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

被引：35

作者：

Alter, Galit ^{[1
]}

Dowell, Karen G. ^{[2
]}

Brown, Eric P. ^{[3
]}

Suscovich, Todd J. ^{[1
]}

Mikhailova, Anastassia ^{[1
]}

Mahan, Alison E. ^{[1
]}

Walker, Bruce D. ^{[1
]}

Nimmerjahn, Falk ^{[4
]}

Bailey-Kellogg, Chris ^{[2
]}

Ackerman, Margaret E. ^{[3
]}

机构：

[1] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA

[2] Dartmouth Coll, Dept Comp Sci, Hanover, NH 03755 USA

[3] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA

[4] Univ Erlangen Nurnberg, Inst Genet, Dept Biol, Erlangen, Germany

来源：

MOLECULAR SYSTEMS BIOLOGY | 2018年 / 14卷 / 03期

基金：

美国国家卫生研究院;

关键词：

antibody; effector function; HIV; systems serology; ANTIGEN-SPECIFIC ANTIBODIES; CELL-MEDIATED CYTOTOXICITY; GENERALIZED LINEAR-MODELS; YELLOW-FEVER VACCINE; SYSTEMS BIOLOGY; HIGH-THROUGHPUT; PROTECTIVE EFFICACY; PHAGOCYTIC-ACTIVITY; RHESUS-MONKEYS; IGG FC;

D O I：

10.15252/msb.20177881

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：14

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