MVA based SARS-CoV-2 vaccines

基于 MVA 的 SARS-CoV-2 疫苗

• 批准号: 10221340
• 负责人: Rama Rao Amara
• 金额: $ 29.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-24 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221340
• 关键词: 2019-nCoV; Animal Model; Antibodies; Antibody Affinity; Antibody Response; Antibody titer measurement; Antigens; Antiviral Agents; Autologous; Binding; Binding Sites; Biological Models; CD8-Positive T-Lymphocytes; COVID-19; Cell membrane; Coronavirus Infections; Data; Disease; Dose; Ebola virus; Epitopes; Goals; HIV; Human; Immunity; Immunization; Immunize; Individual; Infection; Infection prevention; Length; Measures; Middle East Respiratory Syndrome Coronavirus; Modeling; Modified Vaccinia Virus Ankara; Mucous Membrane; Mus; Preventive vaccine; Proteins; Recombinants; Route; SARS coronavirus; Safety; Surface; T cell response; Testing; Therapeutic; Transgenic Mice; Vaccination; Vaccines; Virion; Virus; Virus Diseases; Virus-like particle; Zika Virus; antiviral immunity; base; cross reactivity; immunogenicity; monomer; mouse model; neutralizing antibody; novel; pandemic disease; protective efficacy; receptor binding; response; vaccine candidate; vaccine development; vaccine efficacy; vaccine trial; vector

The overall goal of this proposal is to develop effective prophylactic vaccines against the novel SARS Coronavirus-2 (SARS-CoV-2) infection that has recently emerged as a pandemic across the world. The SARS-CoV-2 has already infected more than 120,000 people and over 4000 people died due to COVID-19, a disease caused by SARS-CoV-2. Thus, there is an urgent need for the development of a vaccine that can rapidly induce anti-viral immunity and prevent infection. Previous data from other related coronavirus infections such as SARS-CoV and MERS-CoV demonstrate that a strong neutralizing antibody response against the spike protein can effectively prevent infection. Thus, a primary goal of this proposal is to develop a modified vaccinia Ankara (MVA) based vaccine that expresses SARS-CoV-2 spike protein to generate a rapid and strong neutralizing antibody response both in systemic and mucosal compartments. There are several advantages to MVA based vaccines that include their excellent safety and a single dose of MVA vaccination can provide protection against multiple virus infections including SARS-CoV, MERS, Zika and Ebola virus. A novel aspect of this proposal is that we will compare the immunogenicity and protective ability of different forms of the spike protein with a goal of inducing neutralizing antibodies against both SARS-CoV-2 and SARS-CoV. This proposal has two specific aims. The goal of Aim 1 is to generate MVA vaccines and characterizing the anti-spike antibody response in mice. We will also compare parenteral (i.m.) vs mucosal (intranasal) vaccinations to determine the best route for inducing mucosal antibody response. The goal of Aim 2 is to evaluate the protective efficacy of the MVA-based SARS-CoV-2 vaccines. There is an urgent and unmet need to develop and characterize small animal models for evaluating vaccine efficacy against SARS-CoV-2. Mice have served as an excellent model system to not only understand immunity to the related SARS virus but also for evaluating vaccines and antiviral therapeutics. In this Aim, we will develop and characterize a mouse model of SARS-CoV-2 infection and use this model to test the protective efficacy of our MVA-based vaccine candidates. The completion of these studies will not only provide a mouse model for SARS-CoV-2 infection but also develop vaccine candidates against SARS-CoV-2.

该提案的总体目标是开发针对新型 SARS 的有效预防疫苗 冠状病毒 2 (SARS-CoV-2) 感染最近在全球范围内流行。 SARS-CoV-2 已感染超过 120,000 人，超过 4000 人因 COVID-19 死亡 由 SARS-CoV-2 引起。因此，迫切需要开发一种能够快速诱导的疫苗。 抗病毒免疫力并预防感染。先前来自其他相关冠状病毒感染（例如 SARS-CoV 和 MERS-CoV）的数据表明，针对刺突蛋白的强中和抗体反应可以 有效预防感染。因此，该提案的主要目标是开发改良的安卡拉牛痘 (MVA) 基于表达 SARS-CoV-2 刺突蛋白的疫苗，可产生快速而强的中和抗体 全身和粘膜室的反应。基于 MVA 的疫苗有几个优点 其卓越的安全性以及单剂 MVA 疫苗接种可以提供针对多种疾病的保护 病毒感染，包括 SARS-CoV、MERS、寨卡病毒和埃博拉病毒。该提案的一个新颖之处是我们 将比较不同形式的刺突蛋白的免疫原性和保护能力，目标是 诱导针对 SARS-CoV-2 和 SARS-CoV 的中和抗体。该提案有两个具体目标。 目标 1 的目标是生成 MVA 疫苗并表征小鼠中的抗尖峰抗体反应。我们 还将比较肠胃外（肌内）疫苗接种与粘膜（鼻内）疫苗接种，以确定最佳诱导途径 粘膜抗体反应。目标 2 的目标是评估基于 MVA 的 SARS-CoV-2 疫苗的保护功效。开发和表征小动物模型的迫切需求尚未得到满足 评估疫苗针对 SARS-CoV-2 的功效。小鼠作为一个优秀的模型系统，不仅 了解对相关 SARS 病毒的免疫力，还可以评估疫苗和抗病毒疗法。在这个 目标是，我们将开发并表征 SARS-CoV-2 感染的小鼠模型，并使用该模型来测试 我们基于 MVA 的候选疫苗的保护功效。这些研究的完成不仅将提供 SARS-CoV-2 感染的小鼠模型，同时还开发针对 SARS-CoV-2 的候选疫苗。