Xiao Chong, Jin Huali, Hu Yanxin, Kang Youmin, Wang Junpeng, Du Xiaogang, Yang Yu, She Ruiping, Wang Bin
State Key Laboratory for Agro-Biotechnology and the Key Laboratory of Agro-Microbial Resources and Applications of MOA, China Agricultural University, Beijing 100094, China.
Antiviral Res. 2007 Oct;76(1):11-20. doi: 10.1016/j.antiviral.2007.04.002. Epub 2007 May 21.
To improve efficacy of DNA vaccination, various approaches have been developed, including the use of plasmid expressing co-stimulatory molecules as molecular adjuvants. In this study, we investigated whether co-inoculation of a construct expressing either 4-1BBL or OX40L as the molecular adjuvant with FMDV DNA vaccine, pcD-VP1, can increase immune responses and protective efficacies. Compared to the group immunized with pcD-VP1 alone, the co-inoculation of either molecular adjuvant induced a higher ratio of IgG2a/IgG1, higher levels of expression of IFN-gamma in CD4(+) and CD8(+) T cells and antigen-specific CTL responses, and more importantly provided an enhanced protection against the live FMDV challenge in animals. Concurrently, 4-1BBL as the molecular adjuvant dramatically reduced the viral loads of FMDV in vivo after the challenge. Together, the results demonstrate that co-stimulatory molecules 4-1BBL and OX40L can enhance the antigen-specific cell-mediated responses elicited by VP1 DNA vaccine and provide an enhanced protective efficacy with the reduced viral loads.
为提高DNA疫苗的效力,已开发出多种方法,包括使用表达共刺激分子的质粒作为分子佐剂。在本研究中,我们调查了将表达4-1BBL或OX40L作为分子佐剂的构建体与口蹄疫病毒DNA疫苗pcD-VP1共同接种,是否能增强免疫反应和保护效力。与单独用pcD-VP1免疫的组相比,两种分子佐剂的共同接种诱导了更高的IgG2a/IgG1比率、CD4(+)和CD8(+) T细胞中更高水平的IFN-γ表达以及抗原特异性CTL反应,更重要的是,在动物中提供了针对口蹄疫病毒活病毒攻击的增强保护。同时,4-1BBL作为分子佐剂在攻击后显著降低了体内口蹄疫病毒的病毒载量。总之,结果表明共刺激分子4-1BBL和OX40L可增强VP1 DNA疫苗引发的抗原特异性细胞介导反应,并在降低病毒载量的情况下提供增强的保护效力。