Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus.

Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus.
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DOI:
10.1371/journal.pone.0003323
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发表时间:
2008-10-02
期刊:
影响因子:
3.7
通讯作者:
Ennis FA
Ennis FA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mathew A;O'Bryan J;Marshall W;Kotwal GJ;Terajima M;Green S;Rothman AL;Ennis FA

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牛痘病毒已被用作病毒性疾病的模型和保护性活疫苗。我们研究了一种减毒株的免疫原性的牛痘病毒工程改造,以消除N1 L基因(vGK 5)。使用鼻内途径,与野生型VACV-WR相比,该重组病毒的毒力低2个对数。通过鼻内、腹膜内和尾部划痕途径的感染导致脾和肺中溶细胞病毒特异性CD 8 T细胞的稳健诱导。在用减毒vGK 5病毒感染前3-5个月的小鼠血清中也检测到VACV特异性抗体。最后,当用致死剂量的VACV-WR攻击时,用vGK 5免疫的小鼠受到显著保护。这些结果表明,减毒的vGK 5病毒保护免受随后的感染,并表明N1 L蛋白限制了呼吸道感染后早期抗病毒CD 8 T细胞应答的强度。
Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine. 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. 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.
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