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.
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.