Bovine antibodies are unusual in having exceptionally long heavy chain CDR3 regions, with an average length of 25 amino acids, and an ‘ultralong’ subset that can reach >70 amino acids in length.
This latter subset of CDR3s independently fold into mini domains like bioactive venoms that often bind ion channels and GPCRs. Additionally, cows are unique in their capability to induce broadly neutralizing antibodies to HIV, with their ultralong CDR3s able to penetrate the glycan shield of the viral spike protein to bind cryptic epitopes.
The genetics and structural biology of this unusual antibody system has been studied in some detail, with advanced methods to identify therapeutically relevant bovine-based antibodies with long CDR3s developed. We will present an overview of cow antibody biology and their potential for novel therapeutic discovery.