Human monoclonal antibodies against SARS-CoV-2

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

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Principal Investigator: Joshua Hoong Yu  Tan
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2021
Award: $143,050
Funding agency: National Institute of Allergy and Infectious Diseases

The overarching goal of this project is to study the immune response to COVID-19 at the monoclonal level to increase our understanding of basic biology and develop new tools to combat disease. We have screened plasma from >100 acutely infected and convalescent COVID-19 individuals for neutralization of authentic SARS-CoV-2. The top neutralizers were selected for antibody isolation and we have isolated a panel of monoclonals against the SARS-CoV-2 spike protein. 

In FY21, we characterized a panel of >200 recombinant monoclonal antibodies against the SARS-CoV-2 spike protein. These antibodies bound to diverse sites on the spike protein, including the N-terminal domain (NTD), receptor-binding domain (RBD) and other sites. We tested the antibodies for neutralization of authentic SARS-CoV-2 and identified a panel of 8 potent antibodies. Interestingly, the top 3 potent RBD-specific antibodies targeted different regions of the domain, and all 3 neutralized the Alpha and Beta variants. We designed bispecific antibodies by combining antibodies with non-overlapping specificities and identified 5 bispecific antibodies that neutralized authentic SARS-CoV-2 at concentrations of <1 ng/mL. Several bispecific antibodies were comparably effective against the Alpha and Beta variants and wild-type SARS-CoV-2, and one bispecific antibody was shown to reduce weight loss and clinical symptoms in a hamster model of SARS-CoV-2 infection.

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