Harnessing Human Dendritic Cell Subsets for Improved Vaccines

Abstract

Dendritic cells (DCs) orchestrate a repertoire of immune responses that endow resistance to infection and tolerance to self. DC plasticity and subsets are prominent determinants of the quality of elicited immune responses. For example, CD14+ dermal DCs preferentially control humoral immunity, inducing B-cell priming and differentiation of follicular helper T cells. By contrast, epidermal DCs, known as Langerhans’ cells (LCs), preferentially induce cellular immunity through their ability to prime CD8+ cytotoxic T cells. Several clinical trials testing ex vivo-generated DC vaccines charged with melanoma antigens, carried out at the Baylor Institute for Immunology Research (TX, USA), have resulted in immune and clinical responses in patients. Another approach to the development of vaccines that we are pursuing involves in vivo targeting of DCs with anti-DC antibody fusion proteins that carry a series of antigens, including influenza, HIV and cancer antigens on their fragment crystallizable (Fc) region. We foresee that targeting LCs will be important for the design of vaccines that aim at eliciting strong cellular immunity. Such vaccines might be particularly useful at preventing, and perhaps even treating, chronic diseases, including viral (HIV or hepatitis C virus), bacterial (mycobacteria) and parasitic (malaria) diseases, as well as cancer. The most efficient vaccines might actually be those that will target both CD14+ DCs and LCs, thereby allowing the maximal stimulation of both humoral and cellular immune responses.