Zeng Rui-hong, Gong Wei, Fan Chang-fa, Wang Yun-fei, Mei Xing-guo
Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Vaccine. 2006 Feb 13;24(7):941-7. doi: 10.1016/j.vaccine.2005.08.064. Epub 2005 Aug 30.
Respiratory syncytial virus (RSV), an important pathogen of the lower respiratory tract, is responsible for severe illness both in new born and young children and in elderly people. However, development of a RSV vaccine has been hampered by the outcome of the infant trials in the 1960s with a formalin-inactivated RSV (FI-RSV) preparation. Previous studies in mice indicated that G protein immunization resulted in antibody and Th2-type response and failed to induce MHC I-restricted CD8(+) T-cell response. Vaccines designed to induce CD8(+) T-cell along with antibody response might be ideal. In the present report, a fusion protein G1F/M2 containing a RSV-G protein fragment (G: 125-225 amino acid) and a CD8(+) T-cell epitope from RSV-M2 protein was investigated. G1F/M2 was cloned, expressed in E. coli, purified and renaturated. In BALB/c mice, G1F/M2 induced not only humoral immunity but also cellular immunity. In addition, interestedly, G1F/M2 elicited balanced IgG1/IgG2a response. These results suggest that the fusion protein G1F/M2 is potential as a RSV subunit vaccine.
呼吸道合胞病毒(RSV)是下呼吸道的一种重要病原体,可导致新生儿、幼儿和老年人患严重疾病。然而,20世纪60年代婴儿使用甲醛灭活RSV(FI-RSV)制剂进行的试验结果阻碍了RSV疫苗的研发。此前在小鼠身上进行的研究表明,G蛋白免疫可产生抗体和Th2型反应,但无法诱导MHC I类限制性CD8(+) T细胞反应。设计能够诱导CD8(+) T细胞反应以及抗体反应的疫苗可能是理想的。在本报告中,研究了一种包含RSV-G蛋白片段(G:125-225个氨基酸)和RSV-M2蛋白的CD8(+) T细胞表位的融合蛋白G1F/M2。G1F/M2被克隆、在大肠杆菌中表达、纯化并复性。在BALB/c小鼠中,G1F/M2不仅诱导了体液免疫,还诱导了细胞免疫。此外,有趣的是,G1F/M2引发了平衡的IgG1/IgG2a反应。这些结果表明,融合蛋白G1F/M2作为RSV亚单位疫苗具有潜力。