Li Wenfang, Ye Ling, Carrion Ricardo, Mohan Gopi S, Nunneley Jerritt, Staples Hilary, Ticer Anysha, Patterson Jean L, Compans Richard W, Yang Chinglai
Department of Microbiology and Immunology Emory Vaccine Center, Emory University, Atlanta, Georgia.
Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio.
J Infect Dis. 2015 Oct 1;212 Suppl 2(Suppl 2):S398-403. doi: 10.1093/infdis/jiv186. Epub 2015 Apr 14.
In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed "antigenic subversion." To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection.
除了其表面糖蛋白（GP）外，埃博拉病毒还指导产生大量截短的糖蛋白异构体（sGP），这些异构体被分泌到细胞外空间。我们最近报道，sGP会主动转移宿主针对其与GP共有的表位的抗体反应，从而使自身能够吸收抗GP抗体，我们将这一现象称为“抗原颠覆”。为了研究sGP的抗原颠覆对预防病毒感染的影响，我们比较了在小鼠中用GP和sGP DNA疫苗进行不同的初免-加强免疫方案诱导的免疫反应及其对致死性埃博拉病毒攻击的效力。用sGP和GP DNA疫苗进行两次免疫诱导的抗GP抗体水平相似。然而，用GP而非sGP DNA疫苗进行两次免疫可使小鼠完全免受致死性攻击。在已用GP或sGP DNA疫苗进行初免的小鼠中，用sGP或GP DNA疫苗进行加强免疫可提高抗GP抗体反应水平，并进一步提高对埃博拉病毒感染的保护效力。这些结果表明，抗GP抗体反应的质量和水平均会影响对埃博拉病毒感染的保护效力。
