A mucosally targeted MERS CoV vaccine produced in plants

DESCRIPTION provided by applicant Middle East Respiratory Syndrome MERS coronavirus MERS CoV causes severe acute respiratory illness with a high fatality rate among reported cases MERS was first reported in but the virus has been circulating in camels which are thought to be an animal reservoir for at least years To date over MERS cases have been reported to the World Health Organization including over deaths While most cases have been in Saudi Arabia and contact with camels or camel products has been implicated in some cases human to human transmission has been documented as well and the virus is thought to have epidemic potential There are currently no approved vaccines or therapeutics for MERS The MERS CoV spike S protein mediates viral entry into host cells expressing the viral receptor dipeptidyl peptidase DPP Within the S subunit a Receptor Binding Domain RBD of about amino acids has been identified Immunization of mice with a recombinant fusion protein containing S fused to human IgG Fc S Fc induced high titers of neutralizing antibodies in immunized animals Unfortunately expression of S Fc or RBD Fc in mammalian cell culture is low which may be an impediment for further development of this promising candidate vaccine We will circumvent the production problem by producing MERS CoV RBD Fc and modifications thereof using a well established plant expression system Our scalable transient plant expression system allows rapid production of recombinant protein within a week with protein production costs less than that of mammalian cell systems We will produce variants of MERS CoV RBD Fc with enhanced binding to the mouse neonatal Fc receptor FcRn in order to test the hypothesis that improved antigen presentation via FcRn will result in an enhanced immune response We will evaluate the immunogenicity of mucosally administered MERS CoV RBD Fc in mice by analyzing both humoral and cell mediated immunity We will evaluate titers of RBD specific antibodies analyze T cell responses by intracellular cytokine staining followed by flow cytometry analysis and will measure the ability of sera from immunized mice to neutralize live MERS CoV in vitro PUBLIC HEALTH RELEVANCE Middle East respiratory syndrome coronavirus MERS CoV also termed hCoV EMC was first identified in humans in in the Middle East To date andgt people have contracted MERS in countries resulting in andgt deaths Epidemiology studies suggest human to human transmission of this deadly virus leading to concern about a MERS pandemic Using a plant expression system we will develop an effective MERS CoV vaccine designed to be delivered to mucosal surfaces