Antivenom is an antibody product that neutralizes a particular venom’s toxins. Venoms contain a complex mixture of hundreds of substances. Typically, an animal, such as a horse or goat, is injected with a small amount of venom. The antibodies released by the animal’s immune system are then harvested through blood collection. The blood serum or plasma is then concentrated and purified into pharmaceutical-grade anti-venom. Such antivenin can cause a series of severe side effects due to the heterogeneity and a high degree of immunogenicity.
Challenge:
The challenge was to improve the efficiency of antivenom production. As generating therapeutic horse sera is labor intensive and produces inconsistent antivenom with poor thermal stability, the antibody developed needed to be consistent in production methods, thermally stable, and broad enough to target clinically-relevant toxins but specific enough to prevent side effects.
Solution:
To improve the efficiency of antivenom production, we utilized llamas that contain conventional antibodies as well as heavy chain-only antibodies. To develop these single domain antibodies, we optimized immunization protocols and used phage display technology to select for antibody binders, by constructing a phagemid library and panning it using an individual recombinant toxin.
This resulted in single domain antibodies of approximately 15kDa that were immune-reactive to the panned toxin. These recombinant single domain antibodies reduce the inconsistencies of relying on horse sera, as once developed, the antibodies are readily reproducible within the lab. Single domain antibodies have unique properties in homogeneity and specificity, which can decrease the chances of anaphylaxis. In addition, the single domain antibodies are highly stable, easy to produce, very stable over a broad range of temperatures and pH conditions, permit tissue penetration, and can have very specific high-affinity antigen-binding abilities.
These therapeutic sdAbs may improve accessibility to those in need, with the ease of production and potential for no refrigeration needed. Antivenom made of single domain antibodies have now provided exceptional therapeutic candidates able to bind to a broad spectrum of toxins.
Quote:
"We worked with ProSci to develop an antibody phage display library from which candidates could be selected. We were impressed with the scientific expertise ProSci brought to our project as well as the attention to detail given at every juncture. Looking forward to future collaboration with them!"
-Dan Dempsey, CEO, Venomyx Therapeutics
