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-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.
Kam
Yiu Wing
YW
HKU-Pasteur Research Centre, 8 Sassoon Road, Hong Kong SAR, China. Jasonkamyiuwing@yahoo.com.hk
Kien
François
F
Roberts
Anjeanette
A
Cheung
Yan Chung
YC
Lamirande
Elaine W
EW
Vogel
Leatrice
L
Chu
Shui Ling
SL
Tse
Jane
J
Guarner
Jeannette
J
Zaki
Sherif R
SR
Subbarao
Kanta
K
Peiris
Malik
M
Nal
Béatrice
B
Altmeyer
Ralf
R
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D017452:Receptors, IgG / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus