Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus.

Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus.
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DOI:
10.1038/mi.2011.30
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发表时间:
2011-11
期刊:
影响因子:
8
通讯作者:
--
中科院分区:
医学1区
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--
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大多数艾滋病毒在女性中的传播是通过宫颈阴道粘膜进行的,宫颈阴道粘膜上覆盖着包括乳杆菌在内的细菌生物膜。这种肠道细菌在维持健康的粘膜中起作用,可以通过基因工程产生抗病毒肽。在这里,我们报告了63%的嵌合猴/人类免疫缺陷病毒(SHIVSF 162 P3)的传播减少后,反复阴道挑战的猕猴与表达HIV-1进入抑制剂cyanovirin-N的詹氏乳杆菌治疗。此外,突破性感染的定殖猕猴中的峰值病毒载量降低了6倍。基因工程乳酸杆菌的定殖和延长的抗病毒蛋白分泌不会引起促炎标志物的任何增加。这些发现为减少女性艾滋病毒异性传播的可获得和持久的方法奠定了基础,该方法独立于性交,价格低廉,并增强了阴道微生物群落的自然保护作用。
Most HIV transmission in women occurs through the cervicovaginal mucosa, which is coated by a bacterial biofilm including Lactobacillus. This commensal bacterium plays a role in maintaining healthy mucosa and can be genetically engineered to produce anti-viral peptides. Here, we report a 63% reduction in transmission of a chimeric simian/human immunodeficiency virus (SHIVSF162P3) after repeated vaginal challenges of macaques treated with Lactobacillus jensenii expressing the HIV-1 entry inhibitor cyanovirin-N. Furthermore, peak viral loads in colonized macaques with breakthrough infection were reduced 6-fold. Colonization and prolonged anti-viral protein secretion by the genetically engineered lactobacilli did not cause any increase in proinflammatory markers. These findings lay the foundation for an accessible and durable approach to reduce heterosexual transmission of HIV in women that is coitally independent, inexpensive, and enhances the natural protective effects of the vaginal microflora.
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