Immune Dysfunction in HIV + Opiod Users

HIV阿片使用者的免疫功能障碍

• 批准号: 10552153
• 负责人: Savita Pahwa
• 金额: $ 15.35万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10552153
• 关键词: AIDS/HIV problem; Address; Adult; Affinity; Analgesics; Antibodies; Antibody Formation; Antibody Response; Antigens; Area; B-Lymphocytes; Blood specimen; Brain; CD4 Positive T Lymphocytes; Cell Count; Cell Maturation; Cells; Cessation of life; Characteristics; Chronic; Cities; Clinic; Coupled; Dangerousness; Data; Data Set; Defect; Dependence; Development; Epidemic; Evaluation; Exhibits; Failure; Feasibility Studies; Flow Cytometry; Frequencies; Functional disorder; Future; Generations; Genetic Transcription; Genomic approach; HIV; HIV Infections; HIV Seronegativity; Helper-Inducer T-Lymphocyte; Human; Immune; Immune System Diseases; Immune response; Immune system; Immunity; Immunocompetence; Immunoglobulin Somatic Hypermutation; Immunologics; Impairment; In Vitro; Incidence; Inflammation; Inflammatory; Influenza; Influenza A Virus, H1N1 Subtype; Influenza vaccination; Interleukin-2; Intervention; Lead; Lymphoid; Memory; Memory B-Lymphocyte; Morphine; Nucleic Acids; Opiate Addiction; Opioid; Opioid Receptor; Participant; Patients; Peripheral; Personal Satisfaction; Persons; Phenotype; Plasma; Plasmablast; Play; Population; Property; Receptor Signaling; Recovery; Research; Resolution; Seasons; Serology; Signal Transduction; Structure of germinal center of lymph node; Subgroup; Surface; T-Lymphocyte Subsets; Technology; Testing; Universities; Vaccination; Vaccine Antigen; Vaccinee; Vaccines; Viral; addiction; antagonist; base; delta opioid receptor; drug abuser; flu; functional disability; genomic platform; immune activation; immune function; indexing; inflammatory marker; influenza infection; influenza virus vaccine; insight; interest; neglect; novel; opioid epidemic; opioid injection; opioid use; opioid user; peripheral blood; prescription opioid; prevent; programs; receptor; recruit; responders and non-responders; response; seasonal influenza; single cell technology; therapeutic vaccine; tool; transcriptomics; trivalent influenza vaccine; vaccine response; vaccine-induced antibodies

This Competitive Revision application for 2019 Novel Coronavirus research is related to the current grant Immune Dysfunction in HIV+ Opioid Users (DA051202) which is investigating influenza vaccine responses in people with HIV (PWH) who have opioid use disorder (OUD). The premise for the funded grant is that HIV infection impairs immunity with evidence of persisting immune perturbations even after durable virologic control. Opioids are immunosuppressive and abuse through prescription or injection can be damaging to the immune system and prove to be specially harmful in PWH. Our central hypothesis in the parent grant is that chronic opioid use by PWH (HIV+OP+) blunts the immune response and impairs the generation of influenza vaccine induced immune response. Our plan is to investigate participants in 4 groups (HIV+OP+, HIV-OP+, HIV+OP- and HIV-OP-) before and after influenza vaccine administered as a clinical trial. The project funding started in the midst of the COVID-19 pandemic that has resulted in global morbidity and mortality. The clinical course of SARS-CoV-2 infection is highly variable, ranging from asymptomatic to severe disease resulting in full recovery, death, or persistent symptoms described as PASC (post acute sequalae of COVID- 19) which can affect one or more organs such as the brain, heart, lung, gut, kidneys, or musculosleletal system. The immune response generated by SARs COV-2 is dynamic, involves innate and adaptive immunity and evolves with the stage of the disease. Antibodies to the spike protein's receptor binding domain corelate with neutralizing activity and form the basis of judging effectiveness of current vaccines as well as monoclonal Ab therapy. Duration of Ab in the host following SARS CoV-2 infection or vaccination is unknown and there are gaps in our knowledge about the role of T cells in Ab persistence or emergence of viral variants. It is also unknown if COVID-19 causes detrimental effects on immunity and if this effect varies depending on the host's immune competence, with the greatest impact in an immunocompromised host. These issues are relevant for the HIV+OP+ population and need to be investigated. While Ab formation to SARS CoV 2 is dependent upon infection or vaccination, T cell memory for SARS CoV2 has been shown to pre-exist in approximately 50% of the general population due to cross reactive immunity induced by Common Cold Corona viruses. Such SARS-CoV-2 specific memory T cells are considered to be beneficial to the host, affording protection from infection, or reduction in disease severity, particularly in the face of absent or waning humoral immunity. Despite the disruption in operations and regulatory delays due to COVID-19 our project has been initiated, and we feel that a revision at this juncture to incorporate questions related to SARS CoV-2 are timely and important. In this revision we are proposing to incorporate a pilot study of SARS- CoV-2 seroprevalence and T cell memory in the context of original aims in the HIV+OP+ and the other 3 groups (HIV-OP+, HIV+OP- and HIV-OP-) being investigated for flu vaccine induced immune responses.

2019年新颖冠状病毒研究的竞争性修订申请与当前的赠款有关 HIV+阿片类药物使用者（DA051202）的免疫功能障碍，正在研究流感疫苗反应 患有阿片类药物使用障碍（OUD）的艾滋病毒（PWH）的人。资助赠款的前提是艾滋病毒 感染会损害免疫力，即使在持久的病毒学之后，也具有持续的免疫扰动的证据 控制。阿片类药物是免疫抑制的，通过处方或注射滥用可能会损害 免疫系统，被证明在PWH中特别有害。我们在父母赠款中的中心假设是 PWH（HIV+OP+）的慢性阿片类药物使用会钝化免疫反应并损害流感的产生 疫苗诱导的免疫反应。我们的计划是调查4组的参与者（HIV+OP+，HIV-OP+， 在流感疫苗作为临床试验中给药之前和之后，HIV+OP-和HIV-OP-）。项目资金 始于导致全球发病率和死亡率的Covid-19-19大流行。这 SARS-COV-2感染的临床过程高度可变，范围从无症状到严重疾病 导致完全康复，死亡或持续性症状被描述为PASC 19）会影响一个或多个器官，例如大脑，心脏，肺，肠道，肾脏或肌肉骨骼骨骼 系统。 SARS COV-2产生的免疫反应是动态的，涉及先天和适应性 免疫力并随着疾病的阶段而发展。尖峰蛋白受体结合结构域的抗体 与中和活性相结合，构成了当前疫苗的有效性以及 单克隆AB疗法。 SARS COV-2感染或疫苗接种后，主机中AB的持续时间未知 我们关于T细胞在AB持久性或病毒出现中的作用的知识存在差距 变体。同样未知Covid-19是否对免疫产生不利影响，并且这种影响是否有所不同 取决于宿主的免疫能力，对免疫功能低下的宿主产生最大的影响。 这些问题与HIV+ OP+人群有关，需要研究。而ab的形成 SARS COV 2取决于感染或疫苗接种，SARS COV2的T细胞记忆已显示为 由于共同引起的交叉反应性免疫，大约50％的普通人群中存在预先存在 冷的电晕病毒。这样的SARS-COV-2特异性记忆T细胞被认为对宿主有益， 提供免受感染的保护或疾病严重程度的减轻，特别是面对缺席或 逐渐减弱的体液免疫。尽管行动和监管延迟造成了造成的破坏，因此我们 已经启动了项目，我们认为该关头进行了修订，以结合与之相关的问题 SARS COV-2是及时且重要的。在这项修订中，我们建议将SARS的试点研究纳入 在HIV+ OP+和其他3中，COV-2的血清阳性和T细胞存储器在原始目标的背景下 研究了流感疫苗诱导的免疫反应的组（HIV-OP+，HIV+OP-和HIV-OP-）。