title: A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses.
abstract: A double-inactivated, candidate whole virus vaccine against severe acute respiratory syndrome associated coronavirus (SARS-CoV) was developed and manufactured at large scale using fermenter cultures of serum protein free Vero cells. A two step inactivation procedure involving sequential formaldehyde and U.V. inactivation was utilised in order to ensure an extremely high safety margin with respect to residual infectivity. The immunogenicity of this double-inactivated vaccine was characterised in the mouse model. Mice that were immunised twice with the candidate SARS-CoV vaccine developed high antibody titres against the SARS-CoV spike protein and high levels of neutralising antibodies. The use of the adjuvant Al(OH)3 had only a minor effect on the immunogenicity of the vaccine. In addition, cell mediated immunity as measured by interferon-gamma and interleukin-4 stimulation, was elicited by vaccination. Moreover, the vaccine confers protective immunity as demonstrated by prevention of SARS-CoV replication in the respiratory tract of mice after intranasal challenge with SARS-CoV. Protection of mice was correlated to antibody titre against the SARS-CoV S protein and neutralising antibody titre.
authors.affiliation: Baxter Vaccines, Biomedical Research Centre, Uferstr. 15, 2304 Orth/Donau, Austria. martin.spruth@baxter.com
authors.forename: Martin
authors.initials: M
authors.lastname: Spruth
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
authors.forename: Helga
authors.initials: H
authors.lastname: Savidis-Dacho
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hitter
authors.forename: Brian
authors.initials: B
authors.lastname: Crowe
authors.forename: Marijan
authors.initials: M
authors.lastname: Gerencer
authors.forename: Peter
authors.initials: P
authors.lastname: Brühl
authors.forename: Leopold
authors.initials: L
authors.lastname: Grillberger
authors.forename: Manfred
authors.initials: M
authors.lastname: Reiter
authors.forename: Christa
authors.initials: C
authors.lastname: Tauer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mundt
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis*; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D004306:Dose-Response Relationship, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005285:Fermentation; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000517:prevention & control*; D046509:Tissue Culture Techniques; D015164:Vaccines, Inactivated / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines