title: 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.affiliation: HKU-Pasteur Research Centre, 8 Sassoon Road, Hong Kong SAR, China. Jasonkamyiuwing@yahoo.com.hk
authors.forename: Yiu Wing
authors.initials: YW
authors.lastname: Kam
authors.forename: François
authors.initials: F
authors.lastname: Kien
authors.forename: Anjeanette
authors.initials: A
authors.lastname: Roberts
authors.forename: Yan Chung
authors.initials: YC
authors.lastname: Cheung
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Lamirande
authors.forename: Leatrice
authors.initials: L
authors.lastname: Vogel
authors.forename: Shui Ling
authors.initials: SL
authors.lastname: Chu
authors.forename: Jane
authors.initials: J
authors.lastname: Tse
authors.forename: Jeannette
authors.initials: J
authors.lastname: Guarner
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: Malik
authors.initials: M
authors.lastname: Peiris
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nal
authors.forename: Ralf
authors.initials: R
authors.lastname: Altmeyer
mesh_terms: 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*
chemical_list: 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