A human neutralizing antibody against a conformational epitope shared by oligomeric SARS S1 protein

Antivir Ther. 2006;11(1):117-23.

Abstract

An antibody phage-display library was constructed from the B cells of convalescent severe acute respiratory syndrome (SARS) patients and screened using inactivated SARS coronavirus (CoV) virions as antigens. More than 80 positive clones were isolated from the library and one of them, scFv H12, was extensively characterized. scFv H12 bound to SARS-CoV with high affinity (equilibrium dissociation constant, Kd=73.5 nM), and neutralized SARS virions in vitro. The facts that scFv H12 bound to the SARS-S1 protein under non-reducing conditions and that it did not bind to monomeric S1 protein under reducing conditions strongly suggest that scFv H12 recognizes a conformational epitope shared by oligomeric S1 proteins. This study should aid in the manufacture of neutralizing antibody, provide a better understanding the immunological characteristics of SARS protein and facilitate the design of a SARS vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / immunology*
  • Chlorocebus aethiops
  • Dimerization
  • Epitopes / chemistry
  • Epitopes / immunology
  • Humans
  • Immunoglobulin Fragments / chemistry
  • Immunoglobulin Fragments / immunology*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology*
  • Molecular Sequence Data
  • Neutralization Tests
  • Peptide Library
  • Protein Conformation
  • Severe acute respiratory syndrome-related coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus
  • Vero Cells
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / immunology*

Substances

  • Antibodies, Viral
  • Epitopes
  • Immunoglobulin Fragments
  • Membrane Glycoproteins
  • Peptide Library
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV