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

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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.

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Acknowledgments

This study was supported by US National Institutes of Health grants R21 AI093294, R21 AI078834, and K22 AI068489 to G. Stone, Grant P30 AI073961 to the Miami Center for AIDS Research (CFAR) at the University of Miami Miller School of Medicine (PI Dr. Savita Pahwa), Florida Biomedical Bankhead-Coley Cancer Research Grant 1BF02 to G. Stone, American Cancer Society Institutional Research Grant 98-277-10, Sylvester Comprehensive Cancer Center (PI Dr. Joseph Rosenblatt) to G. Stone, Stanley J. Glaser Foundation Grant to G. Stone, and the NIH AIDS Reagent Program, Division of AIDS, NIAID.

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  1. Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Sachin Gupta, James M. Termini, Saravana Kanagavelu & Geoffrey W. Stone

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  1. Sachin Gupta
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  2. James M. Termini
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  4. Geoffrey W. Stone
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Gupta, S., Termini, J.M., Kanagavelu, S. et al. Design of vaccine adjuvants incorporating TNF superfamily ligands and TNF superfamily molecular mimics. Immunol Res 57, 303–310 (2013). https://doi.org/10.1007/s12026-013-8443-6

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