MVA based SARS-CoV-2 vaccines

这项建议的总体目标是开发有效的预防性疫苗，以对抗新型SARS 冠状病毒-2（SARS-CoV-2）感染最近已成为全球大流行病。SARS-CoV-2已经感染了超过12万人，超过4000人死于COVID-19， 由SARS-CoV-2引起。因此，迫切需要开发一种能够快速诱导免疫应答的疫苗。 抗病毒免疫，预防感染。先前来自其他相关冠状病毒感染（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 有效防止感染。因此，本建议的主要目标是开发一种改良的安卡拉牛痘（MVA） 基于表达SARS-CoV-2刺突蛋白的疫苗，以产生快速和强中和抗体 在全身和粘膜隔室的反应。基于MVA的疫苗有几个优点 包括其极好安全性，单剂量MVA疫苗接种可提供针对多种 病毒感染，包括SARS-CoV，MERS，Zika和埃博拉病毒。这一提议的一个新方面是，我们 将比较不同形式的刺突蛋白的免疫原性和保护能力，目的是 诱导抗SARS-CoV-2和SARS-CoV的中和抗体。这项建议有两个具体目标。 目的1的目标是产生MVA疫苗并表征小鼠中的抗刺突抗体应答。我们 还将比较胃肠外（i.m.）vs粘膜（鼻内）接种，以确定诱导的最佳途径 粘膜抗体反应。目标2的目的是评估基于MVA的SARS-CoV-2疫苗的保护效力。迫切需要开发和表征小动物模型， 评估疫苗对SARS-CoV 2的有效性。小鼠作为一个很好的模型系统，不仅 了解对相关SARS病毒的免疫力，也用于评估疫苗和抗病毒疗法。在这 目的是，我们将开发和表征SARS-CoV 2感染的小鼠模型，并使用该模型来测试 我们基于MVA的候选疫苗的保护效力。这些研究的完成不仅将提供 SARS-CoV 2感染的小鼠模型，而且还开发针对SARS-CoV 2的候选疫苗。

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 viruse. 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-CoV2. 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-CoV2 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-CoV2 infection but also develop vaccine candidates against SARS-CoV2.