Grant: Project Grant

Antibody (Ab) molecules have an Fab region, which binds antigen specifically and an Fc region, which binds to various Fc receptors (FcR) on many types of innate immune cells. Fc-FcR interactions can activate FcR+ innate immune cells and induce anti-viral activity. Which FcR an Ab Fc region binds and the strength of the binding interaction depends on the Ab immunoglobulin class, the amino acid sequence of the Fc domain and the composition of added sugars (i.e. Fc biophysical features). These Fc features in turn determine which innate immune cells are activated for functions that can kill or clear pathogens (i.e. function). The pattern of HIV-specific Ab Fc functions and features differs in recipients of protective versus non protective HIV vaccines. Remarkably, the rare subset of HIV infected individuals, known as Elite Controllers (ECs) have patterns of Fc functions and features that differ from those seen in progressors suggesting that Ab dependent anti-HIV activity can control HIV. The proposal will investigate this hypothesis by considering the degree of HIV control as measured by HIV viral load (VL) and cellular HIV reservoir size and how these correlate with Fc dependent parameters. HIV+ ECs and those starting treatment in acute infection (AT) can achieve similarly low HIV viral loads and HIV reservoirs unlike those left untreated or who start treatment late in infection. But AT loose HIV control when treatment is stopped. We will investigate whether and which patterns of HIV-specific Ab Fc parameters distinguish EC from AT. The goal will be to better understand the link between Ab dependent activity and HIV control. The field of Ab therapeutics is developing ways to deliver and engineer Abs having desirable characteristics for particular disease outcomes. The information learned from this project will characterize the Ab Fc parameters that support HIV control thus potentially providing a benchmark for therapeutic Ab design for control of HIV infection.