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

描述（由申请人提供）：严重急性呼吸系统综合征（SARS）是由一种新出现的冠状病毒引起的。在2002/2003年爆发期间，该病在国际上蔓延，导致总死亡率约为10%，老年人死亡率高达约40%。与其他冠状病毒一样，刺突(S)蛋白是中和抗体的主要目标。SARS-CoV S蛋白通过受体结合域（RBD）与受体血管紧张素转换酶2 （ACE2）结合。RBD具有免疫原性，是一种主要的中和性决定因子。针对疫苗开发进行了大量研究，但目前还没有可用的疫苗。人们仍然担心未来可能爆发SARS。该病毒的宿主尚未确定。sars冠状病毒是生物防御C类优先病原体。还有可能发生实验室获得性感染。因此，研制有效的疫苗仍然十分重要。该项目的长期目标是确定呈递SARS-CoV S蛋白RBD的植物源性病毒样颗粒是否能有效刺激针对SARS-CoV的保护性全身和粘膜免疫。在植物中，将RBD与乙型肝炎表面抗原（HBsAg）和核心抗原（HBcAg）融合表达，将产生显示RBD的新型异源VLPs。将评估含rbd的VLPs在小鼠中引发强烈的全身和粘膜sars - cov中和抗体反应和保护性免疫的能力。将使用标准分子生物学、生化方法、疫苗接种和免疫学分析。该项目的具体目标是：1。在植物中制备呈递SARS-CoV S RBD的异源VLPs和2。在小鼠模型上评价植物源性VLPs的免疫原性和保护作用。

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.