Centaur antibodies: Engineered chimeric equine-human recombinant antibodies

Area of Science:

• Immunology
• Biotechnology
• Pharmacology

Background:

• Equine antisera are vital for treating intoxications but face challenges like recipient reactivity and limited supply.
• Next-generation immunotherapies are needed to address public health concerns related to current treatments.

Purpose of the Study:

• To develop novel tools for equine antibody engineering.
• To generate and characterize novel therapeutic antibodies for treating botulism.

Main Methods:

• Designed a new primer set (EquPD v2020) for amplifying equine antibody V-segments.
• Constructed immune phage display libraries from horses immunized with botulinum neurotoxins A and B.
• Selected and engineered scFv clones into full-length "Centaur antibodies" with equine V-genes and human constant regions.

Main Results:

• Successfully amplified and engineered equine antibody V-segments using the novel primer set.
• Generated diverse phage display libraries representing equine antibody repertoires.
• Identified specific scFv clones and developed Centaur antibodies with demonstrated therapeutic potential in a murine botulism model.

Conclusions:

• The developed tools enable efficient isolation and engineering of therapeutic equine antibodies.
• "Centaur antibodies" show promise as an alternative immunotherapy for botulism.
• This approach advances the development of next-generation immunotherapeutics.