Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1^A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

Benign colonization of the gut: Microbial communities in the gut can be highly individual. What engenders this specificity? The gut characteristically produces gram quantities of immunoglobulin A (IgA) antibody, which is presumed to protect the gut from pathogen attack. Donaldson et al. engineered strains of Bacteroides fragilis , a common human commensal, to modify its surface capsule, which affects its ability to colonize the germ-free mouse gut. Capsule changes altered the capacity of IgA to bind to the different mutants. It seems that this commensal species exploits IgA sticking power specifically to give it a competitive edge and to promote its establishment in the gut. Science , this issue p. 795