Assistant Clinical Professor
Department of Medicine

Project title: Understanding the mechanism of lentivector-based immunization.

Jerome A. Zack, PhD - UCLA

Multidisciplinary Expertise:
Immunology, Innate immunity, Virology, Signaling Transduction, Vaccines

Project Description:
Dendritic cells (DCs) are critical to stimulating adaptive immune responses owing to their superior ability to process antigens and present them to T cells. Methods have been devised to directly target antigen to DCs for immunization purposes. One effective strategy uses an HIV-1-derived lentiviral vector (LV) to deliver genes encoding antigen to DCs. The in vivo administration of this vector results in the selective expression of antigen in DCs and efficient priming of antigen-specific CD8+ T cells. However, the exact mechanism behind such efficient immunization is not clear. In this project we seek to understand how LVs perform two independent functions: delivery of antigen and activation of DCs. We expect to identify the mechanisms of LV antigen delivery, the immunostimulatory LV components and corresponding host innate immune signaling pathways. In addition, our findings will raise important questions regarding the nature of particles in vector preparations and discovery of novel immune agonists for vaccination.