December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Therapeutic Immunization with a Virion Host Shutoff (vhs) Defective, Replication-Incompetent HSV-1 Strain Limits Recurrent Herpetic Ocular Infection
Author Affiliations & Notes
  • TL Keadle
    Department of Ophthalmology and Visual Sciences Washington University School of Medicine St Louis MO
  • LA Morrison
    Department of Molecular Microbiology and Immunology Saint Louis University St Louis MO
  • JL Morris
    Department of Ophthalmology and Visual Sciences Washington University School of Medicine St Louis MO
  • JS Pepose
    Pepose Vision Institute Chesterfield MO
  • PM Stuart
    Department of Ophthalmology and Visual Sciences Washington University School of Medicine St Louis MO
  • Footnotes
    Commercial Relationships   T.L. Keadle, None; L.A. Morrison, None; J.L. Morris, None; J.S. Pepose, None; P.M. Stuart, None. Grant Identification: Support: NIH Grant EY1188501A1
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 3854. doi:
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    • Get Citation

      TL Keadle, LA Morrison, JL Morris, JS Pepose, PM Stuart; Therapeutic Immunization with a Virion Host Shutoff (vhs) Defective, Replication-Incompetent HSV-1 Strain Limits Recurrent Herpetic Ocular Infection . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3854.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose:Immunization of mice with herpes simplex virus 1 (HSV-1) mutant viruses containing deletions in the virion host shutoff (vhs) gene induces protection against recurrent as well as primary corneal infection with wild type HSV-1. Vhs mutant viruses are severely attenuated in vivo, but establish latent infections in sensory neurons. A safer HSV-1 mutant vaccine strain, Δ;41/Δ;29, has combined vhs and replication (ICP8-) deficits, and provides protection to BALB/c mice against primary corneal infection equivalent to that of a vhs- strain (BGS41). Here, we tested the hypothesis that Δ;41/Δ;29 can protect as well as BGS41 in a therapeutic setting. Methods:Because immune response induction may vary with the mouse and virus strains studied, we first determined the effect of prophylactic Δ;41/Δ;29 vaccination on primary ocular infection of NIH inbred mice with HSV-1 McKrae-the same mouse/virus combination to be used in evaluating therapeutic vaccines. Accordingly, in prophylactic studies, mice were vaccinated with Δ;41/Δ;29 4 weeks prior to corneal challenge infection with HSV. In therapeutic studies, mice with latent ocular HSV infection were vaccinated with BGS41 or Δ;41/Δ;29 4 months after primary infection, and viral reactivation was induced by UV-B light 4 weeks later. Results:In a dose dependent fashion, prophylactic Δ;41/Δ;29 vaccination decreased post challenge tear film virus titers and ocular disease incidence and severity, while eliciting high levels of HSV-specific antibodies. Therapeutically, immunization with Δ;41/Δ;29 effectively reduced the incidence of UV-B-induced recurrent virus shedding in latently infected mice. Therapeutic Δ;41/Δ;29 and BGS41 immunization decreased corneal opacity while elevating antibody titers compared to control vaccine. Immunopathologic delayed type hypersensitivity responses were decreased in both vaccine groups. Conclusion: These data indicate that replication is not a prerequisite for the generation of therapeutic immunity by live HSV mutant virus vaccines, and raise the possibility that genetically tailored replication-defective viruses may make effective and safe therapeutic vaccine candidates.

Keywords: 425 herpes simplex virus • 370 cornea: basic science • 435 immunomodulation/immunoregulation 
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