Identification of nurse shark VNAR single‐domain antibodies targeting the spike S2 subunit of SARS‐CoV‐2
0301 basic medicine
0303 health sciences
SARS-CoV-2
Humans
COVID-19
Bacteriophages
Single-Domain Antibodies
Antibodies, Viral
Pandemics
Antibodies, Neutralizing
Antibodies
DOI:
10.1096/fj.202202099rr
Publication Date:
2023-05-16T15:29:56Z
AUTHORS (8)
ABSTRACT
AbstractSARS‐CoV‐2 is the etiological agent of the COVID‐19 pandemic. Antibody‐based therapeutics targeting the spike protein, specifically the S1 subunit or the receptor binding domain (RBD) of SARS‐CoV‐2, have gained attention due to their clinical efficacy in treating patients diagnosed with COVID‐19. An alternative to conventional antibody therapeutics is the use of shark new antigen variable receptor domain (VNAR) antibodies. VNARs are small (<15 kDa) and can reach deep into the pockets or grooves of the target antigen. Here, we have isolated 53 VNARs that bind to the S2 subunit by phage panning from a naïve nurse shark VNAR phage display library constructed in our laboratory. Among those binders, S2A9 showed the best neutralization activity against the original pseudotyped SARS‐CoV‐2 virus. Several binders, including S2A9, showed cross‐reactivity against S2 subunits from other β coronaviruses. Furthermore, S2A9 showed neutralization activity against all variants of concern (VOCs) from alpha to omicron (including BA1, BA2, BA4, and BA5) in both pseudovirus and live virus neutralization assays. Our findings suggest that S2A9 could be a promising lead molecule for the development of broadly neutralizing antibodies against SARS‐CoV‐2 and emerging variants. The nurse shark VNAR phage library offers a novel platform that can be used to rapidly isolate single‐domain antibodies against emerging viral pathogens.
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