title: Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus.
abstract: BACKGROUND
  Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine.
  
  
  RESULTS
  We investigated the immunogenicity of an attenuated strain of vaccinia virus engineered to inactivate the N1L gene (vGK5). Using the intranasal route, this recombinant virus was 2 logs less virulent compared to the wildtype VACV-WR. Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs. VACV-specific antibodies were also detected in the sera of mice infected 3-5 months prior with the attenuated vGK5 virus. Finally, mice immunized with vGK5 were significantly protected when challenged with a lethal dose of VACV-WR.
  
  
  CONCLUSIONS
  These results indicate that the attenuated vGK5 virus protects against subsequent infection and suggest that the N1L protein limits the strength of the early antiviral CD8 T cell response following respiratory infection.
authors.affiliation: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA. anuja.mathew@umassmed.edu
authors.forename: Anuja
authors.initials: A
authors.lastname: Mathew
authors.forename: Joel
authors.initials: J
authors.lastname: O'Bryan
authors.forename: William
authors.initials: W
authors.lastname: Marshall
authors.forename: Girish J
authors.initials: GJ
authors.lastname: Kotwal
authors.forename: Masanori
authors.initials: M
authors.lastname: Terajima
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: C464479:N1L protein, Vaccinia virus; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines