Nanosized Neutralizing Antibodies for Diagnosing and Treating COVID-19
Screening, optimizing, and producing stable, specific, recombinant nanobodies against SARS-CoV-2
Nanobodies have strong potential for rapid, low-cost, reliable COVID-19 diagnostics and therapeutics. Nanobodies are high-affinity, stable antibodies of about 100 amino acids that are easily produced by bacteria as recombinant proteins. This feature allows them to be engineered and optimized for properties such virus neutralization. Nanobodies are one-tenth the size of monoclonal antibodies, so they are more stable and resistant to denaturation. This makes them suitable for use in point-of-care diagnostic tests and nebulized therapy for direct delivery to the lungs using an inhaler. Nanobodies originate from the unique single-chain antibodies of domesticated llamas.
The first nanobodies described for potential use in COVID-19 diagnostics and therapeutics recognized other coronaviruses and were screened for crossreactivity against the COVID-19 virus. Dr. Aitchison is developing libraries of nanobodies specific to the novel coronavirus because they are derived from llamas immunized with SARS-CoV-2 spike and nucleocapsid proteins. The first results indicate that the nanobodies from the Aitchison lab have binding affinities 1000-times higher than previously reported.
Often within 2 weeks of obtaining blood from immunized animals, the Aitchison group can identify nanobodies with picomolar affinity for SARS-CoV-2 proteins. Mass spectrometry determines the amino acid sequence of the best candidate nanobodies and RNA-seq data from the donor llama yields sequences for their expression in E. coli.
The Aitchison lab will soon be screening at least 100 nanobodies each against the SARS-CoV-2 spike and nucleocapsid proteins—more than 10 times more than previously available. They have the expertise and facilities to test binding affinity by surface plasmon resonance and virus neutralization assays.
Dr. Aitchison is interested in partnerships to develop his anti-SARS-CoV-2 nanobodies into clinical resources. Potential applications include rapid, point-of-care COVID-19 diagnosis from mucous or saliva samples using lateral-flow technology on simple teststrips. The exceptional stability of nanobodies makes them ideal for direct delivery via nebulizer of virus-neutralizing agents to prevent or treat active infections.
Stage of Development
- Preclinical in vitro
Collaborative development of COVID-19 diagnostics and therapeutics
Fridy PC, Li Y, Keegan S, Thompson MK, Nudelman I, Scheid JF, Oeffinger M, Nussenzweig MC, Fenyö D, Chait BT, Rout MP. A robust pipeline for rapid production of versatile nanobody repertoires. Nat Methods 2014. 11(12):1253-60.