Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.
William N VossYixuan J HouNicole V JohnsonGeorge DelidakisJin Eyun KimKamyab JavanmardiAndrew P HortonFoteini BartzokaChelsea J ParesiYuri TannoChia-Wei ChouShawn A AbbasiWhitney PickensKatia GeorgeDaniel R BoutzDalton M TowersJonathan R McDanielDaniel BillickJule GoikeLori A RoweDhwani BatraJan PohlJustin LeeShivaprakash GangappaSuryaprakash SambharaMichelle V GadushNianshuang WangMaria D PersonBrent L IversonJimmy D GolliharJohn M DyeAndrew S HerbertIlya J FinkelsteinRalph S BaricJason S MclellanGeorge GeorgiouJason J LavinderGregory C IppolitoPublished in: Science (New York, N.Y.) (2021)
The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an amino (N)-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multidonor class of "public" antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that "public" NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape.