Abstract
The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC) of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies). For antibody isolation, macaques were immunized with the recombinant and non-toxic BoNT/A, B or E, HC or LC, followed by the generation of immune phage-display libraries. Antibodies were selected from these libraries against the holotoxin and further analyzed in in vitro and ex vivo assays. For each library, the best ex vivo neutralizing antibody fragments were germline-humanized and expressed as immunoglobulin G (IgGs). The IgGs were tested in vivo, in a standardized model of protection, and challenged with toxins obtained from collections of Clostridium strains. Protective antibody combinations against BoNT/A and BoNT/B were evidenced and for BoNT/E, the anti-LC antibody alone was found highly protective. The combination of these five antibodies as an oligoclonal antibody cocktail can be clinically and regulatorily developed while their high “humanness” predicts a high tolerance in humans.
Highlights
The aim of the AntiBotABE Program was to develop recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E, responsible for most human botulism cases
We describe the results of the European framework project AntiBotABE
We reported the generation of neutralizing single chain Fragment variables (scFvs) and scFv-Fc derived from macaques against BoNT/A, BoNT/B and BoNT/E: SEM120-IIIC1, A1HC38, BLC3, B2-7 and ELC18
Summary
The aim of the AntiBotABE Program was to develop recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E, responsible for most human botulism cases. The heavy and light chains (HC and LC) of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies). Our strategy used macaque immune libraries to develop neutralizing/protective antibodies and was successfully applied in former projects against ricin [1], the lethal toxin of anthrax [2,3], Venezualan equine encephalits virus [4], Western equine encephelatis virus [5] and Marburg virus [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
