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Single domain shark VNAR antibodies neutralize SARS‐CoV‐2 infection in vitro
Author(s) -
Gauhar Aziz,
Privezentzev Cyril V.,
Demydchuk Mykhaylo,
Gerlza Tanja,
Rieger Julia,
Kungl Andreas J.,
Walsh Frank S.,
Rutkowski J. Lynn,
Stocki Pawel
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100986rr
Subject(s) - antibody , monoclonal antibody , epitope , virology , phage display , biology , in vitro , recombinant dna , neutralizing antibody , microbiology and biotechnology , epitope mapping , receptor , single domain antibody , antigen , coronavirus , virus , covid-19 , gene , immunology , biochemistry , medicine , disease , pathology , infectious disease (medical specialty)
Single domain shark variable domain of new antigen receptor (VNAR) antibodies can offer a viable alternative to conventional Ig‐based monoclonal antibodies in treating COVID‐19 disease during the current pandemic. Here we report the identification of neutralizing single domain VNAR antibodies selected against the severe acute respiratory syndrome coronavirus 2 spike protein derived from the Wuhan variant using phage display. We identified 56 unique binding clones that exhibited high affinity and specificity to the spike protein. Of those, 10 showed an ability to block both the spike protein receptor binding domain from the Wuhan variant and the N501Y mutant from interacting with recombinant angiotensin‐converting enzyme 2 (ACE2) receptor in vitro. In addition, three antibody clones retained in vitro blocking activity when the E484K spike protein mutant was used. The inhibitory property of the VNAR antibodies was further confirmed for all 10 antibody clones using ACE2 expressing cells with spike protein from the Wuhan variant. The viral neutralizing potential of the VNAR clones was also confirmed for the 10 antibodies tested using live Wuhan variant virus in in vitro cell infectivity assays. Single domain VNAR antibodies, due to their low complexity, small size, unique epitope recognition, and formatting flexibility, should be a useful adjunct to existing antibody approaches to treat COVID‐19.