Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Elisabetta Cameroni; Christian Saliba; John E. Bowen; Laura E. Rosen; Katja Culap; Dora Pinto; Laura A. VanBlargan; Anna De Marco; Samantha K. Zepeda; Julia di Iulio; Fabrizia Zatta; Hanna Kaiser; Julia Noack; Nisar Farhat; Nadine Czudnochowski; Colin Havenar-Daughton; Kaitlin R. Sprouse; Josh R. Dillen; Abigail E. Powell; Alex Chen; Cyrus Maher; Li Yin; David Sun; Leah Soriaga; Jessica Bassi; Chiara Silacci-Fregni; Claes Gustafsson; Helen Chu; Nicholas M. Franko; Jenni Logue; Najeeha Talat Iqbal; Ignacio Mazzitelli; Jorge Geffner; Renata Grifantini; Andrea Gori; Agostino Riva; Olivier Giannini; Alessandro Ceschi; Paolo Ferrari; Alessandra Franzetti-Pellanda; Christian Garzoni; Peter Halfmann; Yoshihiro Kawaoka; Christy Hebner; Lisa Purcell; Luca Piccoli; Matteo Samuele Pizzuto; Alexandra C Walls; Michael Diamond; Amalio Telenti; Herbert W Virgin; Antonio Lanzavecchia; David Veesler; Gyorgy Snell; Davide Corti.
Preprint
en Inglés
| PREPRINT-BIORXIV | ID: ppbiorxiv-472269
The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals. Most (26 out of 29) receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only three mAbs, including the ACE2-mimicking S2K146 mAb1, retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974, neutralized Omicron. The magnitude of Omicron-mediated immune evasion and the acquisition of binding to mouse ACE2 mark a major SARS-CoV-2 mutational shift. Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
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