Research Project: Identifying Nanobody Proteins to Neutralize COVID-19 Viruses
COVID-19 Respiratory Virus Research Award
basic biologic mechanisms
SARS-CoV-2, the virus that causes COVID-19, has killed millions and is estimated to have infected about 10% of the world’s population. Despite the promise of vaccines, there is no clear end to the pandemic and there are significant challenges with current vaccine and monoclonal antibody strategies. Proteins called nanobodies are a very attractive and powerful addition to the multi-pronged arsenal we require to overcome the virus. They are produced in bacteria, but derived from llama antibodies. We have generated a large repertoire of nanobodies that are extremely potent at viral neutralization and are positioned to be superior therapeutics to prevent SARS-CoV-2 infection. We will identify highly effective nanobody cocktails that prevent infection and respiratory disease in mouse models exposed to Delta or Omicron. Our goal is to develop inhaled delivery of nanobodies that complement vaccines and drugs. They could serve critically ill patients, act as preventive treatment, and retain effectiveness with new variants.
We have identified a large and diverse collection of nanobodies that are potent neutralizers of all current variants of SARS-CoV-2. In laboratory tests, we found that combinations of these nanobodies have synergistic activities in neutralizing the virus. These nanobody combinations have also shown promise in a mouse model, significantly reducing viral loads compared to either nanobody delivered alone. In the coming year, we will optimize these nanobodies and test them against additional virus variants as they emerge, positioning nanobodies for clinical trials. Our innovative research offers a promising new therapeutic strategy against COVID-19 and future pandemic threats with great potential for improving public health.