Humoral response to viral and self-antigens in HIV infection

HIV感染中对病毒和自身抗原的体液反应

• 批准号: 8664345
• 负责人: John H Elder
• 金额: $ 23.69万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-22 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8664345
• 关键词: Adsorption; Affinity Chromatography; Antibodies; Antibody Formation; Antiviral Response; Antiviral Therapy; Autoantigens; Autoimmune Process; Binding; Biochemical; Biological Assay; Blocking Antibodies; CD4 Antigens; CD8B1 gene; Cells; Complex; Dependence; Development; Disease; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epitopes; Exhibits; Fc Receptor; Feline Immunodeficiency Virus; Felis catus; Gagging; Generations; Grant; HIV; HIV Envelope Protein gp120; HIV Infections; HIV Seropositivity; Homologous Gene; Human; Immune response; Individual; Infection; Intervention; Ligands; Measures; Mutation; Nature; Patients; Relative (related person); Role; Serum; Site; T-Lymphocyte; Vaccines; Viral; Viral Load result; Viral load measurement; Viremia; Virus; Virus Receptors; cohort; improved; in vivo; outcome forecast; public health relevance; receptor; receptor binding; response; screening; success; uptake; vaccine development

DESCRIPTION: The disease prognosis for HIV positive individuals is markedly improved if viral loads are kept at a minimum. Some non-progressors appear to have an innate ability to control virus expression in the absence of antiviral therapies and it is generally assumed that this control of viremia is largely dictated by the humoral and/or cellular immune response to the virus. However, both non-progressors and rapid progressors exhibit substantial immune responses to HIV, with humoral antibody responses particularly directed at the major neutralization target, the viral envelope. Studies of the humoral antibody response associated with FIV infection has revealed the presence of antibodies to the primary binding receptor, CD134, in a high percentage of infected cats. Furthermore, these anti-CD134 antibodies blocked FIV infection ex vivo and their presence correlated with low/slow disease progression in vivo. Reactivity with CD134 occurs at a cryptic epitope that is only exposed when virus binds, thus avoiding potential autoimmune issues. The purpose of the present studies is to pursue characterization of the homologous anti-receptor antibodies against the HIV primary binding receptor, CD4 that we have identified in screening the sera of approximately 300 HIV-infected patients. We wish to determine whether there is a relationship between rate/extent of disease progression and generation of anti-CD4 antibody responses; and 2) whether a subset of anti-CD4 antibodies interfere with HIV infection. To this end, we propose the following Aims: 1). Use Immunoaffinity to purify anti-CD4 antibodies from patient serum and assess the influence of those antibodies on virus uptake into target cells; and 2) Continue screening of additional patient serum to assess anti-CD4,anti-SU, and anti-Gag humoral antibody responses as a function of rate/extent of disease progression, as measured by relative CD4+ and CD8+ T cell levels and viral load. The findings will increase our understanding of the nature of the antiviral response as it relates to protection and thus aid in development of more efficacious vaccine strategies.

描述：如果将病毒负荷保持在最低限度，艾滋病毒阳性个体的疾病预后会明显改善。在没有抗病毒疗法的情况下，一些非培训器似乎具有控制病毒表达的先天能力，通常假定这种病毒血症的控制在很大程度上取决于对病毒的体液和/或细胞免疫反应。然而，非培训器和快速进步者都表现出对艾滋病毒的大量免疫反应，并且尤其针对主要中和靶标病毒包膜的体液抗体反应。与FIV感染相关的体液抗体反应的研究表明，在高百分比感染的猫中，对主要结合受体CD134的抗体存在。此外，这些抗CD134抗体阻断了FIV感染，并且它们的存在与体内的低/缓慢疾病进展相关。与CD134的反应性发生在仅在病毒结合时暴露的神秘表位，从而避免潜在的自身免疫性问题。本研究的目的是追求针对HIV主要结合受体的同源抗受体抗体CD4的表征，我们在筛选大约300例HIV感染患者的血清时已经确定了这些抗体。我们希望确定疾病进展的速率/程度之间是否存在抗CD4抗体反应之间的关系； 2）抗CD4抗体的子集是否会干扰HIV感染。为此，我们提出以下目的：1）。利用免疫亲和力从患者血清中纯化抗CD4抗体，并评估这些抗体对病毒摄取量的影响；和2）继续筛选额外的患者血清，以评估抗CD4，抗SU和抗吸收的体液抗体反应，这是疾病进展率/程度的函数，如相对CD4+和CD8+ T细胞水平以及病毒载量。这些发现将增加我们对抗病毒反应性质的理解，因为它与保护有关，从而有助于开发更有效的疫苗策略。