Optimising Vaccine Efficacy in Multi-Disease Patient Cohorts with SARS-CoV-2 vaccine failure (OCTAVE-DUO)

目前为SARS-CoV-2提供免疫保护的疫苗接种策略是基于在健康队列中的发现。然而，接种疫苗后产生保护性免疫反应的能力可能会受到许多因素的影响，包括潜在的疾病以及人们正在接受的疾病治疗。我们目前的多中心研究(OCTIVE)正在评估免疫介导性炎症性疾病，(Ii)肝脏/胃肠道疾病，(Iii)肾功能衰竭，(Iv)实体或血癌，(V)实体器官移植，以及(Vi)接受造血干细胞移植或嵌合抗原受体T细胞(CAR-T)或抗体缺乏的患者的新冠肺炎疫苗接种效果。我们发现，大约30%的这些人在接受标准疫苗接种后免疫应答较低或检测不到。现在的问题是，向这一脆弱人群提供额外的疫苗剂量是否能够推动足够的免疫反应，为他们提供必要的保护，使他们免受SARS-CoV-2感染。为了解决这个问题，我们将研究我们现有的八度队列，并将询问额外剂量的原始或替代疫苗是否可以促进那些对两剂疫苗没有保护性反应的人产生保护性反应。有证据表明，在自然感染(自然第3剂)后接种疫苗可增强免疫原性，并将这一策略成功地用于其他疫苗，例如血液透析患者的乙肝疫苗，这支持了增加剂量的理由。在额外接种疫苗的同时，我们将采集血液样本并进行深入研究，看看免疫反应的任何特征是否可以预测哪些患者将从再次接种疫苗中受益。将使用一系列已经在八度研究中得到验证的最先进的分析方法。总而言之，这项研究将产生关键信息，为英国卫生和政府在正在进行的大流行期间制定疫苗接种政策提供信息。它还将探索高危人群疫苗免疫原性背后的科学，这将为未来的疫苗接种政策提供信息。

The current vaccination strategy to provide immunological protection to SARs-Cov-2 is based on findings in healthy cohorts. The ability to generate a protective immune response after vaccination can, however, be influenced by many factors including underlying disease, and the treatment people are receiving for their disease. Our current multi-centre study (OCTAVE) is evaluating how well COVID-19 vaccination works in people with (i) immune mediated inflammatory diseases, (ii) hepatic/gastrointestinal disease, (iii) renal failure, (iv) solid or blood cancers, (v) solid organ transplant, and (vi) patients who have received haematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T cells (CAR-T) or antibody deficiency.We have found that approximately 30% of these people mount either a low or undetectable immune response after undergoing standard vaccination regimes. The question now is whether giving extra vaccine doses to this vulnerable population can drive a sufficient immune response to provide the essential protection they need from SARs-CoV-2 infection. To address this, we will study our existing OCTAVE cohort and will ask whether giving an extra dose of the original or an alternative vaccine as a "boost" can drive a protective response in those who did not make a protective response to two doses. The rationale for an additional dose is supported by evidence for enhanced immunogenicity of vaccination following natural infection (a natural 3rd dose) and also the successful use of this strategy with other vaccines e.g. hepatitis B in haemodialysis patients. In parallel with an extra vaccination dose, we will take blood samples and conduct an in-depth study to see if any features of the immune response can predict which patients will benefit from re-vaccination. A range of state-of-the-art assays that have already been validated in the OCTAVE study will be used. In summary, this study will generate critical information that will inform UK health and government vaccination policies during the ongoing pandemic. It will also explore the science behind vaccination immunogenicity in at risk groups that will inform vaccination policy going forward.