The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2

Authors: Ruiqi Huang, Gabrielle Warner Jenkins, Yunjeong Kim, Robyn L. Stanfield, Amrinder Singh, Maria Martinez-Yamout, Gerard J. Kroon, Jonathan L. Torres, Abigail M. Jackson, Abigail Kelley, Namir Shaabani, Baisen Zeng, Michael Bacica, Wen Chen, Christopher Warner, Jasmina Radoicic, Joongho Joh, Krishani Dinali Perera, Huldah Sang, Tae Kim, Jianxiu Yao, Fangzhu Zhao, Devin Sok, Dennis R. Burton, Jeff Allen, William Harriman, Waithaka Mwangi, Donghoon Chung, John R. Teijaro, Andrew B. Ward, H. Jane Dyson, Peter E. Wright, Ian A. Wilson, Kyeong-Ok Chang, Duncan McGregor, Vaughn V. Smider

Published: 2023-09-18

DOI: 10.1073/pnas.2303455120

Source: Full article


Abstract

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