Abstract
SARS-CoV-2 is a newly emerged betacoronavirus and the causative agent for the COVID-19 pandemic. Antibodies recognizing the viral spike protein are instrumental in natural and vaccine-induced immune responses to the pathogen and in clinical diagnostic and therapeutic applications. Unlike conventional immunoglobulins, the variable lymphocyte receptor antibodies of jawless vertebrates are structurally distinct, indicating that they may recognize different epitopes. Here we report the isolation of monoclonal variable lymphocyte receptor antibodies from immunized sea lamprey larvae that recognize the spike protein of SARS-CoV-2 but not of other coronaviruses. We further demonstrate that these monoclonal variable lymphocyte receptor antibodies can efficiently neutralize the virus and form the basis of a rapid, single step SARS-CoV-2 detection system. This study provides evidence for monoclonal variable lymphocyte receptor antibodies as unique biomedical research and potential clinical diagnostic reagents targeting SARS-CoV-2.
Highlights
Coronavirus disease 19 (COVID-19) emerged from Wuhan, China, in December 2019 and progressed into a global pandemic in 2020, with over 160 million cases and over 3 million deaths documented worldwide by the World Health Organization [1]
The LRRv units - typically the regions of greatest sequence diversity - of the VLRB B7 and VLRB B39 antibodies are identical whereas the remaining leucine-rich repeat (LRR) units and especially the C-terminal loop show numerous non-conserved residues
The similar antigen binding and virus neutralization characteristics of VLRB B7 and VLRB B39 raise the possibility that antigen recognition is primarily mediated by residues located within the three identical LRRv units
Summary
Coronavirus disease 19 (COVID-19) emerged from Wuhan, China, in December 2019 and progressed into a global pandemic in 2020, with over 160 million cases and over 3 million deaths documented worldwide by the World Health Organization [1]. Epitopes located on the viral S-protein RBD are targeted by most neutralizing antibodies isolated from COVID-19 convalescent or active patients [4,5,6,7]. The viral S-protein features prominently in multiple vaccination strategies and in antibody-based therapeutic approaches [8]. While conventional antibodies recognize a wide variety of antigens with high degree of specificity, they are typically only poorly reactive with certain antigens such as carbohydrate posttranslational protein modifications, a feature that contributes to glycan shielding as immune evasion mechanism of viral pathogens, including those of the family coronaviridae [9,10,11]. Exploring non-conventional antibody platforms for SARS-CoV-2 S-protein reactive antibodies is a promising strategy to isolate reagents aimed at exploiting vulnerabilities of the virus that conventional antibodies may not readily recognize
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