High-resolution definition of humoral immune response correlates of effective immunity against HIV.

High-resolution definition of humoral immune response correlates of effective immunity against HIV.
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DOI:
10.15252/msb.20177881
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发表时间:
2018-03-26
影响因子:
9.9
通讯作者:
Ackerman ME
Ackerman ME
中科院分区:
生物学1区
文献类型:
--
作者:
Alter G;Dowell KG;Brown EP;Suscovich TJ;Mikhailova A;Mahan AE;Walker BD;Nimmerjahn F;Bailey-Kellogg C;Ackerman ME

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通过全面询问自然或实验保护对象中广泛的生物多样性来确定免疫相关因素,可能为指导有效疫苗和基于抗体的疗法的开发提供至关重要的见解。我们报告了体液免疫分析方法的进展及其在阐明有效的HIV - 1病毒控制标志方面的应用。采用高分辨率、高通量的生物物理抗体分析方法,对具有不同病毒控制的HIV感染者进行了系统的血清学分析,提供了对体液反应的无偏解剖,以及功能抗体分析,表征了抗体导向的效应功能,如补体固定和吞噬作用,这是保护性免疫的核心。研究人员对不同病毒控制的受试者进行了计算分析和建模,以便解绕IgG Fab特性、Fc特性和效应物功能之间的关系,并确定有效的抗病毒抗体导向效应物活性和有效的病毒抑制的体液相关性。由此产生的模型揭示了多克隆抗体对多种抗病毒反应的多方面和协调的贡献,并提出了预测病毒控制的关键生物物理特征。
Defining correlates of immunity by comprehensively interrogating the extensive biological diversity in naturally or experimentally protected subjects may provide insights critical for guiding the development of effective vaccines and antibody‐based therapies. We report advances in a humoral immunoprofiling approach and its application to elucidate hallmarks of effective HIV‐1 viral control. Systematic serological analysis for a cohort of HIV‐infected subjects with varying viral control was conducted using both a high‐resolution, high‐throughput biophysical antibody profiling approach, providing unbiased dissection of the humoral response, along with functional antibody assays, characterizing antibody‐directed effector functions such as complement fixation and phagocytosis that are central to protective immunity. Profiles of subjects with varying viral control were computationally analyzed and modeled in order to deconvolute relationships among IgG Fab properties, Fc characteristics, and effector functions and to identify humoral correlates of potent antiviral antibody‐directed effector activity and effective viral suppression. The resulting models reveal multifaceted and coordinated contributions of polyclonal antibodies to diverse antiviral responses, and suggest key biophysical features predictive of viral control.
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