robust intrapulmonary cd8 t cell responses and protection with an attenuated n1l deleted vaccinia virus健壮的肺内的cd8 t细胞反应和保护具有减毒n1l牛痘病毒删除.pdfVIP

Robust Intrapulmonary CD8 T Cell Responses and Protection with an Attenuated N1L Deleted Vaccinia Virus 1 1 2 2 1 Anuja Mathew *, Joel O’Bryan , William Marshall , Girish J. Kotwal , Masanori Terajima , Sharone 1 1 1 Green , Alan L. Rothman , Francis A. Ennis 1 Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 2 Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America Abstract 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. Citation: Mathew A, O’Bryan J, M