Shark Antibodies and Shark-Derived Binding Domains Specific for the SARS-CoV-2 Coronavirus - (HJF 581-20)

HJF scientists have developed a series of single variable domain antibodies (nanobodies or VNARs, derived from nurse sharks) specifically targeting SARS-CoV-2 and other betacoronaviruses, thus providing unique therapeutics and diagnostics for COVID-19 and possibly other betacoronavirus infections.

Applications and Advantages

Fully sequenced, grafted onto human Fc, and cloned in mammalian cells.
Bi- and tri-specificities to various epitopes.
Cross-activities against SARS-CoV-2 variants and divergent sarbecoviruses.
High affinity with sub-picomolar K_D
Proven to be efficacious in in vivo animal studies.
Suitable for use as therapeutics and diagnostic agents.

Innovation Description

Scientists from HJF, Walter Reed Army Institute of Research (WRAIR), and the University of Maryland Baltimore have developed a series of single variable domain antibodies (nanobodies or VNARs) derived from nurse sharks. These nanobodies and antigen-binding fragments thereof specifically bind to the SARS-CoV-2 Spike glycoprotein as well as the Spike glycoproteins of other coronaviruses. These specific nanobodies and antigen-binding fragments thereof can be used for diagnosing SARS-CoV-2 infection and associated diseases, including COVID-19, as well as for preventing and/or treating SARS-CoV-2 coronavirus infection. These nanobodies and antigen-binding fragments thereof can also be utilized for immunogen testing and validation, viral inhibition, and other applications related to SARS-CoV-2. These nanobodies and antigen-binding fragments thereof may be used for the development of antibody therapeutics and/or use in vaccine immunogen development and product release. Sequences encoding the antigen specific antigen-binding domain are derived from a variable region of the immunoglobulin isotype IgNAR found in cartilaginous fishes. The nanobodies and antigen-binding fragments thereof can be linked together and/or conjugated to other proteins to form derivative binding molecules, including binding molecules with multi-specific reactivity against different epitopes of the SARS-Co V-2 Spike glycoprotein.

Figure 1. Shark nanobodies protective immunity in K18-ACE2 transgenic mice. NTD-targeting antibody ShAb06a alone or in combination with ShAb02a was given to K18-hACE2 mice one day prior to challenge. (A) Survival curves of K18-ACE2 mice (n=8/group, 4 female, 4 male). ( B) SARS-CoV-2 viral loads in BAL 2 days post-challenge in a subset of animals (n=5/group) by plaque assay. (C) Body weight changes were measured daily for each study mice. Percentage of initial weight is plotted. (D) Clinical score of the K18-hACE2 study groups.

Inventors

M. Gordon Joyce, Ph.D. HJF/WRAIR
Wei-Hung Chen, Ph.D. HJF/WRAIR
Agnes Hajduczki, Ph.D. HJF/WRAIR
Kayvon Modjarrad, M.D., Ph.D. WRAIR
Helen Dooley, Ph.D. University of Maryland, Baltimore

Innovation Status

A series of nanobodies have been sequenced, grafted onto human Fc, and cloned in mammalian cells, thus being ready for gram-quantity production. Extensive in vitro characterization and in vivo efficacy data are available.