Bovine Antibodies

Within the past few years, a lot of attention has been drawn to the unique structure of bovine antibodies. Around 10% of bovine antibodies have an ultra-long CDR3 loop which extends out of the Fab domain in the form of a “stalk.” This long CDR3 antibody stalk then leads into a “knob” which displays the majority of the antibody’s binding activity. This long CDR3 stalk is stabilized by both antiparallel B-sheets leading to and from the knob region and by forces from the residues in the other CDR loops. The knob region often contains between 4 and 12 cysteine residues that facilitate disulfide bonding which help maintain its stability. Together, these characteristics of bovine antibodies give rise to an extended binding domain that is capable of reaching into clefts, canyons and pores in proteins that are unreachable by typical IgG antibodies. 

ProSci BovineAntibody Binding Capacities

The knob shaped binding domain of the bovine long CDR3 antibody is quite different from the binding domain of the standard IgG antibody. The knob is heavily interwoven on itself due to the disulfide bonding which keeps it stable and forms a globular structure that displays the majority of binding activity. This globular binding domain makes bovine antibodies more ideal for concave binding sites. The stalk of the CDR3 loop adds to the knob’s binding ability by giving it extra range to reach into deeper binding sites in proteins, giving it access to deeper pores.

The Knob Binding Domain Advantage

The greatest advantage to the knob binding domain of bovine antibodies is the amount of binding diversity that comes with it. Binding capabilities of the knob of bovine antibodies are determined not just by the sequence, but by the pattern of which it is folded and the disulfide bonds that are formed. For instance, if there are 6 cysteine residues, the pattern of which disulfide bonds form (1-2, 1-5 etc) can dictate the types of epitopes the antibody will bind. This ability to have different binding capacities in the same amino acid sequence vastly increases binding diversity of these specialized bovine antibodies.

Projected Use & Applications

Bovine antibodies have been projected to be used in therapeutic applications because of their unique binding capacities. The elongated stalk and knob domain’s ability to reach into otherwise inaccessible regions will allow for the discovery of new functional antibodies with unseen effects. Inaccessible regions of interest may range from the inside of membrane channels to crevices in viral envelope proteins, potentially eliciting blocking or activating effects in different pathways.

ProSci's Bovine Antibody Development

Bovine antibody development is still a very new concept in comparison to mouse and rabbit antibody development. At this time, ProSci does have experience collecting serum and whole blood from bovine for different types of projects. Our privately owned NIH assured and USDA licensed animal facility in San Diego, California is capable of housing cattle and other large animals. If you are interesting in developing a bovine antibody against a difficult target, contact us at, or fill out the following form.


Smider, Vaughn. "NGAPA 2015 - Vaughn Smider, Scripps Research Institute, US." Vimeo. N.p., n.d. Web. 05 Aug. 2016.


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