EPITOPE MAPPING OF HIV PROTEINS USING ASSAYS IN CONJUCTION W/MASS SEPECTROMETRY
结合质谱分析使用 HIV 蛋白表位作图
基本信息
- 批准号:2452862
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:HIV envelope protein gp120 HIV infections antibody receptor biomarker blood chemistry cancer risk epitope mapping hepatitis human immunodeficiency virus mass spectrometry monoclonal antibody neoplasm /cancer immunodiagnosis neutralizing antibody protein sequence protein structure recombinant virus virus protein
项目摘要
Monoclonal antibodies are routinely used in vitro for diagnosis and in
vivo for diagnosis and immunotherapy. Monoclonal antibodies are used to
screen for cancer biomarkers in high risk patients, HIV or infectious
hepatitis in our nation's blood supply and many other applications.
Knowledge of the epitopes actually being screened for in these diagnostic
kits is vital because sequence variations in the antigens being measured
could lead to false negative results. This is particularly relevant with
the AIDS virus because the virus mutates constantly to avoid recognition
by the host immune system. Thus, the optimal development of in vitro
diagnostic kits which utilize monoclonal antibodies to assay blood for
the presence of HIV necessitates that the epitope being recognized by the
antibody is known and is located in a region of the antigen which
undergoes no sequence variation. If the epitope which is being
recognized by the monoclonal antibody comes from a variable region,
mutations may occur in the protein sequence of the HIV protein and be
missed by the diagnostic kit, leading to tainted blood supplies.
Knowledge of the epitopes enables the development of totally synthetic
vaccines without the need for the inactive pathogen. Synthetic
immunogens have been shown to induce virus neutralizing antibodies. The
advantage of not using a deactivated pathogen for the development of a
vaccine eliminates the possibility of active pathogen contaminating the
vaccine. If the wrong epitope is chosen for preparation of a synthetic
HIV vaccine, deleterious affects can manifest themselves. Not all
antibodies generated by the host immune system are neutralizing. Some
antibodies have been suggested to enhance viral uptake by the Fc
receptor, enhancing infection with HIV. Finally, the use of antibodies
as magic bullets have not yet seen widespread use. Before monoclonal
antibodies can be utilized as pharmacological agents in humans, their
characteristics must be well documented and, of course, this includes a
thorough knowledge of the epitope they recognize. We have identified the
core epitope on recombinant HIVIIIB p26 identified by the monoclonal
antibody 13-102-100 as being residues 102-112. We are currently probing
the epitopes on HIVIIIB p26 recognized by other monoclonal antibodies and
also epitopes of the envelope glycoprotein gp120.
单克隆抗体通常用于体外诊断和免疫治疗。
用于诊断和免疫治疗。 单克隆抗体用于
筛查高危患者、HIV或传染性疾病患者的癌症生物标志物
肝炎在我们国家的血液供应和许多其他应用。
在这些诊断中实际筛选的表位的知识
试剂盒是至关重要的,因为被测抗原的序列变异
可能导致假阴性结果 这一点尤其与
艾滋病病毒,因为病毒不断变异,以避免识别
被宿主免疫系统破坏 因此,体外最佳开发
诊断试剂盒,其利用单克隆抗体来分析血液,
HIV的存在需要抗原决定簇识别的抗原决定簇被抗原决定簇识别。
抗体是已知的并且位于抗原的
没有序列变异。 如果表位被
被单克隆抗体识别的来自可变区,
突变可能发生在HIV蛋白的蛋白序列中,
被诊断试剂盒遗漏导致血液供应被污染
对表位的了解使得能够开发完全合成的
而不需要灭活的病原体。 合成
免疫原已显示出诱导病毒中和抗体。 的
不使用灭活的病原体来开发
疫苗消除了活性病原体污染
疫苗 如果选择了错误的表位来制备合成的
艾滋病毒疫苗,有害影响可以表现出来。 不是所有
由宿主免疫系统产生的抗体是中和性的。 一些
已建议抗体增强Fc对病毒的吸收
受体,增强感染艾滋病毒。 最后,抗体的使用
因为魔术子弹还没有被广泛使用。 单克隆前
抗体可用作人类的药理学试剂,
特性必须有据可查,当然,这包括
对它们所识别的表位的透彻了解。 我们已经确定了
通过单克隆抗体鉴定的重组HIVIIIB p26上的核心表位
抗体13-102-100为残基102-112。 我们目前正在调查
HIVIIIB p26上被其他单克隆抗体识别的表位,
也是包膜糖蛋白GP 120的表位。
项目成果
期刊论文数量(0)
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{{ truncateString('K B TOMER', 18)}}的其他基金
EPITOPE MAPPING OF HIV PROTEINS USING PROTEOLYTIC FOOT PRINTING AND MS
使用蛋白水解足印迹和 MS 对 HIV 蛋白进行表位作图
- 批准号:
6162257 - 财政年份:
- 资助金额:
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热喷雾液质联用技术在生物分子结构解析中的应用
- 批准号:
3918702 - 财政年份:
- 资助金额:
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