Immune Dysfunction in HIV + Opiod Users

2019年新型冠状病毒研究的竞争性修订申请与当前的拨款有关 HIV+阿片类药物使用者的免疫功能障碍（DA051202），正在研究 艾滋病毒感染者（PWH）患有阿片类药物使用障碍（OUD）。资助赠款的前提是艾滋病毒 感染损害免疫力，即使在持久的病毒学 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系统。 并证明对PWH特别有害。我们对父母补助金的核心假设是， PWH（HIV + OP+）长期使用阿片类药物会减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+， HIV + OP-和HIV-OP-）作为临床试验接种流感疫苗之前和之后。项目资金 于COVID-19大流行期间开始，导致全球发病率及死亡率上升。的 SARS-CoV-2感染的临床过程是高度可变的，从无症状到严重疾病 导致完全康复、死亡或持续性症状（PASC）（COVID-19急性后遗症后） 19)它可以影响一个或多个器官，如大脑、心脏、肺、肠道、肾脏或肌肉系统 系统由SARs COV-2产生的免疫应答是动态的，涉及先天性和适应性 免疫力，并随着疾病的发展而发展。刺突蛋白受体结合域的抗体 与中和活性相关，是判断现有疫苗有效性的依据， 单克隆抗体治疗。SARS CoV-2感染或接种疫苗后宿主体内抗体的持续时间未知 我们对T细胞在抗体持续存在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发生变化 这取决于宿主的免疫能力，在免疫功能低下的宿主中影响最大。 这些问题与HIV + OP+人群相关，需要进行调查。虽然Ab形成 SARS CoV 2依赖于感染或疫苗接种，SARS CoV 2的T细胞记忆已被证明是 由于常见病毒引起的交叉反应性免疫，在大约50%的一般人群中预先存在 冷冠状病毒。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 体液免疫力下降尽管COVID-19导致运营中断和监管延迟， 项目已经启动，我们认为，在这个时刻进行修订，以纳入与以下方面有关的问题， SARS CoV-2是及时和重要的。在这次修订中，我们建议加入一项综合症试验研究- 在HIV + OP+和其他3种疾病的原始目标背景下，CoV-2血清阳性率和T细胞记忆 研究组（HIV-OP+、HIV + OP-和HIV-OP-）的流感疫苗诱导的免疫应答。

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.