期刊
NPJ VACCINES
卷 4, 期 -, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41541-019-0137-1
关键词
-
资金
- NIH/NIDCD [R01 DC011818]
- NIH/NIAID [N01 AI-30040]
The chronicity and recurrence of many bacterial diseases is largely attributable to the presence of a biofilm, and eradication of these structures is confounded by an extracellular DNA-rich matrix. DNABII proteins, including integration host factor (IHF), are critical components of the matrix formed by all human pathogens tested to date. Whereas the natural adaptive immune response to IHF is against non-protective epitopes within the carboxyl-terminal region, antibodies against the DNA-binding tips induce biofilm collapse. We designed a tip-chimer immunogen to mimic the DNA-binding regions within the alpha-subunit and beta-subunit of IHF from nontypeable Haemophilus influenzae (IHFNTHi). Re-direction of the natural adaptive immune response toward immunoprotective domains disrupted NTHi biofilms in vitro and in an experimental model of otitis media. Our data support the rational design of a powerful therapeutic approach, and also that of a DNABII-directed vaccine antigen that would avoid augmentation of any pre-existing natural, but nonprotective, immune response.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据