Broad neutralization of SARS-related viruses by human monoclonal antibodies

Science. 2020 Aug 7;369(6504):731-736. doi: 10.1126/science.abc7424. Epub 2020 Jun 15.

Abstract

Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Viral / immunology*
  • Antibody Affinity
  • B-Lymphocyte Subsets / immunology
  • Betacoronavirus / immunology*
  • Binding Sites
  • Broadly Neutralizing Antibodies / immunology*
  • Cross Reactions
  • Epitopes
  • Female
  • Humans
  • Immunologic Memory
  • Male
  • Middle Aged
  • Neutralization Tests
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism
  • Protein Domains
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / immunology
  • Somatic Hypermutation, Immunoglobulin
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • Epitopes
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • coronavirus receptors
  • spike glycoprotein, human coronavirus (HCV)
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Supplementary concepts

  • severe acute respiratory syndrome coronavirus 2