Mark A. Miller, Ph.D.
858 Madison Ave.
801 Molecular Science Building
Memphis, TN 38163
Our research focus is the development of vesicular stomatitis virus (VSV) vector-based vaccine regimens that employ the use of immunomodulatory cytokines as adjuvants. We utilize replication-defective VSV (∆G-VSV), which is capable of only a single round of infection, as a vector for in vivo delivery of cytokine adjuvant in combination with either exogenous or ∆G-VSV-encoded vaccine immunogens. Historically, this work has been performed using the murine model of listeriosis(Listeria monocytogenes),however, due to the dramatic increase in focus on biodefense research our efforts have shifted almost exclusively toward the development of an efficacious vaccine for the category A pathogen, Francisella tularensis (FT).
FT is a gram-negative facultative intracellular bacterium and is the causal agent of the multisyndromic disease that is commonly known as tularemia.Although FT is responsible for only a handful of cases in the U.S. every year (100-200 confirmed cases per year), it is among the most infectious human pathogens known. When acquired via the mucosal route of infection, FT has an LD50 of approximately 10 organisms, and when left untreated carries a mortality rate between 30-60%.This bacterium is relatively easy to aerosolize, and in fact, FT was effectively weaponized by a number of countries (including the U.S.) during the cold war.For these reasons, the CDC and NIH view the development of therapeutic and vaccine protocols for the prevention/treatment of FT infection as high priority goals.
We have received significant support from the NIH to develop novel VSV vector-based cytokine-assisted vaccine protocols for the prophylactic treatment of FT, and we are currently in the 2nd year of a 5-year NIAID contract.The goals of the project are: 1) to identify novel T cell targets of FT, and 2) to develop efficacious single modality and/or mixed-modality vaccine regimens using ∆G-VSV as an in vivo delivery vector. We are also studying the potentially critical role of FT-specific antibodies as effectors of FT immunity, and are hoping to produce monoclonal FT-specific antibodies that can be used effectively for passive immunization of individuals that have been exposed to aerosolized FT.
This project is a truly multidisciplinary effort that directly involves five other members of the Microbiology, Immunology and Biochemistry faculty (Dr. James Bina - bacterial genetics, Dr. Thomas Hatch- Chlamydia pathogenesis, Dr. Tony Marion- immunologist, Dr. Michael Whitt- virologist working on VSV, and Dr. George Hilliard- proteomics/genomics). Because this collection of scientists have very different research interests and experiences, this project offers a terrific opportunity for collaboration and it encourages everyone involved in the project to think outside of their comfort zone with respect to experimental design and understanding of microbial pathogenesis.
- Sheri D. Klas, Clinton D. Robison, Michael A. Whitt, and Mark A. Miller. 2002. Adjuvanticity of VSV-Expressed IL-12 Fusion Protein. Cell. Immunol. 218:59-73.
- Mark A. Miller, Marianne J. Skeen, Christy L. Lavine, and H. Kirk Ziegler. 2003. IL-12-assisted immunization generates CD4+ T cell-mediated immunity to Listeria monocytogenes. Cell. Immunol. 222:1-14.
- Mark A. Miller, Christy L. Lavine, Sheri D. Klas, Lawrence M. Pfeffer, and Michael A. Whitt. 2004. Recombinant replication-restricted VSV as an expression vector for murine cytokines. Protein Express. Purif. 33(1):92-103.
- Sheri D. Klas, Christy L. Lavine, Michael A. Whitt, and Mark A. Miller. 2006. IL-12-assisted immunization against Listeria monocytogenes using replication-restricted VSV-based vectors. Vaccine 24:1451-1461.
- X. Rene Bina, Chunmei Wang, Mark A. Miller, and James E. Bina. 2006. The Bla2 b-lactamase from the live-vaccine strain of Francisella tularensis encodes a functional protein that is only active against penicillin-class b-lactam antibiotics. Arch. Microbiol. (in press).
- Christy L. Lavine. Shawn R. Clinton, Irena Angelova-Fischer Tony N. Marion, James E. Bina, Michael A. Whitt, and Mark A. Miller. 2006. Immunization with heat-killed Francisella tularensis elicits antibody-mediated protective immunity. Infect. Immun. (under review).
- Ph.D, Microbiology, Louisiana State University, 1992
- B.S., Biology and Chemistry, West Texas State University, 1984