Design of vaccine adjuvants incorporating TNF superfamily ligands and TNF superfamily molecular mimics.

TNF superfamily ligands play a critical role in the regulation of adaptive immune responses, including the costimulation of dendritic cells, T cells, and B cells. This costimulation could potentially be exploited for the development of prophylactic vaccines and immunotherapy. Despite this, there have been only a limited number of reports on the use of this family of molecules as gene-based adjuvants to enhance DNA and/or viral vector vaccines. In addition, the molecule latent membrane protein 1 (LMP1), a viral mimic of the TNF superfamily receptor CD40, provides an alternative approach for the design of novel molecular adjuvants. Here, we discuss advances in the development of recombinant TNF superfamily ligands as adjuvants for HIV vaccines and as cancer immunotherapy, including the use of LMP1 and LMP1-CD40 chimeric fusion proteins to mimic constitutive CD40 signaling.