Identification of Novel Neutralizing Monoclonal Antibodies against SARS-CoV-2 Spike Glycoprotein

Devivasha Bordoloi; Ziyang Xu; Michelle Ho; Mansi Purwar; Pratik Bhojnagarwala; Joel Cassel; Leila B Giron; Susanne Walker; Abhijeet J Kulkarni; Edgar Tello Ruiz; Jihae Choi; Faraz I Zaidi; Yuanhan Wu; Shaoying Wang; Ami Patel; Stephanie Ramos; Trevor Smith; Daniel Kulp; Kenneth E Ugen; Alagarsamy Srinivasan; Mohamed Abdel-Mohsen; Laurent Humeau; David B Weiner; Kar Muthumani

doi:10.1021/acsptsci.1c00058

Identification of Novel Neutralizing Monoclonal Antibodies against SARS-CoV-2 Spike Glycoprotein

ACS Pharmacol Transl Sci. 2021 Jul 29;4(4):1349-1361. doi: 10.1021/acsptsci.1c00058. eCollection 2021 Aug 13.

Authors

Devivasha Bordoloi¹, Ziyang Xu¹, Michelle Ho¹, Mansi Purwar¹, Pratik Bhojnagarwala¹, Joel Cassel², Leila B Giron¹, Susanne Walker¹, Abhijeet J Kulkarni¹, Edgar Tello Ruiz¹, Jihae Choi¹, Faraz I Zaidi¹, Yuanhan Wu¹, Shaoying Wang³, Ami Patel¹, Stephanie Ramos⁴, Trevor Smith⁴, Daniel Kulp¹, Kenneth E Ugen⁵, Alagarsamy Srinivasan⁶, Mohamed Abdel-Mohsen¹, Laurent Humeau⁴, David B Weiner¹, Kar Muthumani¹

Affiliations

¹ Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania 19104-4205, United States.
² Molecular Screening Facility, The Wistar Institute, Philadelphia, Pennsylvania 19104,United States.
³ Synbio Technologies, Monmouth Junction, New Jersey 08852, United States.
⁴ Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania 19462, United States.
⁵ Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida 33612, United States.
⁶ NanoBio Diagnostics, West Chester, Pennsylvania 19382, United States.

Abstract

Coronavirus disease 2019 (COVID-19) is caused by the newly emerged human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the highly contagious nature of SARS-CoV-2, it has infected more than 137 million individuals and caused more than 2.9 million deaths globally as of April 13, 2021. There is an urgent need to develop effective novel therapeutic strategies to treat or prevent this infection. Toward this goal, we focused on the development of monoclonal antibodies (mAbs) directed against the SARS-CoV-2 spike glycoprotein (SARS-CoV-2 Spike) present on the surface of virus particles as well as virus-infected cells. We isolated anti-SARS-CoV-2 Spike mAbs from animals immunized with a DNA vaccine. We then selected a highly potent set of mAbs against SARS-CoV-2 Spike protein and evaluated each candidate for their expression, target binding affinity, and neutralization potential using complementary ACE2-blocking and pseudovirus neutralization assays. We identified a total of 10 antibodies, which specifically and strongly bound to SARS-CoV-2 Spike, blocked the receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) interaction, and neutralized SARS-CoV-2. Furthermore, the glycomic profile of the antibodies suggested that they have high Fc-mediated effector functions. These antibodies should be further investigated for elucidating the neutralizing epitopes on Spike for the design of next-generation vaccines and for their potential in diagnostic as well as therapeutic utilities against SARS-CoV-2.