Open AccessHigh‐resolution definition of humoral immune response correlates of effective immunity against HIV
Author(s) -
Alter Galit,
Dowell Karen G,
Brown Eric P,
Suscovich Todd J,
Mikhailova Anastassia,
Mahan Alison E,
Walker Bruce D,
Nimmerjahn Falk,
BaileyKellogg Chris,
Ackerman Margaret E
Publication year - 2018
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20177881
Subject(s) - library science , human immunodeficiency virus (hiv) , history , biology , computer science , immunology
Abstract 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.