Targeting the Spike Receptor Binding Domain Class V Cryptic Epitope by an Antibody with Pan-Sarbecovirus Activity

Author:

Jensen Jaime L.12,Sankhala Rajeshwer S.123,Dussupt Vincent123,Bai Hongjun123,Hajduczki Agnes12,Lal Kerri G.12,Chang William C.123,Martinez Elizabeth J.12,Peterson Caroline E.123,Golub Emily S.12,Rees Phyllis A.12,Mendez-Rivera Letzibeth123,Zemil Michelle23,Kavusak Erin23,Mayer Sandra V.4ORCID,Wieczorek Lindsay23,Kannan Shruthi5,Doranz Benjamin J.5,Davidson Edgar5,Yang Eun Sung6,Zhang Yi6,Chen Man6,Choe Misook6,Wang Lingshu6,Gromowski Gregory D.4,Koup Richard A.6,Michael Nelson L.7,Polonis Victoria R.3ORCID,Rolland Morgane123ORCID,Modjarrad Kayvon1,Krebs Shelly J.123,Joyce M. Gordon123ORCID

Affiliation:

1. Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

2. Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA

3. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

4. Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

5. Integral Molecular, Philadelphia, Pennsylvania, USA

6. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

7. Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

Abstract

Characterization of MAbs against SARS-CoV-2, elicited through vaccination or natural infection, has provided vital immunotherapeutic options for curbing the COVID-19 pandemic and has supplied critical insights into SARS-CoV-2 escape, transmissibility, and mechanisms of viral inactivation. Neutralizing MAbs that target the RBD but do not block ACE2 binding are of particular interest because the epitopes are well conserved within sarbecoviruses and MAbs targeting this area demonstrate cross-reactivity.

Funder

DOD | Defense Health Agency

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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