Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus.
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.
Mathew
Anuja
A
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA. anuja.mathew@umassmed.edu
O'Bryan
Joel
J
Marshall
William
W
Kotwal
Girish J
GJ
Terajima
Masanori
M
Green
Sharone
S
Rothman
Alan L
AL
Ennis
Francis A
FA
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
C464479:N1L protein, Vaccinia virus; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines