The GIFT Webinar: Women up to Know Good episode 3

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Culturing a cure: new research sparks hope for women’s vaginal health

In the human body, diversity in microbiomes is usually a good thing. For instance, a diverse gut microbiome is linked to better immune functioning and general health and well-being. But when it comes to the vagina, healthy microbiomes are dominated by Lactobacillus bacteria. The absence of beneficial lactobacilli and the presence of many types of anaerobic bacteria are hallmarks of bacterial vaginosis. Affecting around 30% of women worldwide, bacterial vaginosis increases women’s risk for reproductive issues, sexually transmitted diseases and HIV.

In a recent webinar, “Culturing a Cure”, the third in the Women up to Know Good series, a panel of experts discussed innovative research into how to cultivate ‘healthy’, resilient vaginal microbiomes. This research is particularly significant as the current treatment for bacterial vaginosis, a course of antibiotics, has not changed since the 1980s and is not effective in durably eliminating bacterial vaginosis in the long term.

“That treatment is associated with a 60% recurrence in the first six months after treatment,” said physician-scientist Caroline Mitchell of the Massachusetts General Hospital in Boston, USA. “Given the tools we have these days in science, [this] is really unacceptable. We should be doing better for women.”

Fellow speaker Sarah Lebeer, a microbiologist at the University of Antwerp, noted that while scientists understand the conditions associated with bacterial vaginosis, they don’t yet have a clear understanding of how to promote a healthy vaginal microbiome.

For instance, after antibiotic treatment that reduces bacterial vaginosis-associated bacteria, the remaining vaginal microbiome mainly comprises Lactobacillus iners. “Unfortunately, iners is not one of our more beneficial lactobacilli…,” Mitchell explained. “What we would rather have is a vaginal microbiome dominated by Lactobacillus crispatus, which we think of as the most optimal Lactobacillus, no matter where you live in the world.”

1. crispatus, however, can sometimes be a reluctant coloniser. Research over the past decade suggests that post-treatment implants of a single L. crispatus strain after antibiotics administration are largely insufficient to drive a durable, positive shift in the microbiome towards optimal. Six months after use of these single strain L. crispatus products, recurrence of bacterial vaginosis is still 30-60% – which is “way too high”, Mitchell said.

She and CAPRISA’s Dr Disebo Potloane shared early insights from two innovative studies seeking to shift the microbiome durably in women with recurring bacterial vaginosis. At the heart of these studies is the idea that L. crispatus, like people, needs community to thrive.

Creating community

The Live Biotherapeutic Randomised Trial (VIBRANT) aims to find out whether L. crispatus is better at colonising the vagina when combined with other kinds of Lactobacillius species. Across two study sites, the VIBRANT team is assessing the safety and efficacy of a vaginally inserted tablet containing multiple live L. crispatus strains donated by women with stable optimal vaginal microbiomes.

In the USA, Mitchell leads the study arm at the Massachusetts General Hospital. In the rural community of Vulindlela in the Kwa-Zulu Natal Midlands, South Africa, Potloane leads the other study arm at CAPRISA. Here, women face an exceptionally high risk for HIV acquisition: two-thirds of those aged 35-39 are living with HIV.

Finding sustainable solutions to bacterial vaginosis in this and other high-risk communities is an essential component of future HIV prevention strategies.

From women in the USA and South Africa, Mitchell, Potloane, and their colleagues isolated 15 strains of L. crispatus from women with L. crispatus-dominant vaginal microbiomes, as part of a major global collaboration called Vaginal Microbiome Research Consortium (VMRC). Of these 15 strains, they also identified 6 that cover a wide range of genetic variations found in the L. crispatus species. Together, the consortium produced two innovative prototype pills containing live bacteria: a 15-strain consortium and a 6-strain consortium.

At each study site, fifty to sixty participants with bacterial vaginosis will be randomised into different study arms that test both consortiums against placebos. After five weeks, the team will test for shifts in the microbiomes and follow up again at 12 weeks. At the end of that period, they’ll better understand the safety of the treatment and the ability of the novel multistrain L. crispatus communities to colonise the vaginal microbiome. The findings will also shed light on optimal dosing frequency and duration for future studies.

“Our goal is to reduce adverse reproductive health outcomes and also reduce HIV risk in women. This first in-human study is among the first steps along that road,” Potloane said. “Our long-term goal for the project is to find an intervention that can prevent incident bacterial vaginosis in women, in people at risk, and hopefully we would be able to do that without antibiotics.”

It takes a village

The Vaginal Microbiome Transplant study (MOTIF), led by Mitchell, takes a broader approach to providing transplanted L. crispatus with a social support network. “The idea behind vaginal microbiome transplant is just, let’s put the whole good community in, and that will help us figure out what is necessary,” Mitchell said. Vagina microbiome transplants have been tried before with encouraging results, but only in small studies.

MOTIF is the first randomised vagina microbiome transplant trial for recurring bacterial vaginosis. Mitchell emphasised the importance of safety in the trial, with donors screened extensively for STIs or other infections. Over 45 days, participants provide donations using a disposable menstrual cup.

Although the study is ongoing, the pilot safety trial of the first eight recipients (with transplants from one donor) hints at encouraging results. One month after receiving either a transplant or a placebo, Mitchell and her team assessed the microbiome composition. Of the four individuals who received placebos, one achieved a microbiome with some L. crispatus, “although It never exceeded 50%”, Mitchell said. In the treatment arm, the microbiomes of 3 of 4 women shifted to L. crispatus-dominant. Six months after treatment, 2 of 4 transplant participants had greater than 50% Lactobacillus crispatus.

“Fifty per cent may not sound like a lot, but all of these [women] have highly recurrent bacterial vaginosis, very similar to the Israel case series [study], where several of them said, ‘You know, I just don’t go to the doctor anymore because nothing works. I’ve given up…'” Mitchell said. “And so, to us, 50% is incredibly, incredibly exciting.”

The trial will proceed with a larger cohort of participants and more donors. Mitchell’s team is looking to answer important questions such as whether it’s beneficial to match the characteristics of donors and recipients, and how many doses will be needed.

Global sisterhood projects

Meanwhile, Serah Lebeer is among the scientists helping to improve our knowledge of ‘healthy’ microbiomes. “The field is very much dominated by research on problems and infections, problems such as bacterial vaginosis,” she said. “But if you want to better understand these conditions and…develop better treatment options, you also need to better understand the reference [health] and the comparison [bacterial vaginosis]. For that, you need interaction with citizens.”

So, she and her colleagues launched the Isala Sisterhood, a citizen science project to create a large biobank of beneficial vaginal bacteria to enable innovative microbiome therapies. By working with women all over Belgium, the project aims to map the microbiomes of healthy women outside of hospital settings.

Despite their ambitious targets, within ten days of launching the call for volunteers in Belgium, Lebeer’s team had reached their enrollment goal of 200 women. “For us, it’s an example that women’s health matters to all women – they all want to know about the vaginal microbiome,” she said. Early findings from the Isala Sisterhood project have recently been published, revealing new associations between vaginal microbiome composition and lifestyle and diet.

Now involving 6000 women, the Sisterhood project has spawned many new sisterhood projects in other countries and new research avenues. In each country, the study is named after an influential female role model in health or science. In South Africa, the team behind the novel Genital Inflammation Test (GIFT) is working with Isala to establish the Mary Malahlela project, named after the country’s first black woman doctor. These locally led projects emphasise collaborating with women to improve our understanding of vaginal health. GIFT is another international, women-led project working to improve women’s vaginal health by making bacterial vaginosis screening a reality in low- and middle-income countries. 

By promoting healthy vaginal microbiomes, these researchers aim to safeguard not only women’s reproductive health, but also their general wellbeing– and that of their partners and children. “For me, the vaginal microbiome is the most important microbiome,” Lebeer said.

Written by Andrea Teagle for Jive Media Africa. Jive Media Africa is the communications partner of the GIFT project.