一个强大而广泛的CD4结合部位中和抗体,具有强大的ADCC活性,来自中国HIV-1精英中和剂
Yingdan Wang1,2, Ping Ji1, Qianying Liu3
1Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) and Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Cell discovery
|June 9, 2025
概括
一种新的抗体,FD22,对各种HIV-1菌株表现出强大的中和作用,并增强免疫反应. 这一发现为开发针对保护区的新型艾滋病毒疗法和疫苗提供了希望.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 广泛中和抗体 (bNAbs) 针对保存的HIV-1包膜糖蛋白 (Env) 表位是治疗和疫苗开发的关键.
- 精英中和剂提供了强效抗体的来源,为病毒控制机制提供了洞察力.
研究的目的:
- 从长期感染HIV-1的个体中分离和鉴定一种新的CD4结合位点 (CD4bs) 抗体FD22.
- 为了评估FD22.22的中和宽度,效应器功能和表位.
主要方法:
- FD22抗体的分离和表征.
- 伪病毒中和测定对一组多样化的HIV-1菌株进行了分析.
- 功能性检测包括FcγRIIIa参与,NK细胞降粒和抗体依赖细胞细胞毒性 (ADCC).
- 使用AlphaFold3,位点突变和自身病毒逆变异试验进行结构预测.
主要成果:
- 从IGHV3-30衍生出的FD22,具有高体质突变和独特的长CDRH3循环,证明了强大和广泛的中和 (82%的145个伪病毒).
- FD22有效地中和了主要的中国HIV-1菌株 (CRF01_AE,CRF07_BC),并通过FcγRIIIa参与和NK细胞激活诱导了强大的ADCC.
- 皮层映射揭示了FD22的目标是关键的CD4bs区域,其长CDRH3循环通过R102.2独特地相互作用.
结论:
- FD22表现出双重功能,强大的中和和ADCC,使其成为一个有前途的治疗候选者.
- FD22独特的结构特征和广泛的活动为设计下一代CD4bs向HIV疫苗提供了宝贵的见解,这些疫苗具有增强的效应器功能.
相关概念视频
01:40Cell-mediated Immune Responses
Overview
01:20Special Features of Adaptive Immunity
The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
01:26Antigens Involved in Adaptive Immunity
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
01:22T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
01:27Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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01:29Immune Response Against Viral Pathogens
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...