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Intramuscular delivery of replication-defective herpes simplex virus gives antigen expression in muscle syncytia and improved protection against pathogenic HSV-2 strains.

Authors
  • Diaz, Fernando1
  • Gregory, Sean1
  • Nakashima, Hiroshi2
  • Viapiano, Mariano S2
  • Knipe, David M3
  • 1 Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States. , (United States)
  • 2 Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA,United States. , (United States)
  • 3 Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Virology
Publisher
Elsevier
Publication Date
Jan 01, 2018
Volume
513
Pages
129–135
Identifiers
DOI: 10.1016/j.virol.2017.10.011
PMID: 29069622
Source
Medline
Keywords
License
Unknown

Abstract

Herpes simplex virus 2 (HSV-2) is the leading cause of genital herpes and increases the risk of HIV infection, but there is no effective vaccine. A replication-defective HSV-2 mutant virus, dl5-29, is effective in animal models and has been in a phase I trial. Previous studies have shown that dl5-29 gives higher antibody responses and better protection when inoculated intramuscularly (IM) as compared with subcutaneously (SC). However, the basis for this effect has not been defined. We confirmed that IM inoculation of dl5-29 is more immunogenic and provides better protection than SC inoculation. IM inoculation of HSV-2 strains produced higher levels of a luciferase transgene than SC inoculation, as measured by intravital bioluminescence imaging. Intramuscular immunization also showed better protection against infection with a highly pathogenic African HSV-2, demonstrating that this single vaccine can be efficacious against HSV-2 strains from different geographic regions.

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