MVA based SARS-CoV-2 vaccines

基于 MVA 的 SARS-CoV-2 疫苗

• 批准号: 10265756
• 负责人: Rama Rao Amara
• 金额: $ 18.77万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265756
• 关键词: AIDS/HIV problem; Adjuvant; Affinity; Agonist; Amino Acids; Animal Model; Animals; Antibodies; Antibody Formation; Antibody Response; Antigens; Autologous; Avidity; Binding; Cavia; Cells; Complex; Development; Enterotoxins; Epitopes; Failure; Formulation; Goals; HIV; HIV Envelope Protein gp120; HIV Infections; HIV Vaccine Trials Network; HIV vaccine; HIV-1; Human; Humoral Immunities; Immune; Immunization; Infection prevention; Laboratories; Link; Macaca; Macaca mulatta; Modality; Modeling; Modified Vaccinia Virus Ankara; Molecular; Molecular Conformation; Mosaicism; Mucous Membrane; Mutation; Oryctolagus cuniculus; Pathogenicity; Periodicity; Proteins; Regimen; Resistance; SIV; Secondary Immunization; Specificity; TLR7 gene; TNFSF5 gene; Testing; Thailand; Time; Vaccination; Vaccines; Virus; Virus Diseases; aluminum sulfate; base; cartilage matrix protein; cross reactivity; design; disulfide bond; efficacy trial; env Gene Products; immunogenicity; improved; mutant; nanoparticle; neutralizing antibody; nonhuman primate; novel; novel vaccines; prevent; protective efficacy; response; scaffold; simian human immunodeficiency virus; vaccine efficacy

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.

该提案的总体目标是针对新型SARS开发有效的预防性疫苗 冠状病毒-2（SARS-COV-2）感染最近已成为全球大流行。 SARS-COV-2已经感染了120,000多人，4000多人死于Covid-19，一种疾病 由SARS-COV-2引起。因此，迫切需要开发可以快速诱导的疫苗 抗病毒免疫并防止感染。来自其他相关冠状病毒感染（例如SARS-COV和MERS-COV）的先前数据表明，针对尖峰蛋白的强中和抗体反应可以 有效防止感染。因此，该提案的主要目标是开发修改后的Ankara（MVA） 表达SARS-COV-2尖峰蛋白以产生快速而强中和抗体的疫苗 全身和粘膜室的反应。基于MVA的疫苗有几个优势 其中包括其出色的安全性和一剂MVA疫苗接种可以为多个 病毒感染，包括SARS-COV，MERS，Zika和Ebola Viruse。该提议的一个新颖方面是我们 将比较不同形式的尖峰蛋白的免疫原性和保护能力 诱导针对SARS-COV-2和SARS-COV的中和抗体。该提议有两个具体的目标。 AIM 1的目的是生成MVA疫苗并表征小鼠中抗尖峰抗体反应。我们 还将比较肠胃外（I.M.）与粘膜（鼻内）疫苗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疫苗的保护功效。有一个紧急且未满足的需要开发和表征小动物模型 评估针对SARS-COV2的疫苗功效。小鼠不仅是一个出色的模型系统 了解对相关SARS病毒的免疫力，还可以评估疫苗和抗病毒治疗剂。在这个 目的，我们将开发并表征SARS-COV2感染的鼠标模型，并使用此模型测试 我们基于MVA的疫苗候选物的保护功效。这些研究的完成不仅将提供 用于SARS-COV2感染的小鼠模型，但也会开发针对SARS-COV2的疫苗候选物。