title: Design of vaccine adjuvants incorporating TNF superfamily ligands and TNF superfamily molecular mimics.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Gupta
authors.forename: James M
authors.initials: JM
authors.lastname: Termini
authors.forename: Saravana
authors.initials: S
authors.lastname: Kanagavelu
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000737:chemistry / Q000378:metabolism; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D016086:Lentivirus / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008253:Macaca mulatta; D018716:Molecular Mimicry / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D055503:Protein Multimerization; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry; D051193:Toll-Like Receptors / Q000819:agonists; D048069:Tumor Necrosis Factors / Q000737:chemistry; D014612:Vaccines / Q000737:chemistry* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D019496:Cancer Vaccines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008024:Ligands; D053221:TNF-Related Apoptosis-Inducing Ligand; D051193:Toll-Like Receptors; D048069:Tumor Necrosis Factors; D014612:Vaccines; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; D023201:CD40 Ligand