Developing a recombinanat vaccine for SARS

描述(申请人提供)：目前流行的严重急性呼吸系统综合症(SARS)是由一种新的冠状病毒SARS-CoV引起的。迄今为止，全球确诊的SARS病例已达8000例，其中1800人死亡，分布在30个国家。由于SARS的传播容易和严重，对公众健康构成了巨大的威胁，并造成了重大的经济损失。这项拟议研究的长期目标是开发一种有效的疫苗来预防未来的SARS疫情。虽然已针对不同的疾病开发了各种类型的疫苗，但从动物冠状病毒及其各自宿主的研究中获得的最新信息表明，最有希望的SARS疫苗是基于冠状病毒的活疫苗。然而，开发一种减毒的SARS-CoV活疫苗是一种长期的方法，其结果是不可预测的。此前，P.I.分离出一种与急性轻度腹泻有关的人类肠道冠状病毒(HECoV)，但没有其他严重的临床症状。根据普通黏膜免疫系统的原理，口服免疫的抗原刺激在诱导对呼吸道病原体的免疫方面通常是非常有效的。因此，P.I.建议(I)开发表达SARS-CoV刺突蛋白的重组人肠道冠状病毒作为SARS疫苗，以及(Ii)对重组冠状病毒的生物学特性进行鉴定。这些研究可以在建议的短时间内完成，并将提供有关重组冠状病毒作为表达载体和SARS候选活疫苗的用途的关键信息。它们将促进未来在动物和人类身上进行临床试验。这样的重组系统不仅对SARS疫苗的开发具有重要意义，而且可能为艾滋病等其他严重传染病的疫苗开发提供潜在的途径。为研究SARS冠状病毒的致病机制和免疫机制提供了有力的分子工具。这项研究的实际影响无疑是巨大的。因此，这项研究代表了R21机制的探索性性质。

DESCRIPTION (provided by applicant): The current epidemic of the severe acute respiratory syndrome (SARS) is caused by a novel coronavirus, SARS-CoV. To date, the global confirmed SARS cases have reached >8,000 with L800 deaths in 30 countries. With an ease of transmission and severity of the disease, SARS poses a great threat to public health and causes significant economic loss. The long-term goal of this proposed research is to develop an efficacious vaccine for preventing future SARS epidemic. While various types of vaccines have been developed for different illnesses, current information obtained from studies on animal coronaviruses and their respective hosts suggests that the most promising vaccine for SARS would be a coronavirus-based live vaccine. However, the development of an attenuated, live SARS-CoV vaccine is a long-term approach with an unpredictable outcome. Previously, the P.I. has isolated a human enteric coronavirus (HECoV) associated with acute, mild diarrhea but with no other severe clinical symptoms. Based on the tenet of a common mucosal immune system, antigenic stimulation by oral immunization is usually very effective in inducing immunity to respiratory pathogens. Therefore, the P.I. proposes (i) to develop a recombinant human enteric coronavirus expressing the spike protein of the SARS-CoV as a vaccine for SARS, and (ii) to characterize the biological properties of the recombinant coronavirus. These studies can be accomplished within the proposed, short period of time and will provide crucial information about the utility of the recombinant coronavirus as an expression vector and as a candidate live vaccine for SARS. They will facilitate future clinical trials in animals and humans. Such a recombinant system will not only be important for the development of SARS vaccine but may provide potential avenues for the development of vaccines for other severe infectious diseases such as AIDS. It also provides a powerful molecular tool for studying pathogenesis and immunity of SARS-CoV. The practical impact of this research will be undoubtedly enormous. This research thus represents the exploratory nature of the R21 mechanism.