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Volume 5, Issue 6(Suppl) J Infect Dis Ther, an open access journal
ISSN: 2332-0877 Euro Infectious Diseases 2017
September 07-09, 2017
September 07-09, 2017 | Paris, France
Infectious Diseases
6th Euro-Global Conference on
Development of five hyper-humanized antibodies neutralizing the Botulinum neurotoxins A, B and E: The
European AntiBotABE project
Arnaud Avril1, Sebastian Miethe2, Michel R Popoff3, Christelle Mazuet 3, Christine Rasetti-escargueil4, Hannu Korkeala5, Dorothea Sesardic4, Thibaut Pelat6, and
Michael Hust2
1Institut de Recherche Biomédicale des Armées, France
2Technische Universität Braunschweig, Germany
3Unit of Anaerobic Bacteria and Toxins and National Reference Center of Anaerobic Bacteria and Botulism, Paris, France
4National Institute for Biological Standards and Control, United Kingdom
5University of Helsinki, Finland
6Biotem, France
Botulism is a naturally occurring disease, mainly caused by the ingestion of food contaminated by one of the 7 serotypes (A to G) of
botulinum neurotoxins (BoNTs). BoNT/A is the most lethal biological substance currently known, with a human 50% lethal dose
estimated at 1 -1, and they are classified among the 6 major biological warfare agents. AntiBotABE, a European Framework, 7
funded projects aimed to develop 6 humanized IgGs, neutralizing BoNT serotypes A, B and E by targeting their heavy (HC) and light
chains (LC). Six macaques were immunized with the recombinant LC or HC of BoNT/A, B or E, and their corresponding immune
libraries were generated and screened by phage-display. After each panning, the most reactive scFv were isolated and their affinity
measured. Inhibition or neutralization capacities were determined in vitro (SNAP25 or VAMP2 endopeptidasic assay) or ex vivo
(mouse phrenic nerve-diaphragm assay). Neutralizing scFvs were identified for 5 of the 6 antigens. For each of the 5 libraries, the
most efficient scFv was germline-humanized and expressed as full-length IgG. In the mouse bioassays, 3/5 IgGs alone and all IgGs
in pairs, protected mice from paralysis or death after a challenge with the respective BoNT serotype. 1–5 Antibodies isolated during
this project are potential lead candidates for further clinical development and we are looking for clinical development opportunity.
Biography
Arnaud Avril works for the French Armed Forces Biomedical Research Institute (IRBA), based in Paris area. He has a Master degree in Genetic and Immunology
from Lyon University (France) and a PhD in Biotechnology applied to antibodies from the Grenoble-Alpes University (France). He is the Head of a team specialized
in the research, development and engineering of recombinant antibodies against rare diseases for biodefense. He has developed germline-humanized recombinant
antibodies starting from non-human primates immunized with non-toxic antigens. He has contributed to the development of several antibodies neutralizing botulinum
neurotoxins, anthrax, ricin and Orthopoxvirus. He has also contributed to the development immuno-diagnostic assays for the rapid, convenient and cheap detection
of biological agents, for armed forces, medical staff and first responders. He is involved as an expert on the clinical development of a recombinant antibody for
anthrax therapy.
Arnaud Avril et al., J Infect Dis Ther 2017, 5:6(Suppl)
DOI: 10.4172/2332-0877-C1-032