Smith Mary Ellen, Koser Martin, Xiao Sa, Siler Catherine, McGettigan James P, Calkins Catherine, Pomerantz Roger J, Dietzschold Bernhard, Schnell Matthias J
Department of Microbiology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Virology. 2006 Sep 30;353(2):344-56. doi: 10.1016/j.virol.2006.05.010. Epub 2006 Jul 3.
Live viral vectors expressing foreign antigens have shown great promise as vaccines against viral diseases. However, safety concerns remain a major problem regarding the use of even highly attenuated viral vectors. Using the rabies virus (RV) envelope protein as a carrier molecule, we show here that inactivated RV particles can be utilized to present Bacillus anthracis protective antigen (PA) domain-4 in the viral membrane. In addition to the RV glycoprotein (G) transmembrane and cytoplasmic domains, a portion of the RV G ectodomain was required to express the chimeric RV G anthrax PA on the cell surface. The novel antigen was also efficiently incorporated into RV virions. Mice immunized with the inactivated recombinant RV virions exhibited seroconversion against both RV G and anthrax PA, and a second inoculation greatly increased these responses. These data demonstrate that a viral envelope protein can carry a bacterial protein and that a viral carrier can display whole polypeptides compared to the limited epitope presentation of previous viral systems.
表达外源抗原的活病毒载体作为抗病毒疾病疫苗已显示出巨大潜力。然而，即使是使用高度减毒的病毒载体，安全问题仍是一个主要问题。我们在此表明，利用狂犬病毒（RV）包膜蛋白作为载体分子，灭活的RV颗粒可用于在病毒膜上呈递炭疽芽孢杆菌保护性抗原（PA）结构域4。除了RV糖蛋白（G）的跨膜和胞质结构域外，还需要一部分RV G胞外结构域才能在细胞表面表达嵌合RV G炭疽PA。这种新型抗原也能有效地整合到RV病毒粒子中。用灭活的重组RV病毒粒子免疫的小鼠表现出针对RV G和炭疽PA的血清转化，二次接种大大增强了这些反应。这些数据表明，病毒包膜蛋白可以携带细菌蛋白，与以前病毒系统有限的表位呈递相比，病毒载体可以展示完整的多肽。
