R&D 100 of the day: Potent and Effective Synthetic SARS-CoV-2 Neutralizing Nanobodies

The COVID-19 pandemic caused by SARS-CoV-2 resulted in 176 million cases, 3.81 million deaths, and an estimated global economic cost of over 10.3 trillion dollars. As variants of SARS-CoV-2 emerge, it is essential to possess a diverse set of preventative and therapeutic tools to maintain the progress made toward ending this pandemic. While vaccines are proving successful, antibody therapeutics are emerging as a critical tool in preventing those who are infected from becoming severely ill. Sandia researchers have identified and characterized several anti-SARS-CoV-2 neutralizing nanobodies (VHH) from a Sandia-designed proprietary next generation synthetic nanobody phage display library. Nanobody-based humanized (hu) heavy chain antibodies (nanobody-huFc) were produced, for the top 54 nanobodies identified, as a fusion to the hinge region and crystallizable fragment (Fc) domain of a human immunoglobulin G (IgG)1. This combines the advantages of nanobodies with the improved half-life and effector functions of human IgG while reducing the overall size by half that of a conventional antibody, making them easier to produce and better able to circulate to and penetrate target tissues in the body.