title: Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry.
abstract: The only severe acute respiratory syndrome (SARS) vaccine currently being tested in clinical trial consists of inactivated severe acute respiratory syndrome-associate coronavirus (SARS-CoV). However, limited information is available about host immune responses induced by the inactivated SARS vaccine. In this study, we demonstrated that SARS-CoV inactivated by beta-propiolactone elicited high titers of antibodies in the immunized mice and rabbits that recognize the spike (S) protein, especially the receptor-binding domain (RBD) in the S1 region. The antisera from the immunized animals efficiently bound to the RBD and blocked binding of RBD to angiotensin-converting enzyme 2, the functional receptor on the susceptible cells for SARS-CoV. With a sensitive and quantitative single-cycle infection assay using pseudovirus bearing the SARS-CoV S protein, we demonstrated that mouse and rabbit antisera significantly inhibited S protein-mediated virus entry with mean 50% inhibitory titers of 1:7393 and 1:2060, respectively. These data suggest that the RBD of S protein is a major neutralization determinant in the inactivated SARS vaccine which can induce potent neutralizing antibodies to block SARS-CoV entry. However, caution should be taken in using the inactivated SARS-CoV as a vaccine since it may also cause harmful immune and/or inflammatory responses.
authors.affiliation: Viral Immunology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021, USA.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: He
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Pamela
authors.initials: P
authors.lastname: Siddiqui
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology; D002268:Carboxypeptidases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D007703:Peptidyl-Dipeptidase A; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D007106:Immune Sera; D011991:Receptors, Virus; D011994:Recombinant Proteins; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2