MVA based SARS-CoV-2 vaccines

这项建议的总体目标是开发针对新型SARS的有效预防性疫苗。 冠状病毒-2(SARS-CoV-2)感染，最近在世界各地出现大流行。SARS-CoV-2已经感染了超过12万人，超过4000人死于新冠肺炎 由SARS-CoV-2引起。因此，迫切需要开发一种能够快速诱导免疫的疫苗。 抗病毒免疫，预防感染。以前来自其他相关冠状病毒感染的数据，如SARS-CoV和MERS-CoV表明，针对Spike蛋白的强大中和抗体反应可以 有效预防感染。因此，这项提议的一个主要目标是开发一种改良的安卡拉牛痘(MVA)。 表达SARS-CoV-2刺突蛋白产生快速中和抗体的疫苗 在全身和粘膜间隔中均有反应。基于MVA的疫苗有几个优点 这包括它们极佳的安全性和单剂MVA疫苗可以提供预防多发性 病毒感染包括SARS冠状病毒、MERS、寨卡病毒和埃博拉病毒。这项提议的一个新方面是，我们 将比较不同形式的Spike蛋白的免疫原性和保护能力，目标是 诱导抗SARS-CoV-2和SARS-CoV中和抗体。这项提议有两个具体目标。 目标1的目标是生产MVA疫苗，并表征小鼠的抗刺抗体反应。我们 也会比较肠外(I.M.)与黏膜(鼻腔)疫苗相比，确定最佳诱导途径 粘膜抗体反应。目标2的目的是评估基于MVA的SARS-CoV-2疫苗的保护效果。有一种迫切的和尚未得到满足的需求，即开发和表征小动物模型 SARS-CoV-2疫苗效力评价。MICE不仅是一个很好的模型系统 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：建立和鉴定SARS-CoV-2感染小鼠模型，并利用该模型对SARS-CoV-2感染小鼠模型进行实验研究。 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 一种感染SARS-CoV-2的小鼠模型，但也开发了针对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 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.