8edf

Publication Abstract from PubMed

Cows produce antibodies with a disulfide-bonded antigen-binding domain embedded within ultralong heavy chain third complementarity determining regions. This "knob" domain is analogous to natural cysteine-rich peptides such as knottins in that it is small and stable but can accommodate diverse loops and disulfide bonding patterns. We immunized cattle with SARS-CoV-2 spike and found ultralong CDR H3 antibodies that could neutralize several viral variants at picomolar IC(50) potencies in vitro and could protect from disease in vivo. The independent CDR H3 peptide knobs were expressed and maintained the properties of the parent antibodies. The knob interaction with SARS-CoV-2 spike was revealed by electron microscopy, X-ray crystallography, NMR spectroscopy, and mass spectrometry and established ultralong CDR H3-derived knobs as the smallest known recombinant independent antigen-binding fragment. Unlike other vertebrate antibody fragments, these knobs are not reliant on the immunoglobulin domain and have potential as a new class of therapeutics.

The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2.,Huang R, Warner Jenkins G, Kim Y, Stanfield RL, Singh A, Martinez-Yamout M, Kroon GJ, Torres JL, Jackson AM, Kelley A, Shaabani N, Zeng B, Bacica M, Chen W, Warner C, Radoicic J, Joh J, Dinali Perera K, Sang H, Kim T, Yao J, Zhao F, Sok D, Burton DR, Allen J, Harriman W, Mwangi W, Chung D, Teijaro JR, Ward AB, Dyson HJ, Wright PE, Wilson IA, Chang KO, McGregor D, Smider VV Proc Natl Acad Sci U S A. 2023 Sep 26;120(39):e2303455120. doi: , 10.1073/pnas.2303455120. Epub 2023 Sep 18. PMID:37722054^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.