Targeting the Spike Receptor Binding Domain Class V Cryptic Epitope by an Antibody with Pan-Sarbecovirus Activity
Jaime L. Jensen, Rajeshwer S. Sankhala, Vincent Dussupt, Hongjun Bai, Agnes Hajduczki, Kerri G. Lal, William C. Chang, Elizabeth J. Martinez, Caroline E. Peterson, Emily S. Golub, Phyllis A. Rees, Letzibeth Mendez-Rivera, Michelle Zemil, Erin Kavusak, Sandra V. Mayer, Lindsay Wieczorek, Shruthi Kannan, Benjamin J. Doranz, Edgar Davidson, Eun Sung Yang, Yi Zhang, Man Chen, Misook Choe, Lingshu Wang, Gregory D. Gromowski, Richard A. Koup, Nelson L. Michael, Victoria R. Polonis, Morgane Rolland, Kayvon Modjarrad, Shelly J. Krebs, Michael Joyce
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. The class V RBD-targeted MAbs localize to an invariant site of vulnerability, provide a range of neutralization potency, and exhibit considerable breadth against divergent sarbecoviruses, with implications for vaccine and therapeutic development.