Durability of immune responses to SARS-CoV-2 infection in the context of HIV-infection, aging and cross-reactive immune responses.

HIV 感染、衰老和交叉反应免疫反应背景下对 SARS-CoV-2 感染的免疫反应的持久性。

• 批准号: 10188882
• 负责人: Beth Deirdre Jamieson-Karavodin
• 金额: $ 19.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188882
• 关键词: 2019-nCoV; Address; Adult; Age; Aging; Animals; Antibodies; Antibody Response; CD8-Positive T-Lymphocytes; CD8B1 gene; COVID-19; Cells; Coronavirus; Data; Data Collection; Deltastab; Dengue; Disease Progression; Dose; Elderly; Ensure; Exposure to; Frequencies; Future; Glean; Goals; Gold; HIV; HIV Infections; HIV Seronegativity; Health Policy; Human; IgG(T); Immune; Immune response; Immune system; Immunity; Immunoglobulin G; Individual; Infection; Kinetics; Literature; Lower Respiratory Tract Infection; Lung; Measures; Medical; Morbidity - disease rate; Nature; Participant; Pathogenesis; Phenotype; Policies; Population; Populations at Risk; Positioning Attribute; Prevalence; Production; Protocols documentation; Public Health; Public Policy; Reporting; Research; Risk; SARS coronavirus; Severe Acute Respiratory Syndrome; Severity of illness; T cell response; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Time; Vaccination; Vaccines; Viral Pathogenesis; Virus; Virus Diseases; Vulnerable Populations; base; case control; cross reactivity; cytokine; design; development policy; influenza virus vaccine; insight; mortality; pandemic disease; pathogen; peer; research clinical testing; response; sample collection; secondary infection; senescence; sex; transmission process; vaccine development; vaccine trial; viral transmission

SUMMARY/ABSTRACT There is almost no information about the immune response to SARS-CoV-2, the causative agent of COVID 19. What little we know has either emerged in real time during the 2020 pandemic or has been gleaned from a handful of studies on SARS-CoV-1. The pressing question at the moment is whether individuals who have recovered from infection with SARS-CoV-2 will have durable immune responses that are protective against reinfection and recurring illness. Current efforts to address this question are largely focused on antibody responses as they are not only easier to measure than T-cell responses, but antibodies provide the first line of adaptive immune protection and can often neutralize a pathogen before widespread infection occurs. However, T-cells are also essential in providing protection against secondary infection and T-cell memory is ideally elicited by vaccination. Understanding the T-cell response, both the quality and durability to natural infection with SARS-CoV-2, will not only provide insight into the pathogenesis of SARS-CoV-2, but will be important for vaccine development. However, HIV-infected individuals, with immune system deficits, represent a highly at-risk population for morbidity and mortality from SARS-CoV-2. It is therefore critical to understand how this population responds to this virus and to vaccination against SARS-CoV-2. To investigate this, we will characterize IgG as well as CD4+ and CD8+ T-cell subsets in the MWCCS participants who have had confirmed infection with SARS-CoV-2, either through a clinical test to detect virus, or by the presence of post- infection antibodies. Responses to vaccination, when the vaccine is available, will also be studied and compared to the responses elicited by active infection. IgG and T-cell responses within the HIV-infected population in response to infection and vaccination will be compared to the responses observed in their HIV- seronegative peers within the MWCCS. The IgG titers and the frequency of SARS-CoV-2 responsive T-cells, their cytokine production, phenotype and durability will be analyzed in a longitudinal fashion until vaccination occurs or we have followed them for two years, whichever comes later. Numbers of senescent T-cells will be determined and associations investigated between the quantify of these cells and the post-infection immune response and severity of disease reported. Pre-SARS-CoV-2 time points will both serve as case controls and allow us to investigate the potential presence of cross-reactive immune responses as two new studies suggest that immune responses to other coronaviruses may be cross-reactive with SARS-CoV-2 which could theoretically impact immune responses to SARS-CoV-2 for better or worse. Our long-term goal is to inform vaccine studies and public policies designed to protect older adults, particularly those aging with HIV.

总结/摘要 几乎没有关于对SARS-CoV-2（COVID 19的病原体）的免疫反应的信息。 我们所知甚少的信息要么是在2020年大流行期间真实的出现的，要么是从一个 关于SARS-CoV-1的一些研究目前最紧迫的问题是， 从SARS-CoV-2感染中恢复的人将具有持久的免疫应答， 再感染和复发性疾病。目前解决这个问题的努力主要集中在抗体上 反应，因为它们不仅比T细胞反应更容易测量，而且抗体提供了第一条线， 适应性免疫保护，并且通常可以在广泛感染发生之前中和病原体。 然而，T细胞在提供针对继发性感染的保护方面也是必不可少的，并且T细胞记忆是 最好是通过疫苗接种。了解T细胞的反应，无论是质量和耐久性，以自然 感染SARS-CoV-2，将不仅提供深入了解SARS-CoV-2的发病机制， 这对疫苗的研制很重要。然而，艾滋病毒感染者，免疫系统缺陷， SARS-CoV-2的发病率和死亡率的高风险人群。因此，理解 这一人群对这种病毒和SARS-CoV-2疫苗的反应。为了调查此事，我们将 描述了IgG以及CD 4+和CD 8 + T细胞亚群在MWCCS参与者中的特征， 确认感染SARS-CoV-2，无论是通过临床试验检测病毒，或通过存在后， 感染抗体当疫苗可用时，还将研究对疫苗接种的反应， 与主动感染引起的反应相比。HIV感染者体内的IgG和T细胞反应 对感染和疫苗接种的反应将与在他们的艾滋病毒中观察到的反应进行比较， MWCCS中的血清阴性同行。IgG滴度和SARS-CoV-2应答性T细胞的频率， 将以纵向方式分析它们的细胞因子产生、表型和耐久性，直到接种疫苗。 或者我们已经跟踪了两年，以较晚者为准。衰老T细胞的数量将是 确定并研究这些细胞的数量与感染后免疫功能之间的关系。 报告的疾病反应和严重程度。SARS前-CoV-2时间点将作为病例对照， 使我们能够研究交叉反应性免疫反应的潜在存在， 对其他冠状病毒的免疫反应可能与SARS-CoV-2交叉反应， 理论上会影响对SARS-CoV-2的免疫反应，无论好坏。我们的长期目标是 疫苗研究和旨在保护老年人的公共政策，特别是那些携带艾滋病毒的老年人。