Development of a plant-derived virus-like particle vaccine against SARS-CoV

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DESCRIPTION (provided by applicant): Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus. During the outbreak in 2002/2003 the disease spread internationally resulting in an overall mortality rate of ~10% and a significantly higher rate of ~40% for elderly individuals. As is the case with other coronaviruses, the spike (S) protein is the major target for neutralizing antibodies. SARS-CoV S protein binds to the receptor, angiotensin-converting enzyme 2 (ACE2), through its receptor binding domain (RBD). The RBD is immunogenic and is a major neutralizing determinant. Significant research has been directed toward vaccine development, but none is yet available. Concerns remain over the possibility of future outbreaks of SARS. The reservoir for the virus has not been identified. SARS-CoV is a Biodefense Category C priority pathogen. There is also the potential for laboratory acquired infections. Thus, development of effective vaccines is still of significant importance. The long-term goal of this project is to determine if plant-derived virus-like particles presenting the RBD of the SARS-CoV S protein can efficiently stimulate protective systemic and mucosal immunity against SARS-CoV. Novel heterologous VLPs displaying the RBD will be generated by expressing the RBD as fusions with the hepatitis B surface (HBsAg) and core (HBcAg) antigens in plants. RBD-containing VLPs will be evaluated for their ability to elicit strong systemic and mucosal SARS-CoV-neutralizing antibody responses and protective immunity in mice. Standard molecular biology, biochemical approaches, vaccination and immunological assays will be used. The specific aims of the project are: 1. To produce heterologous VLPs presenting the SARS-CoV S RBD in plants; and 2. To evaluate the immunogenicity and protective efficacy of plant-derived VLPs in mouse models. PUBLIC HEALTH RELEVANCE: Severe acute respiratory syndrome (SARS) caused by a new coronavirus (SARS-CoV) is new disease that appeared in 2002/2003 which caused a significant number of infections and deaths worldwide, with a mortality rate of at least 40% in older individuals. Even though the global outbreak was contained, there are concerns that the virus will reemerge or that it could potentially be used as a bioterrorist agent, thus it is important to develop safe effective vaccines. The long term goal of this project is to develop a novel subunit vaccine that elicits protection against SARS coronavirus.