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

优化 SARS-CoV-2 疫苗失败的多疾病患者群体的疫苗功效 (OCTAVE-DUO)

• 批准号: MR/W020653/1
• 负责人: Iain McInnes
• 金额: $ 143.03万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW020653%2F1
• 关键词: Optimising; Vaccine; Efficacy; Multi; Disease

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.

目前为 SARs-Cov-2 提供免疫保护的疫苗接种策略是基于健康人群的研究结果。然而，疫苗接种后产生保护性免疫反应的能力可能受到许多因素的影响，包括潜在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 (OCTAVE) 正在评估 COVID-19 疫苗接种对以下患者的效果：(i) 免疫介导的炎症性疾病，(ii) 肝脏/胃肠道疾病，(iii) 肾衰竭，(iv) 实体癌或血癌，(v) 实体器官移植，以及 (vi) 接受造血干细胞移植 (HSCT) 或嵌合细胞移植的患者 抗原受体 T 细胞 (CAR-T) 或抗体缺陷。我们发现，大约 30% 的人在接受标准疫苗接种方案后，免疫反应较低或无法检测到。现在的问题是，向这一弱势群体提供额外的疫苗剂量是否可以激发足够的免疫反应，为他们提供免受 SARs-CoV-2 感染所需的基本保护。 为了解决这个问题，我们将研究现有的 OCTAVE 队列，并询问给予额外剂量的原始疫苗或替代疫苗作为“加强”是否可以推动那些对两剂疫苗没有产生保护性反应的人产生保护性反应。额外剂量的理由得到了自然感染后疫苗接种免疫原性增强（自然第三剂）的证据支持，并且该策略与其他疫苗（例如疫苗）的成功使用也得到了支持。血液透析患者的乙型肝炎。在增加疫苗接种剂量的同时，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重新接种疫苗中受益。将使用一系列已在 OCTAVE 研究中得到验证的最先进的检测方法。总之，这项研究将产生重要信息，为英国卫生和政府在当前大流行期间的疫苗接种政策提供信息。它还将探索高危人群疫苗接种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。

项目成果

SARS-CoV-2 vaccine responses in patients with conditions leading to diminished immune capacity - The OCTAVE and OCTAVE-DUO Trials. (Mini oral presentation)

患有导致免疫能力下降的患者的 SARS-CoV-2 疫苗反应 - OCTAVE 和 OCTAVE-DUO 试验。

• 发表时间: 2022
• 作者: Thushan De Silva

Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019.

• DOI: 10.1016/s0140-6736(22)02185-7
• 发表时间: 2022-12-17
• 期刊: Lancet (London, England)

T cell immune memory after covid-19 and vaccination.

• DOI: 10.1136/bmjmed-2022-000468
• 发表时间: 2023
• 期刊: BMJ medicine
• 作者: Wang, Lulu;Nicols, Alex;Turtle, Lance;Richter, Alex;Duncan, Christopher J. A.;Dunachie, Susanna J.;Klenerman, Paul;Payne, Rebecca P.
• 通讯作者: Payne, Rebecca P.