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在无菌猪模型中,初免/加强轮状病毒DNA疫苗诱导的黏膜和全身抗体反应及保护作用。

Mucosal and systemic antibody responses and protection induced by a prime/boost rotavirus-DNA vaccine in a gnotobiotic pig model.

作者信息

Yuan Lijuan, Azevedo Marli S P, Gonzalez Ana M, Jeong Kwang-il, Van Nguyen Trang, Lewis Peggy, Iosef Cristiana, Herrmann John E, Saif Linda J

机构信息

Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster OH 44691, USA.

出版信息

Vaccine. 2005 Jun 10;23(30):3925-36. doi: 10.1016/j.vaccine.2005.03.009. Epub 2005 Apr 9.

DOI:10.1016/j.vaccine.2005.03.009
PMID:15917114
Abstract

A live rotavirus prime/DNA boost vaccine regimen was evaluated in a gnotobiotic pig model for human rotavirus (HRV) diarrhea. Plasmid DNA expressing rotavirus inner capsid VP6 was administered to pigs intramuscularly (IM) twice after oral priming with attenuated (Att) Wa strain HRV (AttHRV/VP6DNA2x). Other groups included: (1) VP6 DNA IM 2x then AttHRV orally (VP6DNA2x/AttHRV); (2) VP6 DNA IM 3x (VP6DNA3x) and controls. Significant protection (70%) against virus shedding, but lower protection against diarrhea (30%) was achieved only in the AttHRV/VP6DNA2x group after challenge (virulent Wa HRV). The other vaccines (VP6DNA2x/AttHRV and VP6DNA3x) were less effective. Higher protection rates were associated with the highest IgA antibody responses induced by the AttHRV/VP6DNA2x regimen. Interestingly, the VP6 DNA vaccine, although not effective when administered alone, boosted neutralizing and VP4 antibody titers in pigs previously primed with AttHRV, possibly mediated by cross-reactive T helper cells.

摘要

在无菌猪模型中评估了一种活轮状病毒初免/DNA加强疫苗方案对人轮状病毒(HRV)腹泻的效果。在用减毒(Att)Wa株HRV进行口服初免后,向猪肌肉注射(IM)两次表达轮状病毒内衣壳VP6的质粒DNA(AttHRV/VP6DNA2x)。其他组包括:(1)先肌肉注射VP6 DNA两次,然后口服AttHRV(VP6DNA2x/AttHRV);(2)肌肉注射VP6 DNA三次(VP6DNA3x)以及对照组。攻毒(强毒株Wa HRV)后,仅AttHRV/VP6DNA2x组对病毒排泄有显著保护作用(70%),但对腹泻的保护作用较低(30%)。其他疫苗(VP6DNA2x/AttHRV和VP6DNA3x)效果较差。较高的保护率与AttHRV/VP6DNA2x方案诱导的最高IgA抗体反应相关。有趣的是,VP6 DNA疫苗虽然单独使用时无效,但能提高先前用AttHRV初免的猪的中和抗体和VP4抗体滴度,这可能由交叉反应性T辅助细胞介导。

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