1887

Journal of General Virology

Volume 83, Issue 10

Therapeutic vaccination with vhs herpes simplex virus reduces the severity of recurrent herpetic stromal keratitis in mice Free

Abstract

Virion host shutoff (vhs)-deficient herpes simplex virus (HSV) was tested as a therapeutic vaccine in a mouse model of UV light-induced recurrent herpetic stromal keratitis. Four weeks after primary corneal infection, mice were vaccinated intraperitoneally with vhs vaccine or control. Four weeks after vaccination, the eyes of latently infected mice were UV-B irradiated to induce recurrent virus shedding and disease. Post-irradiation corneal opacity in latently infected, vhs-vaccinated mice was significantly reduced compared to control-vaccinated mice (=0·007 to 0·035). The incidence and duration of recurrent virus shedding were the same in both groups. Antibody titres were increased (=0·05) and delayed type hypersensitive responses were unaffected by vhs vaccination. Combined with studies using different vaccination timing and vhs genotypes, these data suggest that deletion of vhs is a useful strategy in the development of a therapeutic HSV vaccine, and that temporal and genetic factors influence vaccination outcome.

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© Microbiology Society
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2002-10-01
2020-01-27
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References

  1. Brubaker, J. O., Thompson, C. M., Morrison, L. A., Knipe, D. M., Siber, G. R. & Finberg, R. W. ( 1996; ). Induction of Th1-associated immune responses to beta-galactosidase expressed by a replication-defective mutant of herpes simplex virus 1. Journal of Immunology 157, 1598-1604.
     [Google Scholar]
  2. Daheshia, M., Kuklin, N., Kannangat, S., Manickan, E. & Rouse, B. T. ( 1997; ). Suppression of ongoing ocular inflammatory disease by topical administration of plasmid DNA encoding IL-10. Journal of Immunology 159, 1945-1952.
     [Google Scholar]
  3. Deshpande, S. P., Kumaraguru, U. & Rouse, B. T. ( 2000; ). Why do we lack an effective vaccine against herpes simplex virus infections? Microbes and Infection 2, 973-978.[CrossRef]
    [Google Scholar]
  4. Geiss, B. J., Smith, T. J., Leib, D. A. & Morrison, L. A. ( 2000; ). Disruption of virion host shutoff activity improves the immunogenicity and protective capacity of a replication-incompetent herpes simplex virus type 1 vaccine strain. Journal of Virology 74, 11137-11144.[CrossRef]
    [Google Scholar]
  5. Keadle, T. L., Laycock, K. A., Miller, J. K., Hook, K. K., Fenoglio, E. D., Francotte, M., Slaoui, M., Stuart, P. M. & Pepose, J. S. ( 1997; ). Efficacy of a recombinant glycoprotein D subunit vaccine on the development of primary and recurrent ocular infection with herpes simplex virus type 1 in mice. Journal of Infectious Diseases 176, 331-338.[CrossRef]
    [Google Scholar]
  6. Keadle, T. L., Usui, N., Laycock, K. A., Kumano, Y., Pepose, J. S. & Stuart, P. M. ( 2001; ). Cytokine expression in murine corneas during recurrent herpetic stromal keratitis. Ocular Immunology and Inflammation 9, 193-205.[CrossRef]
    [Google Scholar]
  7. Keadle, T. L., Morrison, L. A., Morris, J. L., Pepose, J. S. & Stuart, P. M. ( 2002; ). Therapeutic immunization with a virion host shutoff-defective, replication-incompetent herpes simplex virus type 1 strain limits recurrent herpetic ocular infection. Journal of Virology 76, 3615-3625.[CrossRef]
    [Google Scholar]
  8. Kwong, A. D. & Frenkel, N. ( 1987; ). Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs. Proceedings of the National Academy of Sciences, USA 84, 1926-1930.[CrossRef]
    [Google Scholar]
  9. Lausch, R. N., Kleinschrodt, W. R., Monteiro, C., Kayes, S. G. & Oakes, J. E. ( 1985; ). Resolution of HSV corneal infection in the absence of delayed-type hypersensitivity. Investigative Ophthalmology & Visual Science 26, 1509-1515.
     [Google Scholar]
  10. Laycock, K. A., Lee, S. F., Brady, R. H. & Pepose, J. S. ( 1991; ). Characterization of a murine model of recurrent herpes simplex viral keratitis induced by ultra violet B radiation. Investigative Ophthalmology & Visual Science 32, 2741-2746.
     [Google Scholar]
  11. Liu, T., Khanna, K. M., Chen, X., Fink, D. J. & Hendricks, R. L. ( 2000; ). CD8+ T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons. Journal of Experimental Medicine 191, 1459-1466.[CrossRef]
    [Google Scholar]
  12. Miller, J. K., Laycock, K. A., Umphress, J. A., Hook, K. K., Stuart, P. M. & Pepose, J. S. ( 1996; ). A comparison of recurrent and primary herpes simplex keratitis in NIH inbred mice. Cornea 15, 497-504.
     [Google Scholar]
  13. Nesburn, A. B., Burke, R. L., Ghiasi, H., Slanina, S. M. & Wechsler, S. L. ( 1998; ). A therapeutic vaccine that reduces recurrent herpes simplex virus type 1 corneal disease. Investigative Ophthalmology & Visual Science 39, 1163-1170.
     [Google Scholar]
  14. Niemialtowski, M. G. & Rouse, B. T. ( 1992; ). Predominance of Th1 cells in ocular tissue during herpetic stromal keratitis. Journal of Immunology 149, 3035-3039.
     [Google Scholar]
  15. Pepose, J. S., Leib, D. A., Stuart, P. M. & Easty, E. L. ( 1996; ). Herpes simplex virus diseases: anterior segment of the eye. In Ocular Infection and Immunity , pp. 905-932. Edited by J. S. Pepose, G. A. N. Holland & K. R. Wilhelmus. St Louis, MO:Mosby.
  16. Pivetti-Pezzi, P., Accorinti, M., Colabelli-Gisoldi, R. A., Pirraglia, M. P. & Sirianni, M. C. ( 1999; ). Herpes simplex virus vaccine in recurrent ocular infection. Cornea 18, 47-51.[CrossRef]
    [Google Scholar]
  17. Russell, R. G., Nasisse, M. P., Larsen, H. S. & Rouse, B. T. ( 1984; ). Role of T-lymphocytes in the pathogenesis of herpetic stromal keratitis. Investigative Ophthalmology & Visual Science 25, 938-944.
     [Google Scholar]
  18. Shimeld, C., Hill, T. & Easty, D. ( 1989; ). An improved model of recurrent herpetic eye disease in mice. Current Eye Research 8, 1193-1205.[CrossRef]
    [Google Scholar]
  19. Shimeld, C., Hill, T., Blyth, W. A. & Easty, D. L. ( 1990; ). Passive immunization protects the mouse eye from damage after herpes simplex virus infection by limiting spread of virus in the nervous system. Journal of General Virology 71, 681-687.[CrossRef]
    [Google Scholar]
  20. Smith, T. J., Morrison, L. A. & Leib, D. A. ( 2002; ). Pathogenesis of herpes simplex virus type 2 virion host shutoff (vhs) mutants. Journal of Virology 76, 2054-2061.[CrossRef]
    [Google Scholar]
  21. Stanberry, L. R., Cunningham, A. L., Mindel, A., Scott, L. L., Spruance, S. L., Aoki, F. Y. & Lacey, C. J. ( 2000; ). Prospects for control of herpes simplex virus disease through immunization. Clinical Infectious Diseases 30, 549-566.[CrossRef]
    [Google Scholar]
  22. Strelow, L. I. & Leib, D. A. ( 1995; ). Role of the virion host shutoff (vhs) of herpes simplex virus type 1 in latency and pathogenesis. Journal of Virology 69, 6779-6786.
     [Google Scholar]
  23. Stumpf, T. H., Shimeld, C., Easty, D. L. & Hill, T. J. ( 2001; ). Cytokine production in a murine model of recurrent herpetic stromal keratitis. Investigative Ophthalmology & Visual Science 42, 372-378.
     [Google Scholar]
  24. Tigges, M. A., Leng, S., Johnson, D. C. & Burke, R. L. ( 1996; ). Human herpes simplex virus (HSV)-specific CD8+ CTL clones recognize HSV-2 infected fibroblasts after treatment with IFN-gamma or when virion host shutoff functions are disabled. Journal of Immunology 156, 3901-3910.
     [Google Scholar]
  25. Tumpey, T. M., Elner, V. M., Chen, S., Oakes, J. E. & Lausch, R. N. ( 1994; ). Interleukin-10 treatment can suppress stromal keratitis induced by herpes simplex virus type 1. Journal of Immunology 153, 2258-2265.
     [Google Scholar]
  26. Walker, J. & Leib, D. A. ( 1998; ). Protection from primary infection and establishment of latency by vaccination with a herpes simplex virus type 1 recombinant deficient in virion host shutoff (vhs) function. Vaccine 16, 1-5.[CrossRef]
    [Google Scholar]
  27. Walker, J., Laycock, K. A., Pepose, J. S. & Leib, D. A. ( 1998; ). Post exposure vaccination with a virion host shutoff defective mutant reduces UV-B radiation-induced ocular herpes simplex virus shedding in mice. Vaccine 16, 6-8.[CrossRef]
    [Google Scholar]
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Therapeutic vaccination with vhs− herpes simplex virus reduces the severity of recurrent herpetic stromal keratitis in mice
J. Gen. Virol. 83, 2361 (2002); https://doi.org/10.1099/0022-1317-83-10-2361
/content/journal/jgv/10.1099/0022-1317-83-10-2361
/content/journal/jgv/10.1099/0022-1317-83-10-2361
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