A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses.
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.
Spruth
Martin
M
Baxter Vaccines, Biomedical Research Centre, Uferstr. 15, 2304 Orth/Donau, Austria. martin.spruth@baxter.com
Kistner
Otfried
O
Savidis-Dacho
Helga
H
Hitter
Elisabeth
E
Crowe
Brian
B
Gerencer
Marijan
M
Brühl
Peter
P
Grillberger
Leopold
L
Reiter
Manfred
M
Tauer
Christa
C
Mundt
Wolfgang
W
Barrett
P Noel
PN
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*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines