Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants.
Lingshu WangTongqing ZhouYi ZhangEun Sung YangChaim A SchrammWei ShiAmarendra PeguOlamide K OloniniyiAmy R HenrySamuel W DarkoSandeep R NarpalaChristian HatcherDavid R MartinezYaroslav TsybovskyEmily PhungOlubukola M AbionaAvan AntiaEvan M CaleLauren A ChangMisook ChoeKizzmekia S Corbett-HelaireRachel L DavisAnthony T DiPiazzaIngelise J GordonSabrina Helmold HaitTandile HermanusPrudence KgagudiFarida LabouneKwanyee LeungTracy LiuRosemarie D MasonAlexandra F NazzariLaura NovikSarah O'ConnellSijy O'DellAdam S OliaStephen D SchmidtTyler StephensChristopher D StringhamChloe Adrienna TalanaI-Ting TengDanielle A WagnerAlicia T WidgeBaoshan ZhangMario RoedererJulie E LedgerwoodTracy J RuckwardtMartin R GaudinskiPenny L MooreNicole A Doria-RoseRalph S BaricBarney S GrahamAdrian B McDermottDaniel C DouekPeter D KwongJohn R MascolaNancy J SullivanJohn MisasiPublished in: Science (New York, N.Y.) (2021)
The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC50) 0.3 to 11.1 nanograms per milliliter; IC80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.