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

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.

• Authors: Yiu Wing Kam, François Kien, Anjeanette Roberts, Yan Chung Cheung, Elaine W Lamirande, Leatrice Vogel, Shui Ling Chu, Jane Tse, Jeannette Guarner, Sherif R Zaki, Kanta Subbarao, Malik Peiris, Béatrice Nal, Ralf Altmeyer
• Journal: Vaccine (Vaccine) Vol. 25 Issue 4 Pg. 729-40 (Jan 08 2007) ISSN: 0264-410X [Print] Netherlands
• PMID: 17049691 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Immunoglobulin A
• Immunoglobulin G
• Membrane Glycoproteins
• Receptors, IgG
• Spike Glycoprotein, Coronavirus
• Viral Envelope Proteins
• spike glycoprotein, SARS-CoV
• spike protein, mouse hepatitis virus

Topics

• 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)
• Severe acute respiratory syndrome-related coronavirus (immunology)
• Severe Acute Respiratory Syndrome (prevention & control)
• Spike Glycoprotein, Coronavirus
• Viral Envelope Proteins (immunology)