Antibody-based therapeutics against Nipah virus

The spillover of emerging RNA viruses from their natural reservoirs into human populations continuously threatens global health. Antiviral monoclonal antibodies are an attractive approach to combating infection by emerging viruses, and FDA-approved drugs are now available to treat SARS-CoV-2 and Ebola virus infection. Nipah virus causes respiratory illness and encephalitis in humans with high fatality rates (50–100%) and can also be transmitted from person to person. However, there are no vaccines or drugs against Nipah virus infection, highlighting a critical gap in pandemic preparedness. Our laboratory has extensive experience isolating monoclonal antibodies from the peripheral blood mononuclear cells (PBMCs) of human convalescent donors. We will use antigen-specific B-cell sorting to isolate monoclonal antibodies from the PBMCs of survivors of Nipah virus infection. We will test antibodies for in vitro activity against Nipah virus and a related virus (Hendra virus). We will use structural studies to determine the basis for the antiviral activity of the most potent neutralizing antibodies and use in vitro assays to map potential resistance pathways. Our work will thus identify antiviral monoclonal antibodies that can be combined as cocktails to resist antibody neutralization escape and help meet an urgent need for medical countermeasures against Nipah virus.