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Temporal variation in HIV-specific IgG subclass Abs during acute infection differentiates spontaneous controllers from chronic progressors.

Temporal variation in HIV-specific IgG subclass Abs during acute infection differentiates spontaneous controllers from chronic progressors.
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Sadanand S, Das J, Chung AW, Schoen MK, Lane S, Suscovich TJ, Streeck H, Smith D, Little S, Lauffenburger DA, Richman D, Alter G,


Sadanand S, Das J, Chung AW, Schoen MK, Lane S, Suscovich TJ, Streeck H, Smith D, Little S, Lauffenburger DA, Richman D, Alter G, (click to view)

Sadanand S, Das J, Chung AW, Schoen MK, Lane S, Suscovich TJ, Streeck H, Smith D, Little S, Lauffenburger DA, Richman D, Alter G,

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AIDS (London, England) 2017 12 12() doi 10.1097/QAD.0000000000001716

Abstract
OBJECTIVE
Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between subjects who ultimately became controllers versus those who became progressors.

METHODS
IgG was purified from plasma from nine acutely infected subjects who subsequently controlled HIV spontaneously (controllers) and ten acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 post-infection. Levels of clade B gp120-, gp140-and gp41-specific IgG antibody subclasses were measured. Additionally, gp120-specific antibody-dependent cellular phagocytosis (ADCP), rapid fluorescent antibody-dependent cellular cytotoxicity (RFADCC), and antibody-dependent cellular viral inhibition (ADCVI) were all assessed.

RESULTS
While no single Ab-related measurement was significantly associated with long-term HIV control, combinations of Ab-associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 Abs and losses in Env-specific IgG3 Abs. Moreover, progressors, but not controllers, lost ADCVI function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection.

CONCLUSIONS
This study suggests that the temporal variation and maintenance of Env-specific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir.

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