Ulmer J B, Donnelly J J, Parker S E, Rhodes G H, Felgner P L, Dwarki V J, Gromkowski S H, Deck R R, DeWitt C M, Friedman A
Department of Cancer Research, Merck Research Laboratories, West Point, PA 19486.
Science. 1993 Mar 19;259(5102):1745-9. doi: 10.1126/science.8456302.
Cytotoxic T lymphocytes (CTLs) specific for conserved viral antigens can respond to different strains of virus, in contrast to antibodies, which are generally strain-specific. The generation of such CTLs in vivo usually requires endogenous expression of the antigen, as occurs in the case of virus infection. To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleoprotein was injected into the quadriceps of BALB/c mice. This resulted in the generation of nucleoprotein-specific CTLs and protection from a subsequent challenge with a heterologous strain of influenza A virus, as measured by decreased viral lung titers, inhibition of mass loss, and increased survival.
与通常具有毒株特异性的抗体不同,针对保守病毒抗原的细胞毒性T淋巴细胞(CTL)能够对不同毒株的病毒作出反应。在体内产生此类CTL通常需要抗原的内源性表达,病毒感染时就是如此。为了在不受直接肽递送或病毒载体限制的情况下产生一种可呈递给免疫系统的病毒抗原,将编码甲型流感病毒核蛋白的质粒DNA注射到BALB/c小鼠的股四头肌中。通过降低肺部病毒滴度、抑制体重减轻和提高生存率来衡量,这导致了核蛋白特异性CTL的产生以及对随后甲型流感病毒异源毒株攻击的保护作用。