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经阴道传播的 HIV 预防疫苗:一种新型重组乳酸杆菌的活体应用。

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

机构信息

Gene Structure and Regulation Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

Mucosal Immunol. 2011 Nov;4(6):648-57. doi: 10.1038/mi.2011.30. Epub 2011 Jul 6.

Abstract

Most human immunodeficiency virus (HIV) transmissions in women occur through the cervicovaginal mucosa, which is coated by a bacterial biofilm including Lactobacillus. This commensal bacterium has a role in maintaining a healthy mucosa and can be genetically engineered to produce antiviral peptides. Here, we report a 63% reduction in transmission of a chimeric simian/HIV (SHIV(SF162P3)) 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 sixfold. Colonization and prolonged antiviral 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, which is coitally independent, inexpensive, and enhances the natural protective effects of the vaginal microflora.

摘要

大多数女性体内的人类免疫缺陷病毒(HIV)传播是通过宫颈阴道黏膜进行的,该黏膜被包括乳杆菌在内的细菌生物膜所覆盖。这种共生细菌在维持健康的黏膜方面发挥着作用,并且可以通过基因工程来产生抗病毒肽。在这里,我们报告称,经过反复阴道挑战,用表达 HIV-1 进入抑制剂氰基乳杆菌的乳杆菌詹森处理的猕猴,其感染嵌合猴免疫缺陷病毒(SHIV(SF162P3))的传播减少了 63%。此外,突破感染的定殖猕猴的峰值病毒载量降低了六倍。通过基因工程改造的乳杆菌的定殖和持续抗病毒蛋白分泌并没有导致任何促炎标志物的增加。这些发现为一种易于获得且持久的方法奠定了基础,这种方法可以减少女性中异性恋传播的 HIV,其不依赖于性行为,成本低廉,并增强了阴道微生物群的天然保护作用。

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