Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease.
Panpan ZhouGe SongWan-Ting HeNathan BeutlerLongping V TseDavid R MartinezAlexandra SchäferFabio AnzanelloPeter YongLinghang PengKatharina DuekerRami MusharrafiehSean CallaghanTazio CapozzolaMeng YuanHejun LiuOliver LimboMara ParrenElijah GarciaStephen A RawlingsDavey M SmithDavid NemazeeJoseph G JardineIan A WilsonYana SafonovaThomas F RogersRalph S BaricLisa E GralinskiDennis R BurtonRaiees AndrabiPublished in: bioRxiv : the preprint server for biology (2022)
Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against coronaviruses that cause severe disease, for anticipating novel pandemic-causing viruses, and to respond more effectively to SARS-CoV-2 variants. The emergence of the Omicron variant of SARS-CoV-2 has illustrated the limitations of solely targeting the receptor binding domain (RBD) of the envelope Spike (S)-protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors that target a conserved S2 region in the fusion machinery on betacoronavirus spikes. Select bnAbs show broad in vivo protection against all three pathogenic betacoronaviruses, SARS-CoV-1, SARS-CoV-2 and MERS-CoV, that have spilled over into humans in the past 20 years to cause severe disease. The bnAbs provide new opportunities for antibody-based interventions and key insights for developing pan-betacoronavirus vaccines.