Toward a protective Covid-19 vaccine utilizing an established vector platform

利用已建立的载体平台开发保护性 Covid-19 疫苗

• 批准号: 10170820
• 负责人: Matthias Johannes Schnell
• 金额: $ 42.9万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-16 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170820
• 关键词: 2019-nCoV; Adjuvant; Animal Model; Animals; Antibodies; Antibody Response; Antigens; Antiviral Agents; Biology; COVID-19; COVID-19 vaccine; Cell Line; Cessation of life; China; Chiroptera; Communities; Complementary DNA; Coronavirus; Coronavirus Infections; Development; Disease; Disease Outbreaks; Emerging Communicable Diseases; Epidemic; Epidemiology; Goals; Hamsters; Human; Immune response; Immunity; Immunization; Infection; Integration Host Factors; Investigation; Laboratories; Language; Mammals; Membrane; Methods; Middle East Respiratory Syndrome Coronavirus; Modeling; Mus; Pathogenesis; Pathology; Patient Care; Predisposition; Proteins; Rabies virus; Recombinant Proteins; Recombinants; Role; SARS coronavirus; Safety; Severe Acute Respiratory Syndrome; System; Testing; Therapeutic; Vaccines; Viral; Virion; Virus; Virus Diseases; Virus Replication; Work; base; global health; immunogenicity; mouse model; novel; novel coronavirus; novel vaccines; preclinical study; response; reverse genetics; scale up; transmission process; vaccination strategy; vaccine candidate; vaccine development; vector; vector-based vaccine

Abstract The recently emerged coronavirus SARS-CoV-2, the causative agent of COVID-19, is rapidly spreading in the world with over 4,8 million cases, and 320,000 deaths as of May 16, 2020. This novel coronavirus is thought to have emerged from a live animal market in Wuhan, China. It has quickly spread in the community with large clusters of human-to-human transmission. Sequencing of several isolates has determined that the most closely related strains are SARS-like bat coronavirus lineages. The susceptibility of SARS-CoV-2 to anti-viral compounds, its ability to replicate in cell lines or host factors regulating its replication are all currently unknown. Importantly, there are no therapeutics available to treat the virus, although investigational studies are underway. Modelling of the current outbreak suggests that the virus could infect >1 billion people and become a yearly epidemic. Identifying people who have developed antibodies is important for the epidemiology as well as patient care. With the exponentially expounding threat of SARS-CoV-2 to global health, a vaccine is desperately needed. Herein we propose the development of a novel, highly efficacious and safe COVID-19 vaccine with facile scale up potential. Our proposal uses a rabies virus-based vector that has proven to be an efficient vaccine against emerging and re-emerging infectious diseases. We have demonstrated that inactivated rabies virus particles containing the coronavirus (CoV) spike S1 protein induce potent immune responses and provide protection in animal systems against Middle Eastern Respiratory Syndrome coronavirus (MERS) and Severe Acute Respiratory Syndrome (SARS) coronavirus, both of which are highly related to SARS-CoV-2. A similar vaccine entitled CoraVax™ is available and herein we propose to analyze CoraVax™ immunogenicity in mice as well as its abilty to protect in a hamster model.

抽象的 最近出现的冠状病毒 SARS-CoV-2（COVID-19 的病原体）正在全球迅速传播。 截至 2020 年 5 月 16 日，全球已有超过 480 万病例，32 万人死亡。这种新型冠状病毒被认为 来自中国武汉的活体动物市场。已在社区迅速传播，规模较大 人与人之间的聚集性传播。对几个分离株的测序已确定最接近的 相关毒株是类似SARS的蝙蝠冠状病毒谱系。 SARS-CoV-2对抗病毒药物的敏感性 化合物、其在细胞系中复制的能力或调节其复制的宿主因素目前都是未知的。 重要的是，尽管调查研究正在进行中，但尚无可用于治疗该病毒的疗法。 当前疫情爆发的模型表明，该病毒可能感染超过 10 亿人，并成为每年一次的流行病。 流行性。识别产生抗体的人对于流行病学和患者都很重要 关心。 随着 SARS-CoV-2 对全球健康的威胁呈指数级增长，迫切需要疫苗。 在此，我们建议开发一种新型、高效、安全且易于规模化的 COVID-19 疫苗 提高潜力。我们的建议使用基于狂犬病病毒的载体，该载体已被证明是一种有效的疫苗 新出现和重新出现的传染病。我们已经证明灭活的狂犬病病毒颗粒 含有冠状病毒 (CoV) 刺突 S1 蛋白的药物可诱导有效的免疫反应并提供保护 动物系统对抗中东呼吸综合征冠状病毒（MERS）和重症急性 呼吸综合征（SARS）冠状病毒，两者都与 SARS-CoV-2 高度相关。类似的疫苗 标题为 CoraVax™ 的产品已上市，在此我们建议分析 CoraVax™ 在小鼠中的免疫原性以及 它在仓鼠模型中的保护能力。

项目成果

SARS-CoV-2 vaccines - the biggest medical research project of the 21st century.

• DOI: 10.1016/j.coviro.2021.04.008
• 发表时间: 2021-08
• 期刊: Current opinion in virology
• 影响因子: 5.9
• 作者: Kurup D;Schnell MJ
• 通讯作者: Schnell MJ

Current vaccine strategies against SARS-CoV-2: Promises and challenges.

• DOI: 10.1016/j.jaci.2022.05.008
• 发表时间: 2022-07
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
• 影响因子: 14.2
• 作者: Kurup, Drishya;Myers, Jacob;Schnell, Matthias J.
• 通讯作者: Schnell, Matthias J.

A Single Dose of the Deactivated Rabies-Virus Vectored COVID-19 Vaccine, CORAVAX, Is Highly Efficacious and Alleviates Lung Inflammation in the Hamster Model.

单剂量停用的狂犬病 - 病毒载体vected-Covid-19疫苗Coravax高效，可以减轻仓鼠模型中的肺部炎症。

• DOI: 10.3390/v14061126
• 发表时间: 2022-05-24
• 期刊: Viruses

Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity.

• DOI: 10.1038/s41541-022-00532-7
• 发表时间: 2022-09-23
• 期刊: NPJ vaccines
• 影响因子: 9.2