Determining the immunological basis for weakened SARS-CoV-2 vaccination outcomes

确定 SARS-CoV-2 疫苗接种效果减弱的免疫学基础

• 批准号: MR/W020556/1
• 负责人: Laura McCoy
• 金额: $ 54.17万
• 依托单位: University College London
• 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%2FW020556%2F1
• 关键词: Determining; immunological; basis; weakened; SARS

The goal of this study is to understand how effective post COVID-19 vaccine responses are and how long they last. Specifically, we will investigate this in people with compromised immune systems because early reports suggest they make very poor responses to COVID-19 vaccines. These people are often also the most at risk of severe disease if they develop COVID-19 so our work will inform future recommendations/policy on how to protect these vulnerable people. Beyond individual benefit, it is important to understand why some people make less effective vaccine responses to control the spread of the virus in the population. This is because, weak vaccine responses mean they may be more likely to catch and transmit the virus thus keeping it in circulation and potentially leading to emergence of additional variants. We will complete two aims by looking at individuals across a spectrum of immune function: healthy volunteers, people living with HIV (who have predominantly T cell deficiencies) and people with B cell malignancies (who have mainly had treatment that drastically reduces their B cell numbers). Firstly we will evaluate the vaccine responses in their blood and rank their effectiveness. We will then link this to data on how well their immune cells (B, T and NK cells in particular) are performing to understand what the immunological profile is of someone who makes a poor vaccine response. Secondly, we will attempt to understand whether some people's vaccine responses are less able to cope with variant viruses. We will do this by looking at diversity and resilience within their B cells, which make antibodies, and by examine how the T and NK cells respond to virus and cooperate to help B cells make antibody. Our findings will inform policy regarding the best frequency of variant boosters and whether a full course of vaccination or single boost is needed based on how severely a person's immune system has been compromised not based solely on their clinical diagnosis.

这项研究的目的是了解COVID-19疫苗接种后的反应有多有效以及持续多久。具体来说，我们将在免疫系统受损的人群中调查这一点，因为早期报告表明他们对COVID-19疫苗的反应非常差。如果这些人患上COVID-19，他们通常也是最有可能患上严重疾病的人，因此我们的工作将为未来关于如何保护这些脆弱人群的建议/政策提供信息。除了个人利益之外，重要的是要了解为什么有些人对控制病毒在人群中的传播的疫苗反应不那么有效。这是因为，弱的疫苗反应意味着它们可能更有可能捕获和传播病毒，从而使其保持流通，并可能导致其他变体的出现。我们将通过观察不同免疫功能的个体来完成两个目标：健康志愿者，艾滋病毒感染者（主要是T细胞缺陷）和B细胞恶性肿瘤患者（主要接受了大幅减少B细胞数量的治疗）。首先，我们将评估他们血液中的疫苗反应并对其有效性进行排名。然后，我们将把这一点与他们的免疫细胞（特别是B、T和NK细胞）的表现数据联系起来，以了解疫苗反应不佳的人的免疫学特征。其次，我们将试图了解一些人的疫苗反应是否不太能够科普变异病毒。我们将通过观察产生抗体的B细胞的多样性和弹性，以及通过检查T细胞和NK细胞如何对病毒做出反应并合作帮助B细胞产生抗体来实现这一目标。我们的研究结果将为政策提供关于变体助推器的最佳频率以及是否需要基于一个人的免疫系统受到损害的严重程度而不是仅仅基于他们的临床诊断进行完整的疫苗接种或单次助推的信息。

项目成果

Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1.

• DOI: 10.1038/s41598-023-45412-9
• 发表时间: 2023-11-03
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Alrubayyi, Aljawharah;Touizer, Emma;Hameiri-Bowen, Dan;Charlton, Bethany;Gea-Mallorqui, Ester;Hussain, Noshin;da Costa, Kelly A. S.;Ford, Rosemarie;Rees-Spear, Chloe;Fox, Thomas A.;Williams, Ian;Waters, Laura;Barber, Tristan J.;Burns, Fiona;Kinloch, Sabine;Morris, Emma;Rowland-Jones, Sarah;McCoy, Laura E.;Peppa, Dimitra
• 通讯作者: Peppa, Dimitra

Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles.

SARS-COV-2疫苗接种后与B细胞缺陷和免疫谱改变的SARS-COV-2疫苗接种后，HIV中的体液反应减弱。

• DOI: 10.1016/j.isci.2022.105862
• 发表时间: 2023-01-20
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Touizer, Emma;Alrubayyi, Aljawharah;Ford, Rosemarie;Hussain, Noshin;Gerber, Pehuen Pereyra;Shum, Hiu-Long;Rees-Spear, Chloe;Muir, Luke;Gea-Mallorqui, Ester;Kopycinski, Jakub;Jankovic, Dylan;Jeffery-Smith, Anna;Pinder, Christopher L.;Fox, Thomas A.;Williams, Ian;Mullender, Claire;Maan, Irfaan;Waters, Laura;Johnson, Margaret;Madge, Sara;Youle, Michael;Barber, Tristan J.;Burns, Fiona;Kinloch, Sabine;Rowland-Jones, Sarah;Gilson, Richard;Matheson, Nicholas J.;Morris, Emma;Peppa, Dimitra;McCoy, Laura E.
• 通讯作者: McCoy, Laura E.