We collaborated with scientists from GlaxoSmithKline Biologicals to evaluate the immunogenicity and efficacy of β−propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01B and AS03A 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 AS01B 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 weeks 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 AS01B adjuvanted vaccine being slightly more immunogenic than the AS03A 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 AS01B were immunogenic and two doses of 2 μg 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 weeks 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. The goal of our SARS program was driven by the public health need in 2003 for animal models for the evaluation of vaccines and immunoprophylaxis strategies. We developed mouse, hamster and non-human primate models and collaborated with several scientists from academic institutions and pharmaceutical companies to evaluate the efficacy of candidate vaccines. We have also investigated the pathogenesis of disease in the murine models of SARS. However, since SARS has not reappeared in epidemic form and pandemic influenza is a more imminent threat, we have discontinued active research in SARS and have re-directed the resources to work on pandemic influenza vaccines.
