The Innate Immunology Laboratory focuses on the role of innate cells in HIV-infection and their contribution to viral control. Invariant Natural Killer T (iNKT) and Mucosal Associated Invariant T (MAIT) cells are innate T cells that recognize structures conserved across pathogens and are restricted by CD1d and MR1 respectively. These cells represent an important first line of defense against pathogens and have the capacity to modulate the adaptive immune response. We aim to understand how HIV impact these cells with the goal of restoring normal levels and functionality of these cells. Another area of interest is to understand how these cells respond to viral vectors and adjuvants used in HIV vaccine with the goal of leveraging their modulatory functions to boost the immune response. Natural killer (NK) cells are considered vital to early protection from diseases and support development of adaptive immune responses. NK cells support immune response through a variety of mechanisms: natural cytotoxicity, antibody dependent cellular cytotoxicity, cytokine/chemokine production and immune modulation through direct cell-to-cell interactions, however, less is known regarding NK cells response to vaccine. We aim to understand how adaptive NK cells may arise following different vaccine regimen and their potential role in preventing infection.
The Fc domain of antibodies can modulate cellular effector functions through interactions with Fc receptors (FcR) on innate immune cells. These interactions can result in activation of Ab-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), complement deposition (ADCD), and pro-inflammatory cytokine production. Following the results of RV144, there is a growing understanding that these antibody effector functions are contributing to prevention of HIV infection. The Innate Immunology Laboratory has developed high throughput assays to measure these functions from clinical trial samples. We are also investigating how adjuvant and innate immune cell sensing can be leveraged to further enhance these functions.