Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcgammaRII-dependent entry into B cells in vitro

Vaccine. 2007 Jan 8;25(4):729-40. doi: 10.1016/j.vaccine.2006.08.011. Epub 2006 Aug 22.

Abstract

Vaccine-induced antibodies can prevent or, in the case of feline infectious peritonitis virus, aggravate infections by coronaviruses. We investigated whether a recombinant native full-length S-protein trimer (triSpike) of severe acute respiratory syndrome coronavirus (SARS-CoV) was able to elicit a neutralizing and protective immune response in animals and analyzed the capacity of anti-S antibodies to mediate antibody-dependent enhancement (ADE) of virus entry in vitro and enhancement of replication in vivo. SARS-CoV-specific serum and mucosal immunoglobulins were readily detected in immunized animals. Serum IgG blocked binding of the S-protein to the ACE2 receptor and neutralized SARS-CoV infection in vitro. Entry into human B cell lines occurred in a FcgammaRII-dependent and ACE2-independent fashion indicating that ADE of virus entry is a novel cell entry mechanism of SARS-CoV. Vaccinated animals showed no signs of enhanced lung pathology or hepatitis and viral load was undetectable or greatly reduced in lungs following challenge with SARS-CoV. Altogether our results indicate that a recombinant trimeric S protein was able to elicit an efficacious protective immune response in vivo and warrant concern in the safety evaluation of a human vaccine against SARS-CoV.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • B-Lymphocytes / metabolism*
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Immunity, Mucosal
  • Immunoglobulin A / metabolism
  • Immunoglobulin G / metabolism
  • Membrane Glycoproteins / immunology*
  • Mice
  • Receptors, IgG / metabolism*
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / immunology*

Substances

  • Antibodies, Viral
  • Immunoglobulin A
  • Immunoglobulin G
  • MHV surface projection glycoprotein
  • Membrane Glycoproteins
  • Receptors, IgG
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV