The study investigates the escape of the SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Using a large cohort of convalescent and vaccinated individuals, the researchers found that mutations in the viral spike protein, particularly E484K, K417N, and N501Y, result in tighter binding to the ACE2 receptor and widespread escape from monoclonal antibody neutralization. The neutralization titers of convalescent and vaccinated sera against B.1.351 were significantly reduced, with some samples showing a complete inability to neutralize the virus. Structural analysis revealed that these mutations alter the binding interface of the RBD to ACE2, leading to reduced antibody binding and neutralization. The study highlights the need for further research to develop cocktails of antibodies to hedge against viral variants.The study investigates the escape of the SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Using a large cohort of convalescent and vaccinated individuals, the researchers found that mutations in the viral spike protein, particularly E484K, K417N, and N501Y, result in tighter binding to the ACE2 receptor and widespread escape from monoclonal antibody neutralization. The neutralization titers of convalescent and vaccinated sera against B.1.351 were significantly reduced, with some samples showing a complete inability to neutralize the virus. Structural analysis revealed that these mutations alter the binding interface of the RBD to ACE2, leading to reduced antibody binding and neutralization. The study highlights the need for further research to develop cocktails of antibodies to hedge against viral variants.