Wang, Lingshu (NIAID)
Mascola, John (ModeX Therapeutics LLC)
Douek, Daniel (NIAID)
Sullivan, Nancy (NIAID)
Koup, Richard (NIAID)
Chen, Man (NIAID)
Shi, Wei (NIAID)
Zhang, Yi (NIAID)
Yang, Eun (NIAID)
Doria-Rose, Nicole (NIAID)
Schramm, Chaim (NIAID)
Birungi-Huff, Kevina (National Institute of Allergy and Infectious Diseases (NIAID/NIH))
Bush, Sabrina (NIAID)
Musayev, Maryam (National Institute of Allergy and Infectious Diseases)
Emergence of highly transmissible SARS-CoV-2 variants of concern that are resistant to current therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies.
Scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases have engineered a group of human monoclonal antibodies that target epitopes on the receptor binding domain of SARS-CoV-2 spike protein. These engineered antibodies ultra-potently neutralize >12 variants of SARS-CoV-2, including the highly transmissible BA.4 and BA.5 subvariants of Omicron, as shown in a pseudovirus neutralization assay. These engineered antibodies target 3 distinct epitopes in the receptor binding domain of the spike protein and function by blocking ACE2 binding. These engineered antibodies are not impacted by spike mutations that knockout binding to other therapeutic antibodies, including E484K, N439K, Y453F, L452R and K417N. Several of the engineered antibodies are able to simultaneously bind to the spike protein and are compatible for use in combination therapies. In in vitro assays, these combinations were shown to decrease the appearance of escape mutants suggesting the potential to mitigate resistance development when used as combination therapy. Additionally, these engineered antibodies are better suited for manufacturing than the parental antibodies.
This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404.