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减毒 NYCBH 牛痘病毒缺失了免疫逃逸基因 E3L,可完全保护小鼠免受异源水疱性口炎病毒的攻击。

The attenuated NYCBH vaccinia virus deleted for the immune evasion gene, E3L, completely protects mice against heterologous challenge with ectromelia virus.

机构信息

Biodesign Institute, Arizona State University, Tempe, AZ 85287-5401, USA.

出版信息

Vaccine. 2011 Dec 6;29(52):9691-6. doi: 10.1016/j.vaccine.2011.09.108. Epub 2011 Oct 5.

DOI:10.1016/j.vaccine.2011.09.108
PMID:21983358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5001685/
Abstract

The New York City Board of Health (NYCBH) vaccinia virus (VACV) vaccine strain was deleted for the immune evasion gene, E3L, and tested for its pathogenicity and ability to protect mice from heterologous challenge with ectromelia virus (ECTV). NYCBHΔE3L was found to be highly attenuated for pathogenicity in a newborn mouse model and showed a similar attenuated phenotype as the NYVAC strain of vaccinia virus. Scarification with one or two doses of the attenuated NYCBHΔE3L was able to protect mice equally as well as NYCBH from death, weight loss, and viral spread to visceral organs. A single dose of NYCBHΔE3L resulted in low poxvirus-specific antibodies, and a second dose increased levels of poxvirus-specific antibodies to a level similar to that seen in animals vaccinated with a single dose of NYCBH. However, similar neutralizing antibody titers were observed following one or two doses of NYCBHΔE3L or NYCBH. Thus, NYCBHΔE3L shows potential as a candidate for a safer human smallpox vaccine since it protects mice from challenge with a heterologous poxvirus.

摘要

纽约市卫生局(NYCBH)的牛痘病毒(VACV)疫苗株被删除了免疫逃逸基因 E3L,并对其致病性和保护小鼠免受异源挑战的能力进行了测试。在新生小鼠模型中,NYCBHΔE3L 被发现对致病性高度减毒,表现出与 NYVAC 株牛痘病毒相似的减毒表型。在划伤时使用一剂或两剂减毒的 NYCBHΔE3L 能够像 NYCBH 一样有效地保护小鼠免受死亡、体重减轻和病毒传播到内脏器官的影响。一剂 NYCBHΔE3L 导致低水平的痘病毒特异性抗体,第二剂增加了痘病毒特异性抗体的水平,与单次接种 NYCBH 的动物相似。然而,在接种 NYCBHΔE3L 或 NYCBH 一剂或两剂后,观察到相似的中和抗体滴度。因此,NYCBHΔE3L 有望成为一种更安全的人类天花疫苗候选物,因为它可以保护小鼠免受异源痘病毒的挑战。

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本文引用的文献

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Ectromelia virus infections of mice as a model to support the licensure of anti-orthopoxvirus therapeutics.以小鼠的细小病毒感染为模型支持抗正痘病毒治疗药物的许可。
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Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: scarification vaccination.E3L基因发生突变的痘苗病毒作为具有潜在复制能力的减毒疫苗:划痕接种疫苗。
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