Development and validation of an easily accessible, whole-blood test for the assessment of natural and vaccine-induced T-cell responses to SARS-CoV-2

随着英国SARS-CoV-2疫苗接种计划的作用顺利进行，人们开始质疑这些疫苗的有效性和寿命。接种疫苗的目的是产生强大的、长期的免疫反应，从而防止更广泛人群的再次感染。抗体的产生是身体对抗病毒感染的一种方式。此外，长期保护也来自t细胞，它在控制和根除病毒方面起着关键作用。然而，人们对接种疫苗产生的t细胞反应的寿命知之甚少。因此，我们的目标是开发一种新的t细胞测试，这将有助于解决一些基本的研究问题，如免疫力是否会在规定的时间后开始减弱，这些反应的强度或寿命是否会在更广泛的人群中的弱势群体中观察到差异？从历史上看，测量t细胞对病毒的免疫反应被证明是一项比测量病毒特异性抗体更困难的任务，因为它们既费力又需要复杂的技术诀窍。在这里，我们建议使用一种新的系统，旨在克服与传统方法相关的技术障碍和时间限制。我们的目标是在从患者身上获取样本方面进行颠覆性创新，通过验证新的血液采集方法来提高测试的可及性，这将取消从训练有素的采血师那里抽取静脉血的要求。从这个血液样本中，我们将刺激样本中发现的t细胞，并测量细胞因子的后续产生——细胞因子是免疫系统的关键组成部分，有助于根除病毒。我们的目的是在临床环境中试验该测试，其中我们将测量临床认为易受感染或最“有风险”再次感染的个体队列中的t细胞反应。这些患者包括艾滋病毒感染者、免疫功能低下患者和疫苗无应答者。我们的测试将测量t细胞随时间的反应，以评估t细胞免疫是否在这些人群中衰退得更快。如果成功，我们的目标是将该测试商业化，并在更大范围内提供。通过与学术界病毒学领域的专家以及NHS经验丰富的临床医生和全科医生的合作，我们有信心提供这种创新的、高度分类的t细胞测试。

With the role out of the SARS-CoV-2 vaccination programme here in the UK well underway, questions around the efficacy and the longevity of these vaccines are beginning to be asked. The aim of vaccinations is to produce a robust, long lived immune response, thus preventing re-infection in the wider population. The production of antibodies is one way the body can fight viral infections. Additionally, long-term protection also comes from T-cells, which play a critical role in controlling and eradicating the virus. However, little is known about the longevity of the T-cell response generated from vaccinations. Therefore, our goal is to develop a novel T-cell test that will contribute to addressing some fundamental research questions such as if immunity will begin to wane after a defined time, and will differences in magnitude or longevity of these response be observed in vulnerable cohorts within the wider population?Historically, measuring T-cell immune responses to viruses has proved a more difficult task than measuring virus-specific antibodies as they are laborious and require complex technical know-how. Here, we propose using a novel system that is designed to overcome the technical hurdles and time constraints associated with traditional methods. We aim to make disruptive innovations in terms of obtaining samples from patients, leading to improved accessibility to the test by validating novel methods of blood collection that would abrogate the requirement for venous blood draw from a trained phlebotomist. From this one sample of blood, we would then stimulate T-cells found within that sample and measure the subsequent production of cytokines - proteins that form a crucial part of the immune system that aids with eradicating the virus. Our intention is to trial the test in a clinical setting, wherein we will measure T-cell responses in cohorts of individuals deemed to be clinically vulnerable or most 'at risk' from re-infection. These will include HIV-infected patients, immunocompromised patients, and vaccine non-responders. Our test would measure T-cell responses over time to assess if T-cell immunity wanes faster in these cohorts of individuals. If successful, our ambition is to be able to commercialise the test and offer it on a wider scale.In collaboration with experts in the virology field from academia and experienced clinicians and GPs from the NHS, we are confident on delivering this innovative and highly sort after T-cell test.