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Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial.
Lancet Microbe. 2022 Jun; 3(6):e435-e442.LM

Abstract

BACKGROUND

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.

METHODS

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).

FINDINGS

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.

INTERPRETATION

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.

FUNDING

Canadian Institutes of Health Research and the National Institutes of Health National Institute of Allergy and Infectious Diseases.

Authors+Show Affiliations

Department of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: ericm.armstrong@mail.utoronto.ca.Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.Department of Laboratory Medicine, University of California, San Francisco, CA, USA.Ruth M Rothstein CORE Centre, John H Stroger Jr Hospital of Cook County, Chicago, IL, USA.Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.Department of Family Medicine and Public Health, University of California, San Diego, CA, USA.Department of Medicine, Washington University, St Louis, MO, USA.Department of Medicine, University of Toronto, Toronto, ON, Canada.Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.Centre for Global Health Research, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Medicine, University Health Network, Toronto, ON, Canada.Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Medicine, University Health Network, Toronto, ON, Canada.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

35659905

Citation

Armstrong, Eric, et al. "Sustained Effect of LACTIN-V (Lactobacillus Crispatus CTV-05) On Genital Immunology Following Standard Bacterial Vaginosis Treatment: Results From a Randomised, Placebo-controlled Trial." The Lancet. Microbe, vol. 3, no. 6, 2022, pp. e435-e442.
Armstrong E, Hemmerling A, Miller S, et al. Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial. Lancet Microbe. 2022;3(6):e435-e442.
Armstrong, E., Hemmerling, A., Miller, S., Burke, K. E., Newmann, S. J., Morris, S. R., Reno, H., Huibner, S., Kulikova, M., Nagelkerke, N., Coburn, B., Cohen, C. R., & Kaul, R. (2022). Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial. The Lancet. Microbe, 3(6), e435-e442. https://doi.org/10.1016/S2666-5247(22)00043-X
Armstrong E, et al. Sustained Effect of LACTIN-V (Lactobacillus Crispatus CTV-05) On Genital Immunology Following Standard Bacterial Vaginosis Treatment: Results From a Randomised, Placebo-controlled Trial. Lancet Microbe. 2022;3(6):e435-e442. PubMed PMID: 35659905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial. AU - Armstrong,Eric, AU - Hemmerling,Anke, AU - Miller,Steve, AU - Burke,Kerianne E, AU - Newmann,Sara J, AU - Morris,Sheldon R, AU - Reno,Hilary, AU - Huibner,Sanja, AU - Kulikova,Maria, AU - Nagelkerke,Nico, AU - Coburn,Bryan, AU - Cohen,Craig R, AU - Kaul,Rupert, Y1 - 2022/04/21/ PY - 2021/09/17/received PY - 2022/02/11/revised PY - 2022/02/15/accepted PY - 2022/6/6/entrez PY - 2022/6/7/pubmed PY - 2022/6/9/medline SP - e435 EP - e442 JF - The Lancet. Microbe JO - Lancet Microbe VL - 3 IS - 6 N2 - BACKGROUND: 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. METHODS: 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). FINDINGS: 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. INTERPRETATION: 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. FUNDING: Canadian Institutes of Health Research and the National Institutes of Health National Institute of Allergy and Infectious Diseases. SN - 2666-5247 UR - https://www.unboundmedicine.com/medline/citation/35659905/Sustained_effect_of_LACTIN-V_(Lactobacillus_crispatus_CTV-05)_on_genital_immunology_following_standard_bacterial_vaginosis_treatment:_results_from_a_randomised,_placebo-controlled_trial. DB - PRIME DP - Unbound Medicine ER -