Vaccine
Volume 25, Issue 4, 8 January 2007, Pages 729-740
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 Altmeyere.
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 FcγRII-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.
Keywords
SARS-CoV, Protection, ADE