Development of Proteosome-adjuvanted nasal SARS vaccines

蛋白酶体佐剂鼻SARS疫苗的研制

• 批准号: 6845794
• 负责人: DAVID R BURT
• 金额: $ 560万
• 依托单位: ID BIOMEDICAL CORPORATION OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845794
• 关键词: Baculoviridae; SARS virus; antigen antibody reaction; biological models; biotechnology; clinical research; clinical trial phase I; cooperative study; emerging infectious disease; ferrets; human subject; immunoglobulin A; immunoglobulin G; immunomodulators; inhalation drug administration; laboratory mouse; macromolecule; mucosal immunity; patient oriented research; proteasome; protein structure; severe acute respiratory syndrome; toxicology; vaccine development; vaccine evaluation; viral vaccines; virus protein

DESCRIPTION (provided by applicant): 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 nave 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.

描述（由申请人提供）：严重急性呼吸系统综合症 (SARS)，目前已知由 SARS 冠状病毒 (SARS-CoV) 引起，于 2002 年在中国出现，导致全球 8,000 多例呼吸道疾病病例和 774 人死亡-宽的。该病毒于 2004 年在中国重新出现。SARS 的死亡率很高（60 岁以上人群死亡率超过 50%，年轻人死亡率超过 10%），而且世界上大多数人对这种病毒的免疫能力尚不成熟。 SARS 冠状病毒凸显了 SARS 大流行可能对人类发病率和死亡率造成的潜在破坏性影响。除了严格的患者隔离外，目前尚无有效的治疗方法来预防SARS的传播。然而，由于 SARS 是由呼吸道病毒引起的，因此疫苗接种提供了控制该疾病的潜在方法。通过粘膜途径进行疫苗接种可以在呼吸道中产生保护性 slgA 并在血清中产生 IgG，这是一个特别有吸引力的目标。该项目的目的是开发一种经鼻给药的亚单位疫苗来预防人类SARS。 Protollin 是一种有效的粘膜佐剂，经鼻给药时可诱导保护性粘膜和全身抗体反应。 Protollin 在人类中是安全且耐受性良好的，并且已被证明可以佐剂来自各种病原体的多种抗原。在这项研究中，将首先测试表达为杆状病毒蛋白的 Protollin 佐剂 SARS-CoV Spike 蛋白在小鼠中的免疫原性。将在雪貂攻击模型中进一步检查在免疫动物的血清中诱导最佳水平的 SARS 病毒中和活​​性的制剂，以评估其防止 SARS 病毒感染的能力。随后将在 GLP 毒性研究中测试候选 Protollin SARS S 蛋白疫苗的安全性。一旦安全性得到证明，该疫苗将按照 GMP 生产，并在人体 I 期临床试验中评估安全性和免疫原性。目标是快速启动临床开发，以支持基于 Protollin 的 SARS 鼻亚单位疫苗的许可。