Abstract
SummaryNeutralizing 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 S1A 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.
Highlights
A newly emergent betacoronavirus, SARS-CoV-2, resulted in a pandemic in 2020, causing the respiratory disease COVID-19 (Wu et al, 2020b; Zhou et al, 2020)
Convalescent Plasma immunoglobulin Gs (IgGs) and Fab Binding Properties Demonstrate Recognition of Diverse Coronaviruses and Effects of Avidity Convalescent plasma samples were collected from individuals who had recovered from COVID-19 at Rockefeller University Hospital (Robbiani et al, 2020)
Among the plasmas (COV21, COV57, and COV107) chosen for further analysis based on ELISA EC50 values and neutralization potencies (Robbiani et al, 2020), IgGs from COV21 and COV57 showed the strongest binding to the S proteins from SARS-CoV-2 and SARS-CoV, with only the COV57 IgGs showing measurable binding to MERS-CoV S protein
Summary
A newly emergent betacoronavirus, SARS-CoV-2, resulted in a pandemic in 2020, causing the respiratory disease COVID-19 (Wu et al, 2020b; Zhou et al, 2020). SARS-CoV-2 is the third zoonotic betacoronavirus to infect humans this century, following SARS-CoV and MERS-CoV (Middle East respiratory syndrome) infections in 2003 and 2012, respectively (de Wit et al, 2016). Neutralizing antibody responses against SARS-CoV-2, SARSCoV, and MERS-CoV S proteins often target the receptor-binding domain (RBD; called the S1B domain) (Hwang et al, 2006; Pinto et al, 2020; Prabakaran et al, 2006; Reguera et al, 2012; Rockx et al, 2008; Walls et al, 2019, 2020; Widjaja et al, 2019; Wrapp and McLellan, 2019; Wrapp et al, 2020).
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