Grant: Project Grant

Increasing evidence suggests that the first immune responses, also termed innate immunity, are key determinants of the outcome of HIV infection. Modulation of innate immunity, thus has the potential to constitute a powerful effector strategy to complement traditional approaches to HIV prevention and therapy. However, a better understanding of the contribution of specific components of the host innate response to early HIV control is a critical prerequisite for the use of innate immunity in vaccine or therapy design. This project focuses on plasmacytoid Dendritic Cells (pDCs), a critical cellular component of our innate immune system that is activated early on during HIV infection and that is thought to mediate potent antiviral activities. These immune cells are quantitatively and functionally affected in HIV infection. CDX-301 is a form of a factor naturally produced by humans, which induces an expansion of immune cell precursors as well as pDCs. CDX-301 is currently in clinical development for cancer immunotherapy and as a vaccine adjuvant. In this project, we will study the role of pDCs during early HIV infection by testing whether their expansion by CDX-301 can mediate potent immune responses that could contribute to HIV control. Towards this goal, we will use mouse that are transplanted with a human immune system. These so called humanized (hu) mice are susceptible to HIV infection and recapitulate most of the characteristics of HIV-induced disease. Specifically, we will analyze the effect of CDX-301-mediated pDC expansion on HIV infection, spread and development of disease in hu mice. Furthermore, we will characterize the immune effectors induced by CDX-301-mediated pDC expansion and their effects on HIV infection. Ultimately, understanding how CDX-301 and pDCs can mediate control of HIV infection following virus transmission will offer unique opportunities for the development of improved or novel preventive and therapeutic strategies against HIV infection