Department of Medicine, Division of Infectious Diseases and Immunology; Center for Infectious Disease and Vaccine Research
Animals; B-Lymphocytes; CD8-Positive T-Lymphocytes; Mice; Mice, Inbred C57BL; Vaccines, Synthetic; Vaccinia virus; Viral Proteins; Viral Vaccines
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
BACKGROUND: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine.
METHODOLOGY AND PRINCIPAL FINDINGS: 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.
Rights and Permissions
Copyright: © 2008 Mathew et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Mathew A, O'Bryan J, Marshall W, Kotwal GJ, Terajima M, et al. (2008) Robust Intrapulmonary CD8 T Cell Responses and Protection with an Attenuated N1L Deleted Vaccinia Virus. PLoS ONE 3(10): e3323. doi:10.1371/journal.pone.0003323. Link to article on publisher's site
Mathew, Anuja; O'Bryan, Joel M.; Marshall, William L.; Kotwal, Girish J.; Terajima, Masanori; Green, Sharone; Rothman, Alan L.; and Ennis, Francis A., "Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus" (2008). Open Access Articles. 2370.