Therapeutic immunization with a virion host shutoff-defective, replication-incompetent herpes simplex virus type 1 strain limits recurrent herpetic ocular infection

Journal of Virology
T L KeadlePatrick M Stuart

Abstract

Immunization of mice with herpes simplex virus type 1 (HSV-1) mutant viruses containing deletions in the gene for virion host shutoff (vhs) protein diminishes primary and recurrent 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, Delta41Delta29, has combined vhs and replication (ICP8-) deficits and protects BALB/c mice against primary corneal infection equivalent to a vhs- strain (BGS41). Here, we tested the hypothesis that Delta41Delta29 can protect as well as BGS41 in a therapeutic setting. Because immune response induction varies with the mouse and virus strains studied, we first determined the effect of prophylactic Delta41Delta29 vaccination on primary ocular infection of NIH inbred mice with HSV-1 McKrae, a model system used to evaluate therapeutic vaccines. In a dose-dependent fashion, prophylactic Delta41Delta29 vaccination decreased postchallenge tear film virus titers and ocular disease incidence and severity while eliciting high levels of HSV-specific antibodies. Adoptive transfer studies demonstrated a dominant role for immune serum and a lesser role for immune cells in mediating prophyl...Continue Reading

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Citations

May 14, 2010·Journal of Virology·Christian Andreas MohrTorsten Sacher
May 18, 2012·Clinical & Developmental Immunology·Patrick M Stuart, Tammie L Keadle
Oct 28, 2015·Journal of Immunology Research·Xiao-Tang YinPatrick M Stuart
Sep 22, 2006·The Journal of Gene Medicine·M W HaltermanH J Federoff
Jun 26, 2004·The Journal of General Virology·Patrick M StuartDavid A Leib
Dec 14, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica E MorrisPatrick M Stuart
Jan 21, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Devin M WestPatrick M Stuart

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