Safety, tolerability and colonisation dynamics of a vaginally administered lactobacillus crispatus live biotherapeutic product in pregnancy
File(s)
Author(s)
Bayar, Erna
Type
Thesis
Abstract
The female reproductive tract is colonised by high levels of bacteria and other microbes collectively referred to as the microbiota. Vaginal microbiota dominated by L. crispatus associates with reduced preterm birth (PTB) risk, whilst L. iners dominance and Lactobacillus deplete, high diversity communities associate with increased risk. This thesis investigated whether a live vaginal biotherapeutic, L. crispatus CTV-05 (LACTIN-V) in pregnancy could modulate the microbiota towards a protective state. It was hypothesised that LACTIN-V would be safe, well-tolerated and acceptable, leading to successful colonisation of L. crispatus CTV-05 and reduced local inflammation.
LACTIN-V was administered to 62 women at high-risk of PTB once daily for five days from 14+0 weeks’ gestation and then once weekly for six weeks. Women were assessed at enrolment and at 15+0, 18+0, 20+0, 28+0 and 36+0 weeks gestation, and at delivery. Adverse events and compliance were assessed throughout, and a questionnaire determined acceptability. Vaginal microbiota and L. crispatus CTV-05 colonisation was assessed by metataxonomics, quantitative polymerase chain reaction (qPCR) and culture. Cervicovaginal fluid cytokine concentrations were measured by immunoassays.
LACTIN-V was found to be safe, well tolerated and acceptable during pregnancy (Chapter 3). A persistent shift towards L. crispatus dominance of the vaginal microbiota with L. crispatus CTV-05 colonisation was demonstrated in 65% of women at 28+0 weeks, eight weeks after administration (Chapter 4), alongside reduced cervicovaginal concentrations of IL-1ß, IL-8 and IL-6, particularly in women who transitioned from a high-risk microbiota at baseline.
In conclusion, LACTIN-V use in pregnancy is safe, well tolerated and leads to effective colonisation of L. crispatus in most women, displacing less favourable bacteria and reducing cervicovaginal inflammation. These results support the concept that vaginal administration of a live biotherapeutic containing L. crispatus can modulate the microbiota and immune milieu to a protective state, and so could reduce PTB.
LACTIN-V was administered to 62 women at high-risk of PTB once daily for five days from 14+0 weeks’ gestation and then once weekly for six weeks. Women were assessed at enrolment and at 15+0, 18+0, 20+0, 28+0 and 36+0 weeks gestation, and at delivery. Adverse events and compliance were assessed throughout, and a questionnaire determined acceptability. Vaginal microbiota and L. crispatus CTV-05 colonisation was assessed by metataxonomics, quantitative polymerase chain reaction (qPCR) and culture. Cervicovaginal fluid cytokine concentrations were measured by immunoassays.
LACTIN-V was found to be safe, well tolerated and acceptable during pregnancy (Chapter 3). A persistent shift towards L. crispatus dominance of the vaginal microbiota with L. crispatus CTV-05 colonisation was demonstrated in 65% of women at 28+0 weeks, eight weeks after administration (Chapter 4), alongside reduced cervicovaginal concentrations of IL-1ß, IL-8 and IL-6, particularly in women who transitioned from a high-risk microbiota at baseline.
In conclusion, LACTIN-V use in pregnancy is safe, well tolerated and leads to effective colonisation of L. crispatus in most women, displacing less favourable bacteria and reducing cervicovaginal inflammation. These results support the concept that vaginal administration of a live biotherapeutic containing L. crispatus can modulate the microbiota and immune milieu to a protective state, and so could reduce PTB.
Version
Open Access
Date Issued
2024-04-25
Date Awarded
2025-10-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Bennett, Phillip
MacIntyre, David
Sykes, Lynne
Sponsor
Imperial College London
Publisher Department
Department of Metabolism, Digestion and Reproduction
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)