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Dr. Halford

            Pub Med

William Halford
Associate Professor
phone: 217.545.4277
halford@siumed.edu

Research Interests

   There are 126 known herpesviruses that infect animals and eight herpesviruses that infect humans.  Work in the Halford Lab focuses on two of these viruses: 

  • herpes simplex virus 1 (HSV-1), which causes recurrent cold sores (oral herpes)
  • herpes simplex virus 2 (HSV-2), which causes recurrent genital herpes.

  Despite the tendency of these two viruses to infect different sites in the body, HSV-1 and HSV-2 are 99% genetically identical.  About 175 million Americans are latently infected with HSV-1, and ~55 million are latently infected with HSV-2.  Although only 5% of infected people experience frequent, recurrent outbreaks, this translates into roughly 10 million Americans who get recurrent cold sores and 3 million who experience 1 to 4 outbreaks of genital herpes each year.

Research Goals:

   From a basic science viewpoint, Dr. Halford's research focuses on elucidating how key factors such as HSV's ICP0 protein and the host interferon response contribute to HSV's ability to "choose" between productive replication and non-productive infection each time the virus enters a new cell in vivo.  For more information on this topic, see Chapter 5 of Viruses and Interferon: Current Research, 2011.

   From the clinical viewpoint, the basic science described above suggests a simple and rational path that would yield a new class of HSV-2 vaccine.  Specifically, interferon-sensitive HSV-2 ICP0- mutant viruses should be unable to cause disease in experimental animals or humans, but effectively prime the adaptive immune system such that the vaccine recipient is resistant to later exposures to wild-type HSV-2.  Published work and ongoing experiments in the lab indicate that, in fact, live HSV-2 ICP0- mutant viruses are a viable strategy to obtain a safe and effective HSV-2 vaccine that renders vaccinated animals completely resistant to HSV-2 genital herpes.  Work in the laboratory is currently focused on determining how effective these live HSV-2 vaccine strains are relative to three HSV-2 vaccine candidates that have previously advanced to human clinical trials; namely, 1. protein subunit vaccines such as Glaxo Smith Kline's Herpevac vaccine, 2. replication-defective HSV-2 viruses such as Sanofi Pasteur's ACAM-529 vaccine, and 3. live-attenuated HSV-2 viruses bearing mutations in 4 or more viral genes (Biovex's ImmunovexHSV-2 vaccine).

   Updates on the status of research and development of Dr. Halford's live HSV-2 vaccine candidates may be found at http://herpesvaccineresearch.com/.

Education:

  • Ph.D. Louisiana State University Medical School, 1996, Viral immunology
  • M.S. Louisiana State University Medical School, 1994, Immunology
  • B.S. University of California at Santa Barbara, 1991, Marine Biology

Professional Experience

  • 2007- Associate Professor, Medical Microbiology, Immunology & Cell Biology, Southern Illinios University School of Medicine
  • 2004-2007 Assistant Professor, Veterinary Molecular Biology, Montana State University
  • 2004-2007 Affiliate Assistant Professor, Microbiology, University of Washington
  • 2000-2004 Assistant Professor, Microbiology and Immunology, Tulane University

Funding

  • 2012 - 2013 Prophylactic and Therapeutic Vaccines for Ocular HSV-1, Louisiana Vaccine Center. $75,000. P.I. Hill.  Dr. Halford is a Co-Investigator on this grant in name, but received  $0 for his role in getting the grant funded
  • 2009 - 2012 Development of an effective genital herpes vaccine.  R21 AI81072, National Institutes of Health
  • 2011 A safe and effective genital herpes vaccine. Excellence in Academic Medicine Grant, Southern Illinois University
  • 2010 - present: Herpes Vaccine Fund, supported by donations from private citizens for the purpose of bringing a safe and effective HSV-2 vaccine to human clinical trials.  Please consider donating, as explained at the following link: http://herpesvaccineresearch.com/.

Patents

  • Davido, D. and W.P. Halford. 2010. Herpes simplex virus mutant ICP0.  U.S. Patent 20100226940.

Selected Publications

  • Halford, W.P., J. Geltz, and E. Gershburg.  2013.  Pan-HSV-2 IgG antibody in vaccinated mice and guinea pigs correlates with protection against herpes simplex virus 2.  PLoS ONE:  In revision.
  • Nixon, B., M. Stefanidou, P. Mesquita, E. Fakioglu, T. Segarra, L. Rohan, W. Halford, K. Palmer, and B. Herold. 2013.  Griffithsin Protects Mice from Genital Herpes by Preventing Cell-to-Cell Spread.  J Virol  In press.
  • Hill, J.M., M. Nicole, H.E. McFerrin, C. Clement, T.P. Foster, W.P. Halford, G.K. Kousoulas, W.G. Lukiw, J. Walter, H.W.  Thompson, E.M. Stern, and P.S. Bhattacharjee.  2012.  HSV-1 latent rabbits shed viral DNA into their saliva.  Virol. J. 9:221.
  • Halford, W.P., R. Püschel, E. Gershburg, A. Wilber, S. Gershburg, and B. Rakowski.  2011. A live-attenuated HSV-2 ICP0- virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine.  PLoS ONE 6 (3): e17748. (Abstract)
  • Halford, W. P., and B. M. Gebhardt. 2011.  Host interferon: a silent partner in the regulation of herpes simplex virus latency.  Chapter 5 in K. L. Mossman (ed.), Viruses and Interferon: current research. Publication date:  May 2011. Book website: http://www.horizonpress.com/viruses-interferon
  • Conrady, C.D., W.P. Halford, and D.J.J. Carr.  2011.  The loss of the type I interferon pathway increases vulnerability of mice to genital HSV-2 infection.  J. Virol. 85: 1625 - 1633. (Abstract)
  • Halford, W.P., R. Püschel, and B. Rakowski. 2010.  Herpes simplex virus 2 ICP0 - mutants are avirulent and immunogenic: implications for a genital herpes vaccine. PLoS ONE 5(8): e12251. (Abstract)
  • Liu, M., E.E. Schmidt, and W.P. Halford.  2010.  ICP0 dismantles microtubule networks in herpes simplex virus-infected cells.  PLoS ONE: 5(6): e10975.
  • Liu, M., B. Rakowski, E. Gershburg, C.M. Weisend, O. Lucas, E.E. Schmidt, and W.P. Halford.  2010.  ICP0 antagonizes ICP4-dependent silencing of the herpes simplex virus ICP0 gene.  PLoS ONE:  5(1): e8837. (Abstract)
  • Halford, W.P. 2007. Towards an effective herpes vaccine: past lessons and future prospects. Future Virology 2: 1-6. (Abstract)
  • Halford, W.P., J. Grace, C. Weisend, M. Soboleski, D.J.J. Carr, J.W. Balliet, Y. Imai, T.P. Margolis, and B.M. Gebhardt. 2006. ICP0 antagonizes Stat 1-dependent repression of herpes simplex virus: implications for the regulation of viral latency. Virol. J. 3: 44 (Abstract)
  • Halford, W.P. and P.A. Schaffer. 2001. ICP0 is required for the efficient reactivation of herpes simplex virus type 1 from neuronal latency. J. Virol. 75: 3240-3249. (Abstract)