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)正在调查流感疫苗的反应 艾滋病毒携带者(PWH)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，有证据表明即使在持久的病毒学之后仍存在免疫紊乱 控制力。阿片类药物具有免疫抑制作用，通过处方或注射滥用可损害 免疫系统，并被证明是特别有害的PWH。我们在父母资助中的中心假设是 PWH(HIV+OP+)长期使用阿片类药物会削弱免疫反应，损害流感的产生 疫苗可诱导免疫应答。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。项目资金 始于新冠肺炎大流行，已导致全球发病率和死亡率。这个 SARS-CoV-2感染的临床病程变化很大，从无症状到严重疾病不等。 导致完全康复、死亡或持续的症状，描述为PASC(COVID的急性后遗症- 19)会影响一个或多个器官，如大脑、心脏、肺、肠道、肾脏或肌肉骨骼 系统。SARS COV-2产生的免疫反应是动态的，涉及先天和获得性 免疫力，并随着疾病的发展而演变。抗S蛋白受体结合域的抗体 与中和活性相关，构成判断当前疫苗有效性的基础，以及 单抗治疗。SARS CoV-2感染或接种后抗体在宿主中的持续时间未知 关于T细胞在抗体持续存在或病毒出现中的作用，我们的知识存在空白 变种。新冠肺炎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，目前还不清楚 取决于宿主的免疫能力，在免疫受损的宿主中影响最大。 这些问题与艾滋病毒+OP+人群有关，需要进行调查。而抗体形成到 SARS CoV2依赖于感染或疫苗接种，已表明SARS CoV2的T细胞记忆 大约50%的普通人群中预先存在，这是由于共同免疫诱导的交叉反应免疫 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， 提供免受感染或减轻疾病严重程度的，尤指在缺乏或 体液免疫力减弱。尽管新冠肺炎导致运营中断和监管延误，但我们的 项目已经启动，我们认为在这个节骨眼上进行修订，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，我们建议纳入一项关于SARS的初步研究- HIV+OP+和其他3例患者原始目标背景下的CoV-2血清阳性率和T细胞记忆 正在研究流感疫苗诱导免疫反应的群体(HIV-OP+、HIV+OP-和HIV-OP-)。

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.