Severe acute respiratory syndrome (SARS), now known to be caused by the SARS coronavirus (SARS-CoV), emerged in China in 2002 and was responsible for more then 8,000 cases of respiratory disease and 774 deaths world-wide. The virus has re-emerged in China in 2004. The high mortality rate of SARS (over 50% in subjects aged over 60 and more than 10% in younger people) and the fact that most of the world's population is immunologically na?ve to the SARS coronavirus highlights the potential devastating impact that a SARS pandemic could have on human morbidity and mortality. Apart from strict patient isolation, there are currently no effective treatments for preventing the spread of SARS. However since SARS is caused by a respiratory virus, vaccination offers a potential way to control the disease. Vaccination by the mucosal route resulting in the production of protective slgA in the respiratory tract and IgG in serum is a particularly attractive goal.
The aim of this project is to develop a nasally administered subunit vaccine to protect against human SARS. Protollin is a potent mucosal adjuvant that induces protective mucosal and systemic antibody responses when given nasally. Protollin is safe and well tolerated in humans and has been shown to adjuvant a variety of antigens from various pathogens. In this study Protollin-adjuvant SARS-CoV Spike proteins expressed as baculovirus proteins will be initially tested for immunogenicity in mice. Formulations inducing optimal levels of SARS virus neutralizing activity in the serum of immunized animals will be further examined in ferret challenge models to evaluate their capacity to protect against infection with SARS virus. A candidate Protollin SARS S-protein vaccine will then be tested for safety in GLP toxicity studies. Once safety has been shown, the vaccine will be manufactured under GMP and evaluated for safety and immunogenicity in a human Phase I clinical trial. The goal is to rapidly initiate the clinical development to support licensure of a Protollin-based nasal subunit vaccine for SARS.
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