Human monoclonal antibodies against SARS-CoV-2

NIH Pandemic-Era Grants

Pandemic Era Grants

2023

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Principal Investigator: Joshua Hoong Yu  Tan
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2023
Award: $568,478
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 FY23, we focused on identifying broadly reactive monoclonal antibodies (mAbs) against coronaviruses. We isolated a panel of 61 antibodies that could bind diverse betacoronaviruses or alphacoronaviruses. We identified two groups of neutralizing mAbs; one group targeted the highly conserved fusion peptide and the other targeted the stem helix. The anti-fusion peptide mAbs broadly neutralized both alphacoronaviruses and betacoronaviruses, including all SARS-CoV-2 variants of concern (published in Science). The anti-stem helix mAbs neutralized only betacoronaviruses (including all SARS-CoV-2 variants of concern), but with higher potency than the anti-fusion peptide mAbs (published in Cell Host & Microbe, made the cover). Both types of mAb limited disease in a hamster model of SARS-CoV-2 infection and inhibited coronavirus fusion with target cells.

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