Immune Dysfunction in HIV + Opiod Users

HIV阿片使用者的免疫功能障碍

基本信息

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
项目类别：
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

项目摘要

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.

本次2019年新型冠状病毒研究竞争性修订申请与当前资助相关 HIV+阿片类药物使用者的免疫功能障碍 (DA051202) 正在调查流感疫苗的反应患有阿片类药物使用障碍 (OUD) 的艾滋病毒感染者 (PWH)。资助的前提是艾滋病毒感染会损害免疫力，有证据表明，即使经过持久的病毒学检查，免疫扰动仍持续存在控制。阿片类药物具有免疫抑制作用，通过处方或注射滥用可能会损害免疫功能。免疫系统，并被证明对感染者特别有害。我们在家长资助中的中心假设是艾滋病毒感染者 (HIV+OP+) 长期使用阿片类药物会削弱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 组参与者（HIV+OP+、HIV-OP+、作为临床试验，注射流感疫苗之前和之后 HIV+OP- 和 HIV-OP-）。项目资金这场疫情始于新冠肺炎 (COVID-19) 大流行期间，导致全球发病率和死亡率上升。这 SARS-CoV-2 感染的临床病程变化很大，从无症状到严重疾病导致完全康复、死亡或持续出现 PASC 症状（新冠肺炎急性后遗症） 19) 可影响一种或多种器官，如大脑、心脏、肺、肠道、肾脏或肌肉骨骼系统。 SAR COV-2 产生的免疫反应是动态的，涉及先天性和适应性免疫力并随着疾病的阶段而发展。刺突蛋白受体结合域的抗体与中和活性相关并构成判断当前疫苗有效性的基础以及单克隆抗体治疗。 SARS CoV-2 感染或接种疫苗后，抗体在宿主体内的持续时间未知我们对 T 细胞在抗体持久性或病毒出现中的作用的认识存在空白变体。目前还不清楚 COVID-19 是否会对免疫力造成有害影响以及这种影响是否会有所不同取决于宿主的免疫能力，对免疫功能低下的宿主影响最大。这些问题与 HIV+OP+ 人群相关，需要进行调查。当抗体形成时 SARS CoV 2 依赖于感染或疫苗接种，T 细胞对 SARS CoV2 的记忆已被证明由于常见菌引起的交叉反应免疫，大约 50% 的普通人群中已存在冷电晕病毒。这种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，或减轻疾病的严重程度，特别是在缺乏或缺乏的情况下体液免疫力下降。尽管由于 COVID-19 造成运营中断和监管延误，我们的项目已经启动，我们认为此时进行修订以纳入以下相关问题 SARS CoV-2 的出现是及时且重要的。在本次修订中，我们建议纳入一项针对 SARS 的试点研究 HIV+OP+ 和其他 3 个原始目标背景下的 CoV-2 血清流行率和 T 细胞记忆正在研究流感疫苗诱导的免疫反应的群体（HIV-OP+、HIV+OP-和HIV-OP-）。