Robert E. Johnston, Ph.D.

rjohnst@med.unc.edu 9004 Burnett-Womack Campus Box 7292 Chapel Hill, NC 27599-7292 919.966.3507

Research

Our research is in two areas, the molecular genetics of viral pathogenesis and its application to vaccine design. The first area is an investigation of the pathogenesis of Venezuelan equine encephalitis virus (VEE). In the mouse model of VEE infection, we are examining the lymphotropic and neurotropic aspects of the disease, the initial cells targeted after inoculation, the role of viremia in invasion of the central nervous system (CNS), immune mechanisms of clearance from the CNS, and the genetics of pathogenesis. In the latter studies, we have used, as an intellectual scaffolding, the paradigm of biochemical genetics, that failure to synthesize the end product of a biochemical pathway indicates a genetic lesion in one of the enzymes of that pathway. By analogy, we have viewed viral pathogenesis as a succession of steps leading to death. Virus mutants which fail to cause death must, of necessity, be deficient in one or more steps in the pathogenesis “pathway.” We have used a series of site-directed mutants in the molecularly cloned virus background to elucidate several of the steps in VEE pathogenesis and to examine the genetics of reversion to virulence in vivo. This work is supported by an NIH R01 grant, currently funded through its 16th year (2005).



The second area is design of live virus vaccines and vaccine vectors. In animal models of several important human and animal pathogens, e.g. influenza, Marburg, Ebola and simian immunodeficiency virus, VEE vectored vaccines have proven safe, immunogenic and protective. This work was initiated with a grant from the Henry M. Jackson Foundation in 1994, and our group, in conjunction with AlphaVax, Inc., was chosen, in 1998, as one of the two initial AIDS Vaccine Design Teams by the International AIDS Vaccine Initiative (IAVI). Under the auspices of IAVI, NIH, and the South African AIDS Vaccine Initiative, phase I clinical trials have begun at four sites in the U.S. with two sites in South Africa to begin in 2003. In 1999, we were designated as one of the NIH HIV Vaccine Research and Design teams, and under this funding (through 2004), we are designing and testing second-generation VEE-vectored prophylactic HIV vaccines. An additional grant from NIH (through 2006) is supporting the design, manufacture and clinical testing of a therapeutic HIV vaccine concept.

Publications

Schäfer A, Brooke CB, Whitmore AC, Johnston RE (2011). The role of the blood brain barrier during Venezuelan equine encephalitis virus infection. J Virol.

Brooke CB, Deming DJ, Whitmore AC, White LJ, Johnston RE (2010). T cells facilitate recovery from Venezuelan equine encephalitis virus-induced encephalomyelitis in the absence of antibody.
J Virol. 84(9):4556-68.

Konopka JL, Thompson JM, Whitmore AC, Webb DL, Johnston RE (2009). Acute infection with venezuelan equine encephalitis virus replicon particles catalyzes a systemic antiviral state and protects from lethal virus challenge. J Virol. 83(23):12432-42.

Schäfer A, Whitmore AC, Konopka JL, Johnston RE (2009). Replicon particles of Venezuelan equine encephalitis virus as a reductionist murine model for encephalitis. J Virol. 83(9):4275-86.

Thompson JM, Whitmore AC, Staats HF, Johnston RE (2008). Alphavirus replicon particles acting as adjuvants promote CD8+ T cell responses to co-delivered antigen. Vaccine. 26(33):4267-75.

Thompson JM, Nicholson MG, Whitmore AC, Zamora M, West A, Iwasaki A, Staats HF, Johnston RE (2008). Nonmucosal alphavirus vaccination stimulates a mucosal inductive environment in the peripheral draining lymph node. J Immunol. 181(1):574-85.

Konopka JL, Penalva LO, Thompson JM, White LJ, Beard CW, Keene JD, Johnston RE (2007). A two-phase innate host response to alphavirus infection identified by mRNP-tagging in vivo. PLoS Pathog. 3(12):e199.

Montgomery SA, Johnston RE (2007). Nuclear import and export of Venezuelan equine encephalitis virus nonstructural protein 2. J Virol. 81(19):10268-79.

White LJ, Parsons MM, Whitmore AC, Williams BM, de Silva A, Johnston RE (2007). An immunogenic and protective alphavirus replicon particle-based dengue vaccine overcomes maternal antibody interference in weanling mice. J Virol. 81(19):10329-39.

Thornburg NJ, Ray CA, Collier ML, Liao HX, Pickup DJ, Johnston RE (2007). Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge. Virology. 362(2):441-52.

Thompson JM, Whitmore AC, Konopka JL, Collier ML, Richmond EM, Davis NL, Staats HF, Johnston RE (2006). Mucosal and systemic adjuvant activity of alphavirus replicon particles. Proc Natl Acad Sci U S A. 103(10):3722-7.

Thomas CE, Zhu W, Van Dam CN, Davis NL, Johnston RE, Sparling PF (2006). Vaccination of mice with gonococcal TbpB expressed in vivo from Venezuelan equine encephalitis viral replicon particles. Infect Immun. 74(3):1612-20.

Johnston RE, Johnson PR, Connell MJ, Montefiori DC, West A, Collier ML, Cecil C, Swanstrom R, Frelinger JA, Davis NL (2005). Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660. Vaccine. 23(42):4969-79.

Click here for a list of publications

Affiliations

Carolina Vaccine Institute
Department of Microbiology & Immunology
Center for HIV/STDs and Infectious Disease (CFID)
Lineberger Comprehensive Cancer Center (LCCC)