Jentarra Garilyn M, Heck Michael C, Youn Jin Won, Kibler Karen, Langland Jeffrey O, Baskin Carole R, Ananieva Olga, Chang Yung, Jacobs Bertram L
Graduate Program in Molecular and Cellular Biology, Arizona State University, United States.
Vaccine. 2008 Jun 2;26(23):2860-72. doi: 10.1016/j.vaccine.2008.03.044. Epub 2008 Apr 8.
In this study, we evaluated the efficacy of vaccinia virus (VACV) containing mutations in the E3L virulence gene to protect mice against a lethal poxvirus challenge after vaccination by scarification. VACV strains with mutations in the E3L gene had significantly decreased pathogenicity, even in immune deficient mice, yet retained the ability to produce a potent Th1-dominated immune response in mice after vaccination by scarification, while protecting against challenge with wild type, pathogenic VACV. Initial experiments were done using the mouse-adapted, neurovirulent Western Reserve (WR) strain of vaccinia virus. Testing of the full E3L deletion mutation in the Copenhagen and NYCBH strains of VACV, which are more appropriate for use in humans, produced similar results. These results suggest that highly attenuated strains of VACV containing mutations in E3L have the potential for use as scarification administered vaccines.
在本研究中,我们评估了E3L毒力基因发生突变的痘苗病毒(VACV)在通过划痕接种进行疫苗接种后保护小鼠免受致死性痘病毒攻击的效力。E3L基因发生突变的VACV毒株致病性显著降低,即便在免疫缺陷小鼠中也是如此,但在通过划痕接种进行疫苗接种后,仍保留了在小鼠体内产生以Th1为主导的强效免疫反应的能力,同时能抵御野生型致病性VACV的攻击。最初的实验使用的是适应小鼠的、具有神经毒性的痘苗病毒西储(WR)株。对更适合用于人类的VACV哥本哈根株和NYCBH株中的E3L完全缺失突变进行测试,也产生了类似结果。这些结果表明,E3L发生突变的高度减毒VACV毒株有潜力用作通过划痕接种方式给药的疫苗。