Human Monoclonal Antibodies against SARS-CoV-2

SARS-CoV-2, the virus at the root of the deadly 2020 pandemic, shares several structural features with the closely related SARS-CoV virus that emerged in 2002 but was quickly contained. Both viruses cause acute respirator distress syndrome and share a high degree of homology, except for the receptor binding domain (RBD) on the spike (S) protein, which binds to the human ACE2 receptor that mediates viral cell entry. Neutralizing antibodies developed against SARS-CoV that targeted the RBD are ineffective against SARS-CoV-2, leading to a vast need for human monoclonal antibodies (mAbs) that specifically target the RBD on SARS-CoV-2.

Description

Pitt researchers have developed neutralizing human mAbs that specifically target the SARS-CoV-2 RBD using large phage displayed antibody libraries for use in preventing and treating SARS-CoV-2. Two high-affinity binders neutralized the virus by competing with ACE2 for binding with the receptor. One other candidate did not compete significantly with ACE2, but could induce antibody-dependent cellular cytotoxicity (ADCC), killing infected cells. Presently, these are the first human mAbs that can bind to the RBD and neutralize the virus.

Applications

· Preventing COVID-19
· Treating COVID-19

Advantages

· No other human monoclonal antibodies to SARS-CoV-2 have been identified
· Candidates can prevent viral cell entry or induce killing of infected cells

Invention Readiness

In vitro data

IP Status

https://patents.google.com/patent/US10822379B1

Related Publication(s)

Chen, C., Sun, Z., Liu, X., Li, W., & Dimitrov, D. S. (2021). Protocol for constructing large size human antibody heavy chain variable domain (VH) library and selection of SARS-CoV-2 neutralizing antibody domains. STAR Protocols, 2(3), 100617. https://doi.org/10.1016/j.xpro.2021.100617

Sun, Z., Chen, C., Li, W., Martinez, D. R., Drelich, A., Baek, D.-S., Liu, X., Mellors, J. W., Tseng, C.-T., Baric, R. S., & Dimitrov, D. S. (2020). Potent neutralization of SARS-CoV-2 by human antibody heavy-chain variable domains isolated from a large library with a new stable scaffold. mAbs, 12(1). https://doi.org/10.1080/19420862.2020.1778435