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Polyfunctional HIV-Specific Antibody Responses Are Associated with Spontaneous HIV Control
Margaret E Ackerman1, Anastassia Mikhailova2, Eric P Brown1
1Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
Plos Pathogens
|January 9, 2016
Summary
Elite controllers (ECs) show coordinated antibody functions, not just high antibody levels, for HIV-1 control. This polyfunctional response, involving multiple immune cells, is key for a functional HIV cure.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Elite controllers (ECs) spontaneously control HIV-1 replication.
- Antibodies, particularly antibody-dependent cellular cytotoxicity (ADCC), are implicated in viral containment.
- Understanding antibody effector functions in ECs is crucial for developing functional HIV cures.
Purpose of the Study:
- To define antibody characteristics associated with spontaneous HIV-1 control.
- To investigate the role of extra-neutralizing antibody effector functions in elite controllers.
- To correlate specific antibody subclasses and functions with viral suppression.
Main Methods:
- Profiling of antibody effector functions across HIV-infected individuals with varying viral control.
- Assessment of antibody-dependent cellular cytotoxicity (ADCC), NK cell functions, phagocytosis, and complement.
- Analysis of antibody subclass distribution (IgG1-4) in relation to viral load.
Main Results:
- Elite controllers (ECs) exhibit coordinated, polyfunctional antibody responses, not just increased antibody titers.
- These responses effectively recruit multiple innate immune cells, including NK cells, monocytes, and neutrophils.
- Qualitatively superior IgG3/IgG1 responses were linked to control, while IgG2/IgG4 were associated with poorer antibody activity.
Conclusions:
- Functionally coordinated antibodies, rather than single activities, are critical for HIV-1 control.
- Polyfunctional antibody responses are associated with potent antibody subclasses (IgG3/IgG1).
- Coordinated antibody activity represents a promising strategy for achieving a functional HIV-1 cure.
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