title: Immunogenicity and protective efficacy in mice and hamsters of a β-propiolactone inactivated whole virus SARS-CoV vaccine.
abstract: The immunogenicity and efficacy of β-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01(B) and AS03(A) were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine. We evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of vaccine dose with or without the AS01(B) adjuvant on the immunogenicity and efficacy in hamsters. Efficacy was evaluated by challenge with wild-type virus at early and late time points (4 and 18 wk post-vaccination). A single dose of vaccine with or without adjuvant was poorly immunogenic in mice; a second dose resulted in a significant boost in antibody levels, even in the absence of adjuvant. The use of adjuvants resulted in higher antibody titers, with the AS01(B)-adjuvanted vaccine being slightly more immunogenic than the AS03(A)-adjuvanted vaccine. Two doses of WI-SARS with and without Adjuvant Systems were highly efficacious in mice. In hamsters, two doses of WI-SARS with and without AS01(B) were immunogenic, and two doses of 2 μg of WI-SARS with and without the adjuvant provided complete protection from early challenge. Although antibody titers had declined in all groups of vaccinated hamsters 18 wk after the second dose, the vaccinated hamsters were still partially protected from wild-type virus challenge. Vaccine with adjuvant provided better protection than non-adjuvanted WI-SARS vaccine at this later time point. Enhanced disease was not observed in the lungs or liver of hamsters following SARS-CoV challenge, regardless of the level of serum neutralizing antibodies.
authors.affiliation: Laboratory of Infectious Diseases, (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
authors.forename: Anjeanette
authors.initials: A
authors.lastname: Roberts
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Lamirande
authors.forename: Leatrice
authors.initials: L
authors.lastname: Vogel
authors.forename: Benoît
authors.initials: B
authors.lastname: Baras
authors.forename: Geneviève
authors.initials: G
authors.lastname: Goossens
authors.forename: Isabelle
authors.initials: I
authors.lastname: Knott
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Ward
authors.forename: Ventzislav
authors.initials: V
authors.lastname: Vassilev
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D006224:Cricetinae; D004202:Disinfectants / Q000494:pharmacology; D005260:Female; D007117:Immunization, Secondary / Q000379:methods; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D011420:Propiolactone / Q000494:pharmacology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000517:prevention & control*; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D038301:Virus Inactivation
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004202:Disinfectants; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D011420:Propiolactone