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Anti-SARS-CoV Spike Antibodies Trigger Infection of Human Immune Cell via a pH- and Cysteine Protease-Independent Fc{gamma}R Pathway.

Abstract : Public health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV). However, the precursor of the SARS-CoV remains in its natural bat reservoir and re-emergence of a human-adapted SARS-like coronavirus remains a plausible public health concern. Vaccination is a major strategy for containing resurgence of SARS in humans and a number of vaccine candidates have been tested in experimental animal models. We previously reported that antibody elicited by a SARS-CoV vaccine candidate based on recombinant full-length Spike-protein trimers potentiated infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents. These observations prompted us to investigate the mechanisms underlying antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro. Here we demonstrate that anti-Spike immune serum, while inhibiting viral entry in a permissive cell line, potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles as well as replication-competent SARS coronavirus. Antibody-mediated infection was dependent on Fcγ receptor II but did not use the endosomal/lysosomal pathway utilized by angiotensin I converting enzyme 2 (ACE2), the accepted receptor for SARS-CoV. This suggests that ADE of SARS-CoV utilizes a novel cell entry mechanism into immune cells. Different SARS vaccine candidates elicit sera that differ in their capacity to induce ADE in immune cells, in spite of comparable potency to neutralize infection in ACE2-bearing cells. Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate potential pitfalls associated with immunization against it. They should prompt further investigations into SARS pathogenesis.
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Contributor : Francois Kien Connect in order to contact the contributor
Submitted on : Friday, July 29, 2011 - 6:21:40 AM
Last modification on : Thursday, April 7, 2022 - 10:10:16 AM

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Martial Jaume, Ming S Yip, Chung y Cheung, Hiu L Leung, Ping H Li, et al.. Anti-SARS-CoV Spike Antibodies Trigger Infection of Human Immune Cell via a pH- and Cysteine Protease-Independent Fc{gamma}R Pathway.. Journal of Virology, 2011, epub ahead of print. ⟨10.1128/JVI.00671-11⟩. ⟨pasteur-00612415⟩



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