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以共刺激分子作为分子佐剂的口蹄疫DNA疫苗增强了保护效力并降低了病毒载量。

Enhanced protective efficacy and reduced viral load of foot-and-mouth disease DNA vaccine with co-stimulatory molecules as the molecular adjuvants.

作者信息

Xiao Chong, Jin Huali, Hu Yanxin, Kang Youmin, Wang Junpeng, Du Xiaogang, Yang Yu, She Ruiping, Wang Bin

机构信息

State Key Laboratory for Agro-Biotechnology and the Key Laboratory of Agro-Microbial Resources and Applications of MOA, China Agricultural University, Beijing 100094, China.

出版信息

Antiviral Res. 2007 Oct;76(1):11-20. doi: 10.1016/j.antiviral.2007.04.002. Epub 2007 May 21.

Abstract

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.

摘要

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。

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