Attenuated herpes simplex virus 1 (HSV-1) expressing a mutant form of ICP6 stimulates a strong immune response that protects mice against HSV-1-induced corneal disease

David J. Davido, Eleain M. Tu, Hong Wang, Maria Korom, Andreu Gazquez Casals, P. Jahnu Reddy, Heba H. Mostafa, Benjamin Combs, Steve D. Haenchen, Lynda A. Morrison

Research output: Contribution to journalArticlepeer-review

Abstract

We previously isolated a herpes simplex virus 1 (HSV-1) mutant, KOS-NA, that carries two nonsynonymous mutations in UL39, resulting in L393P and R950H amino acid substitutions in infected cell protein 6 (ICP6). Our published data studying KOS-NA pathogenesis strongly suggest that one of these ICP6 substitutions expressed from KOS-NA, R950H, severely impaired acute viral replication in the eyes and trigeminal ganglia of mice after inoculation onto the cornea and consequently impaired establishment and reactivation from latency. Because of its significant neuroattenuation, we tested KOS-NA as a potential prophylactic vaccine against HSV-1 in a mouse model of corneal infection. KOS-NA stimulated stronger antibody and T cell responses than a replication-competent ICP0-null mutant and a replication-incompetent ICP8-null mutant optimized for immunogenicity. Immunizations with the ICP0-, ICP8-, and KOS-NA viruses all reduced replication of wild-type HSV-1 challenge virus in the corneal epithelium to similar extents. Low immunizing doses of KOS-NA and the ICP8- virus, but not the ICP0- virus, protected mice against eyelid disease (blepharitis). Notably, only KOS-NA protected almost completely against corneal disease (keratitis) and greatly reduced latent infection by challenge virus. Thus, vaccination of mice with KOS-NA prior to corneal challenge provides significant protection against HSV-1-mediated disease of the eye, even at a very low immunizing dose. These results suggest that KOS-NA may be the foundation of an effective prophylactic vaccine to prevent or limit HSV-1 ocular diseases.

Original languageEnglish (US)
Article numbere01036-18
JournalJournal of virology
Volume92
Issue number17
DOIs
StatePublished - Sep 1 2018

Keywords

  • Cornea
  • HSV-1
  • Herpes simplex virus
  • ICP6
  • Immunization
  • Keratitis
  • Mutant
  • Ocular
  • Vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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