Vaccinating with conserved Escherichia coli antigens does not alter the mouse intestinal microbiome.

Vaccinating with conserved Escherichia coli antigens does not alter the mouse intestinal microbiome.
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DOI:
10.1186/s13104-016-2208-y
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发表时间:
2016-08-11
期刊:
影响因子:
1.8
通讯作者:
Hardwidge PR
Hardwidge PR
中科院分区:
其他
文献类型:
--
作者:
Hays MP;Ericsson AC;Yang Y;Hardwidge PR

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产肠毒素大肠杆菌(ETEC)可引起腹泻病。ETEC定植因子的抗原和结构异质性使疫苗开发工作复杂化。因此,鉴定和表征诱导保护性免疫的保守ETEC抗原是有意义的。我们先前表征了三种蛋白质(MipA、Skp和ETEC_2479),这些蛋白质在接种疫苗后在鼻内ETEC攻击模型中保护小鼠。然而,这些蛋白质不仅在多种ETEC分离株中是保守的,而且在大肠杆菌中也是保守的。虽然已经研究了灭活病毒疫苗和减毒活细菌疫苗对宿主微生物群的影响,但尚未研究使用由也由寄生生物编码的抗原组成的亚单位疫苗的潜在影响。我们通过表征小鼠肠道微生物组的变化作为疫苗接种的函数来解决这个问题。我们未能观察到小鼠健康的显著变化,小鼠体重增加作为时间的函数,或小鼠肠道微生物组的多样性或丰富性,如通过分析α和β多样性以及整体群落结构所测量的,在接种疫苗之前和之后。我们得出结论,尽管革兰氏阴性菌中MipA、Skp和ETEC_2479保守,但接种这些抗原未能显著改变宿主肠道微生物组。
Enterotoxigenic Escherichia coli (ETEC) causes diarrheal disease. Antigenic and structural heterogeneity among ETEC colonization factors has complicated vaccine development efforts. Identifying and characterizing conserved ETEC antigens that induce protective immunity is therefore of interest. We previously characterized three proteins (MipA, Skp, and ETEC_2479) that protected mice in an intranasal ETEC challenge model after vaccination. However, these proteins are conserved not only in multiple ETEC isolates, but also in commensal bacteria. While the impact of inactivated viral vaccines and live-attenuated bacterial vaccines on the host microbiota have been examined, the potential impact of using subunit vaccines consisting of antigens that are also encoded by commensal organisms has not been investigated. We addressed this issue by characterizing changes to mouse intestinal microbiomes as a function of vaccination. We failed to observe significant changes to mouse health, to mouse weight gain as a function of time, or to the diversity or richness of mouse intestinal microbiomes, as measured by analyzing alpha- and beta-diversity, as well as overall community structure, before and after vaccination. We conclude that despite the conservation of MipA, Skp, and ETEC_2479 among Gram-negative bacteria, vaccination with these antigens fails to alter significantly the host intestinal microbiome.