SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement.
1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an FcγR-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation).
HKU-Pasteur Research Centre, 8 Sassoon Road, Hong Kong SAR, China. breizh@hku.hk
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Jaume
M S
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Yip
Y W
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Kam
C Y
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Cheung
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Kien
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A
Roberts
P H
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Li
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Dutry
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Escriou
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Daeron
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Bruzzone
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Subbarao
J S M
JS
Peiris
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Nal
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Altmeyer
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism*; D000914:Antibodies, Viral / Q000378:metabolism; D019067:Antibody-Dependent Enhancement; D045744:Cell Line, Tumor; D057056:Cysteine Proteases / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology* / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology*; D064370:Spike Glycoprotein, Coronavirus; D014612:Vaccines; D014759:Viral Envelope Proteins / Q000276:immunology*; D053586:Virus Internalization
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D064370:Spike Glycoprotein, Coronavirus; D014612:Vaccines; D014759:Viral Envelope Proteins; D057056:Cysteine Proteases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2