A Single-dose DNA vaccine platform to safely induce protective immunity against Zika

我们的团队已经开发出一种快速，低成本和有效的DNA疫苗，可以刺激小鼠对COVID-19及其变体的有效免疫反应。这已进入人体试验，旨在证明安全有效的疫苗接种和免疫增强剂部署。这种方法也可用于开发安全有效的疫苗，以预防登革热和寨卡等黄病毒感染。像其他正在开发的寨卡疫苗一样，我们的疫苗将帮助身体产生抗体，阻止寨卡病毒进入细胞并导致人感染。这种疫苗与其他方法的不同之处在于，它还将刺激免疫系统产生特殊的T细胞，这些T细胞可以识别并杀死可能已感染病毒的细胞。这些T细胞也将比抗体在体内停留的时间更长，并在未来感染的情况下存在。拟议的寨卡疫苗将作为几种变体产生，这些变体针对病毒产生的非结构蛋白，或使用DNA作为模板的缺陷完整病毒。大多数试验中的DNA疫苗使用轻微的电击（电穿孔）或压力来增加递送的DNA的功效。虽然这种方法有效，但它需要昂贵的设备来输送疫苗。当数百万健康受试者需要接种疫苗时，如在COVID-19大流行期间，或在未来可能发生的寨卡等黄病毒大流行中，这是不切实际的。为了克服这个问题，我们开发了一个优雅的系统，可以通过简单的注射来提供DNA。这项技术被称为GET，我们已经修改了这一系统，以提高使用聚合物化学接种COVID-19疫苗的活性。我们的目标是通过给小鼠接种疫苗来测试我们设计的新寨卡疫苗，并在项目结束时定位，使我们和我们的巴西合作者能够快速开始人体试验，并在巴西验证我们的新DNA方法，巴西是一个受寨卡影响严重的国家。这一战略可能对发展中国家和全球的流行病预防产生变革性影响。重要的是，这将使一种新的DNA疫苗被用于许多其他疾病，使我们能够更好地为下一次大流行做好准备。

Our team has already developed a fast, low cost and effective DNA vaccine that stimulates potent immune responses for COVID-19 and its variants in mice. This has entered human trials aiming to demonstrate safe and effective vaccination and immune booster deployment. This approach can also be used to develop a safe and effective vaccine to prevent infection by flaviviruses such Dengue and Zika. Like other Zika vaccines being developed, ours will help the body to make antibodies to stop the Zika virus entering cells and causing the person to become infected. What makes this vaccine different from other approaches is that it will also stimulate the immune system to make special T cells that can recognise and kill cells that may have been infected with the virus. These T cells will also remain in the body longer than antibodies and be there in case of future infections. The proposed Zika vaccine will be generated as several variants targeting either a non-structural protein made by the virus, or a defective intact virus using DNA as the template. Most DNA vaccines under trial are administered using mild electric shock (electroporation) or pressure to increase efficacy of the DNA delivered. Although this approach works it requires an expensive device to deliver the vaccine. This is not practical when millions of healthy subjects will need to be immunised, as during the COVID-19 pandemic, or in potential future pandemics of flaviviruses like Zika. To overcome this problem, we have developed an elegant system to allow the DNA to be given by simple injection. This technology is called GET and we have modified this system to enhance the activity of vaccination for COVID-19 using polymer chemistry. Our aim is to test the new Zika vaccines we engineer by vaccinating mice and at the end of the project be positioned to allow us and our Brazilian collaborators to start human trials quickly and validate our novel DNA approach in Brazil, a country significantly affected by Zika. This strategy could have a transformative impact on pandemic prevention in the developing world and globally. Importantly this will allow a new class of DNA vaccines to be employed for many other diseases allowing us to be better prepared for the next pandemic.