotechnol

Self Cite

View full text Add to dashboard Cite

BackgroundBotulism is a naturally occurring disease, mainly caused by the ingestion of food contaminated by the botulinum neurotoxins (BoNTs). Botulinum neurotoxins are the most lethal. They are classified among the six major biological warfare agents by the Centers for Disease Control. BoNTs act on the cholinergic motoneurons, where they cleave proteins implicated in acetylcholine vesicle exocytosis. This exocytosis inhibition induces a flaccid paralysis progressively affecting all the muscles and generally engendering a respiratory distress. BoNTs are also utilized in medicine, mainly for the treatment of neuromuscular disorders, preventing large scale vaccination. Botulism specific treatment requires injections of antitoxins, usually of equine origin and thus poorly tolerated. Therefore, development of human or human-like neutralizing antibodies is of a major interest, and it is the subject of the European framework project called “AntiBotABE”.ResultsIn this study, starting from a macaque immunized with the recombinant heavy chain of BoNT/A1 (BoNT/A1-HC), an immune antibody phage-display library was generated and antibody fragments (single chain Fragment variable) with nanomolar affinity were isolated and further characterized. The neutralization capacities of these scFvs were analyzed in the mouse phrenic nerve-hemidiaphragm assay.ConclusionsAfter a three-round panning, 24 antibody fragments with affinity better than 10 nM were isolated. Three of them neutralized BoNT/A1 efficiently and two cross-neutralized BoNT/A1 and BoNT/A2 subtypes in the mouse phrenic nerve-hemidiaphragm assay. These are the first monoclonal human-like antibodies cross-neutralizing both BoNT/A1 and BoNT/A2. The antibody A1HC38 was selected for further development, and could be clinically developed for the prophylaxis and treatment of botulism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12896-015-0206-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Isolation of nanomolar scFvs of non-human primate origin, cross-neutralizing botulinum neurotoxins A1 and A2 by targeting their heavy chain

Avril¹,

Miethe

Popoff

et al. 2015

BMC Biotechnol

Self Cite

View full text Add to dashboard Cite

show abstract

“…The mechanism of ricin entry into the cell and its intracellular transport involves a number of steps that are well documented (see [4,[10][11][12][13] and references therein). Mature ricin is a dimeric cytotoxin.…”

Section: Introductionmentioning

confidence: 99%

Modeling of toxin–antibody interaction and toxin transport toward the endoplasmic reticulum

Skakauskas

Katauskis

2015

J Biol Phys

View full text Add to dashboard Cite

A model for toxin-antibody interaction and toxin trafficking towards the endoplasmic-reticulum is presented. Antibody and toxin (ricin) initially are delivered outside the cell. The model involves: the pinocytotic (cellular drinking) and receptor-mediated toxin internalization modes from the extracellular into the intracellular domain, its exocytotic excretion from the cytosol back to the extracellular medium, the intact toxin retrograde transport to the endoplasmic reticulum, the anterograde toxin movement outward from the cell across the plasma membrane, the lysosomal toxin degradation, and the toxin clearance (removal from the system) flux. The model consists of a set of coupled PDEs. Using an averaging procedure, the model is reduced to a system of coupled ODEs. Both PDEs and ODEs systems are solved numerically. Numerical results are illustrated by figures and discussed.

show abstract