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年新型冠状病毒研究竞争性修订申请与当前拨款有关