Both G W, Lockett L J, Janardhana V, Edwards S J, Bellamy A R, Graham F L, Prevec L, Andrew M E
CSIRO Division of Biomolecular Engineering, North Ryde, NSW, Australia.
Virology. 1993 Apr;193(2):940-50. doi: 10.1006/viro.1993.1203.
VP7sc is a novel rotavirus antigen engineered for presentation at the cell surface. Several recombinant viruses were constructed in which VP7sc was inserted into the E3 region of the human type 5 adenovirus (Ad5) genome and expression and transport of the antigen was monitored in cultured 293 cells. The recombinant virus showing the greatest level of expression (Ad5/7.4) was then used to determine whether antibodies to VP7sc could be induced in a nonhuman host. BALB/c and CBA/H mice were inoculated with Ad5/7.4 by iv, ip, oral and intranasal routes and serum antibody levels were assayed by ELISA. All vaccinated animals seroconverted but, depending on the route of vaccination, not all animals showed a significant secondary response following re-inoculation. The ability of Ad5/7.4 to induce protective immunity in mice was also examined using several vaccination regimes. A single dose of Ad5/7.4 given intranasally to dams not previously exposed to rotavirus was sufficient to induce immunity which could be passively transferred to protect suckling neonates. Recombinant adenoviruses expressing protective antigens therefore may provide an alternative to the use of attenuated rotaviruses in the development of a vaccine against gastroenteritis.
VP7sc是一种经过改造可在细胞表面呈递的新型轮状病毒抗原。构建了几种重组病毒,其中VP7sc被插入人5型腺病毒(Ad5)基因组的E3区域,并在培养的293细胞中监测该抗原的表达和转运。然后使用表达水平最高的重组病毒(Ad5/7.4)来确定是否能在非人类宿主中诱导产生针对VP7sc的抗体。通过静脉内、腹腔内、口服和鼻内途径用Ad5/7.4接种BALB/c和CBA/H小鼠,并通过ELISA检测血清抗体水平。所有接种疫苗的动物都发生了血清转化,但根据接种途径的不同,并非所有动物在再次接种后都表现出显著的二次反应。还使用几种接种方案研究了Ad5/7.4在小鼠中诱导保护性免疫的能力。给先前未接触过轮状病毒的母鼠鼻内接种单剂量的Ad5/7.4足以诱导产生免疫力,这种免疫力可被动转移以保护哺乳的新生儿。因此,表达保护性抗原的重组腺病毒可能为开发抗胃肠炎疫苗时使用减毒轮状病毒提供一种替代方法。