细菌性阴道病可能通过引发生殖器炎症和上皮屏障破坏而增加HIV风险。而阴道卷曲乳杆菌与免疫静止和HIV保护有关。我们研究了含有LcrispatusCTV-05(LACTIN-V)的活生物治疗剂对生殖器免疫学和关键阴道细菌的影响。
这项子研究纳入了18-45岁的女性,她们参与了随机研究,安慰剂对照,LACTIN-V减少细菌性阴道病复发的2b期试验,在美国的四所大学和医院进行。性传播感染结果阴性的女性,怀孕,和尿路感染提供5天疗程的阴道甲硝唑0·75%凝胶。符合细菌性阴道病的四个临床Amsel标准中的至少三个,并且革兰氏染色的Nugent评分为4-10的人符合条件。LACTIN-V试验的参与者被随机分配(2:1)接受LACTIN-V或安慰剂,在第一周内每天阴道一次,持续5天,然后每周两次,持续10周。在入组后4、8、12和24周进行随访。通过多重ELISA和定量PCR测定可溶性免疫因子和细菌分类群的绝对丰度。主要结果为24周时阴道IL-1α和可溶性E-cadherin水平(即,治疗停止后13周)。
在2020年2月21日至2021年3月18日之间,我们对随机选择的66名高度粘附参与者的子集的生殖器免疫参数和阴道微生物群进行了表征。没有排除标准,在较大的LACTIN-V临床试验(n=288)中,参加了所有研究随访的人(n=166)。32名(48%)参与者接受LACTIN-V,34名(52%)接受安慰剂。LACTIN-V治疗与较低浓度的促炎细胞因子IL-1α(β系数0·310,SE0·149;p=0·042)和可溶性E-cadherin(0·429,0·199;p=0·035)显着相关,上皮屏障破坏的生物标志物。
标准细菌性阴道病治疗后阴道给予LACTIN-V导致生殖器炎症的持续减少和上皮完整性的生物标志物。Lactin-V降低HIV易感性的潜力值得进一步研究。
加拿大卫生研究院和国立卫生研究院国家过敏和传染病研究所。
Bacterial vaginosis might increase HIV risk by eliciting genital inflammation and epithelial barrier disruption, whereas vaginal Lactobacillus crispatus is associated with immune quiescence and HIV protection. We investigated the effect of a live biotherapeutic containing L crispatus CTV-05 (LACTIN-V) on genital immunology and key vaginal bacteria.
This substudy included women aged 18-45 years who participated in the randomised, placebo-controlled, phase 2b
trial of LACTIN-V to reduce bacterial vaginosis recurrence, conducted at four universities and hospitals in the USA. Women with negative results for sexually transmitted infection, pregnancy, and urinary tract infection were provided a 5-day course of vaginal metronidazole 0·75% gel. Those who met at least three of four clinical Amsel criteria for bacterial vaginosis and had a Nugent score of 4-10 from Gram staining were eligible. Participants in the LACTIN-V
trial were randomly assigned (2:1) to receive either LACTIN-V or placebo, applied vaginally once per day for 5 days during the first week and then twice per week for 10 more weeks. Follow-up visits occurred 4, 8, 12, and 24 weeks after enrolment. Soluble immune factors and the absolute abundance of bacterial taxa were assayed by mutliplex ELISA and quantitative PCR. The primary outcomes were vaginal levels of IL-1α and soluble E-cadherin at 24 weeks (ie, 13 weeks after treatment cessation).
Between Feb 21, 2020 and March 18, 2021, we characterised genital immune parameters and the vaginal microbiota in a subset of 66 highly adherent participants who were randomly selected, with no exclusion criteria, from those who had attended all
study follow-up visits (n=166) in the larger LACTIN-V clinical
trial (n=288). 32 (48%) participants received LACTIN-V and 34 (52%) received placebo. LACTIN-V treatment was significantly associated with lower concentrations of the proinflammatory cytokine IL-1α (β coefficient 0·310, SE 0·149; p=0·042) and soluble E-cadherin (0·429, 0·199; p=0·035), a biomarker of epithelial barrier disruption.
Vaginal administration of LACTIN-V following standard bacterial vaginosis therapy resulted in a sustained reduction in genital inflammation and a biomarker of epithelial integrity. The potential of LACTIN-V to reduce HIV susceptibility merits further investigation.
Canadian Institutes of Health Research and the National Institutes of Health National Institute of Allergy and Infectious Diseases.