The Root Of The Science Podcast
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The Root Of The Science Podcast
EP 155: Prof Lee Fairlie, M72 Vaccine Trial in South Africa: A New Era in TB Treatment
Tuberculosis remains one of the deadliest infectious diseases globally, claiming approximately 3,400 lives daily.
On this World TB Day episode, We speak with Professor Leigh Fairley, Director of Maternal and Child Health at Wits RHI and Associate Professor at the University of Witwatersrand, about groundbreaking research that could transform TB prevention.
As a key figure in the M72 trial, she discusses the M72 trial, its significance in the fight against TB and the potential impact the vaccine will have in South Africa.
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Just to make the distinction between TB infection and TB disease. So only about 10% of people who get infected with TB will actually go on to develop disease. But we know that actually many you know, probably over 50%, probably even higher of South Africans might actually have had previous TB infection. Globally, it's probably about one in four people have got evidence of TB infection previously. But, as I say, only a small proportion of those people will go on to develop disease. And and that's what they found in the the sort of first phase two study and that's what kind of raised all the excitement and and then led on to the M72 study. What they basically found is that in people who had evidence of previous TB infection, tb disease or pulmonary TB could be prevented in about 50% of those people.
Speaker 2:Hello everyone and welcome to another episode of the Root of the Suns podcast with your girl, anne. If you are new here, welcome to the show and if you are regular, thank you so much for tuning in. A reminder that if you're watching on YouTube, please remember to click the subscribe button and share this episode wide so that more people can have access to this wonderful information that we are sharing, so that more people can have access to this wonderful information that we are sharing. So, if you're listening to this, today is the 24th of March, which is World TB Day, and that's what our episode will be about. This episode will explore South Africa's TB landscape and the recent breakthroughs in treatment and prevention, and also some of the transformative impact of innovation and technology in fighting against TB.
Speaker 2:I'm so happy to be joined by Professor Leigh Fairley. She is the Director of Maternal and Child Health at WITS RHI and also an Associate Professor at the University of Witswatersrand in South Africa. Her work focuses on preventing and treating HIV, tb and other infectious diseases in children, adolescents and mothers, especially those affected by HIV. In our discussion today, we'll highlight the M72 trial, which is a TB vaccine trial. We'll discuss its significance in the fight against TB and the potential impact that the vaccine will have in a country battling with high TB burden.
Speaker 2:Professor Lee is a leading expert in public health and a key figure in this trial, and will discuss the vaccine's development, its potential impact and the challenges of bringing it to fruition, the importance of community engagement in this process and the role of research institutions that are driving progress towards a TB-free future. Lastly, we'll also touch on the broader TB landscape in South Africa and highlight the need for continued investment and collaboration to end this persistent public health challenge. Tune in for all of this and so much more. Let's go. Hello, professor Lee, welcome to the show.
Speaker 1:Thank you so much, Anne, and thanks for the invitation to join.
Speaker 2:It's such a pleasure. So, Professor Lee, to just get straight into it, can you kindly just introduce yourself and explain your role in this field of TB and health research?
Speaker 1:Sure, so my name is Leigh Fairley. I am a pediatrician by training. I'm the Director of Maternal and Child Health at FitzRHI, I'm an associate professor within the University of the Wattwatersrand and I lead the Shandakani Research Centre. So essentially we conduct mainly clinical trials and implementation science research at the unit. Research at the unit we traditionally have mainly included pediatric and maternal populations as well as obviously adolescents included in the pediatric populations. But then in COVID really got very involved in more kind of adult populations've got very involved with the COVID vaccine research work and then our portfolio of TB vaccine work and other TB prevention work has also sort of grown in the last few years. So we've been involved in the BCG REVAX study which was revaccinating adolescent participants, then the TB MISA study which really looked at M72 in people living with HIV who had well-controlled HIV disease and now were involved in the M72 or Community B study and I'm the co-national PI with um professor villain william hannah corn fantastic um.
Speaker 2:Thank you so much for painting that picture um for us and to making us understand your role in this. I'll just like to ask you on a personal front. You did mention you're a pediatrician by training, so what made you um like sort of navigate and go into clinical research instead of, you know, handling babies in the hospitals, for example?
Speaker 1:Yeah, so I actually, when I left, when I completed my training, I actually joined a pediatric HIV clinic at Krishani Baragwanath Hospital and so actually pediatric HIV was really and still is actually my passion. So you know, that's where I kind of started out, I guess, in my pediatric career. But then, you know, because we were donor funded that particular organization and because actually, because of of um, effective prevention, or what was at that stage called prevention of mother-to-child transmission and now is called vertical um transmission prevention, um, you know, we know that increasingly there are less and less babies becoming infected with HIV. A lot of adolescents are still aging into having their, you know, having HIV and growing old with it. But because the treatment for, you know, for children and adolescents and actually pregnant populations, has really transformed over the last few years, it really has meant that there are now very few issues with pediatric HIV treatment or adolescent treatment or maternal for that matter.
Speaker 1:So we realized that we kind of needed to pivot. So we actually moved then to inner city, johannesburg, our unit, and joined an organization called VITS RHI, and so then we started actually doing more maternal work, so maternal vertical transmission work, so looking at optimized HIV treatment for women to prevent onward transmission but also for their own health, and then also looked at HIV prevention in maternal populations and then got more involved in the vaccine field. So we've done a number of different maternal vaccine studies and then, as I sort of briefly mentioned, when COVID came along we were kind of well placed to to do quite a lot of the COVID vaccine studies and then always had a passion as well for for TB, um, and, and so you know it was also then we we moved on to to do a number of of um, adolescent and adult TB vaccine studies.
Speaker 2:Oh, lovely, lovely, what a beautiful journey of you pivoting and finding your place in this field. And, as we're speaking about TB, because this episode is coming out on World TB Day, when I was preparing for this, I read some of the stats, and one of them that really struck me was the one from the World Health Organization where they estimated that 10.8 million people fell ill with TB, for example, in 2023, and 1.25 million of them actually died, which is essentially about 3,400 people a day. This is a very scary statistic and really paints a grim picture. So, for our viewers, who might not really understand the scale of some of the work that you're doing and why you're doing, could you maybe please help us understand where this vaccine, the M72 vaccine, comes in and its significance against this backdrop that I've just painted?
Speaker 1:Yeah, so you know, although there's very effective TB prevention strategies in terms of oral medications, obviously that then relies on people having to take daily medications. I mean, I think we all know how easy it is to kind of forget, or someone feels well so, or you know they may have had a TB contact, but then that person gets well, and so you know so that ongoing pressure might lift or it just might be too difficult for them to be able to take oral medications. And so, even though there are good oral prevention strategies, and so even though there are good oral prevention strategies, a vaccine really would be a game changer. And currently BCG vaccine is given to small babies, so not in every country, but certainly in the countries where the M72 study is conducted, which are high burden TB countries. So that's given to babies essentially very shortly after birth, and that does protect babies, for we think at least the first five years of their lives protects them against severe disease, certainly. But then after that any sort of protection or immunity starts to wane. And so what we really need is to actually prevent TB disease in people who are actually going to be the ones who spread it, which is mainly adolescents and adults. And so the M72 vaccine is really targeted. Well, at this stage, I mean the you know, I'm sure you're aware of the age group included in the study, which is 16 to 44 years, recognizing that that is really the you know where the kind of burden of disease is, and then onward transmission and obviously at later stages other age groups may be added, but that is certainly the, the, the target um group for this particular study, um, and and the.
Speaker 1:The vaccine was developed about five years. Well, sorry, the first data came out about five years ago, where the study was conducted, actually looking at vaccine efficacy in HIV negative people who had evidence of having had previous TB infections, so they were what we call IGRA positive. They had a blood test which showed that they had been infected with TB. So those were very encouraging results and that really sets the basis for the M72 study. The previous study was a bit smaller, so I think there were about 2,000 people enrolled and this study actually enrolled 20,000 people, so really hoping to replicate the results that were seen previously, but then in a bigger group of people and some geographic diversity as well. So I think, as you're probably aware, the study's been conducted in five countries. So South Africa, malawi, zambia and Kenya, and then Indonesia. The majority of participants will be enrolled in South Africa, so about 60% 18,000 people have got evidence of previous TB infection, so they've got IGRA positivity. 1,000 are people living with HIV and then 1,000 are people who don't have evidence of previous TB infection.
Speaker 2:Oh, so it's a really broad net of people that you're testing. I mean who are? Going through this trial. Prof, I actually want to backtrack for a moment. You mentioned something that I found quite interesting the distinction between TB infection and tb disease. Um, could you maybe further alliterate for some of us, because so when you have tb you can get cured like the flu. And then what's the difference between the disease side of it, so that we can really have a proper understanding there?
Speaker 1:um, so so many. You know many South Africans, for example. I mean, I'm using South Africa probably as a example country, because you know we I mean I guess that's our environment and we know that the TB really remains um a huge problem here.
Speaker 1:so many South Africans will have been infected with TB but what happens is that their body and their immune system are able to actually control that infection. So they then get the infection basically gets controlled and sometimes on x-ray you can see a small little sort of calcified lesion in the lungs. Can can show that they that that has you know that they have managed to control it. They've formed um a little, uh, what we call um gone focus and then that that eventually might calcify um and that just shows that somebody's actually previously been infected, but infected but they've managed to control the infection. But I mean, obviously we can't do that on everybody and not everyone will present in the same way. But what we can also do is we can do a blood test so similar to it's called an interferon gamma release assay and it's similar to an ELISA test, for example, that we would do for HIV. So basically that picks up um antibodies or a response to TB in in the bloodstream and so we can see from that whether somebody has actually been previously infected with TB or not.
Speaker 1:In the older days we used to do a TB skin test. So many kids used to actually have that done as part of clinic care when we were looking to see if children had been infected with TB, but that's not done as commonly anymore. So basically, if someone is able to control the infection, they can reactivate it at a stage. So sometimes people can reactivate, you know, if they become ill for any other reason or immunosuppressed for any other reason. So obviously you know someone newly diagnosed with HIV, if they've got a very low CD4 count, for example, that might be a risk, but mostly that never reactivates and those people remain dormant.
Speaker 1:But obviously what you're trying to prevent is the people who are at risk for actually then going on to develop TB disease. That's the step that we want to prevent, fascinating, and that's what is targeted by the actual therapeutic interventions. But then also that's the way that a vaccine would work. So basically, the the way a vaccine works is that it's obviously trying to trick the body into thinking it's being infected with TB mountain immune response and then that's how, how the the vaccine basically protects against, sometimes against infection. But I mean obviously with this particular study, the main thing we're really trying to do is to prevent disease, because many of these people have been infected. Well, the majority of participants have been infected with TB previously.
Speaker 2:This is so fascinating. I'm learning so much and I'm sure even our listeners are. So you mentioned for us, you gave us, some of the key phases of the trial. You told us where it's currently happening, the amount of people who are involved. So are there some major findings that you were able to tell us that are happening in this trial so far?
Speaker 1:So we don't have any results of the study yet and we can't really discuss any of the study data yet. I think just to say that you know, majority of participants have now been enrolled and I think we're hoping that towards the middle of the year at the latest that all of the participants will be enrolled and and then essentially the study follows. So just to clarify, it's two vaccines that people get, so it's a double-blinded randomized study. So basically meaning that the investigator or the site staff only the pharmacists know what someone's been randomized to, but everybody else does not know what the person has been randomized to, and so half the participants get the M72 vaccine, half get a placebo and then they obviously have regular study visits throughout. They obviously have regular study visits throughout and we anticipate that the study will continue for at least four years.
Speaker 1:The endpoints of the study are if people develop TB disease which is confirmed microbiologically on this study. So basically, obviously we hope that people do not get TB, but we know that in our natural environment people will be infected and potentially diseased with TB. 10 participants have got confirmed TB disease. Then we'll be able to look at the different arms, so the placebo and the vaccine arm and hopefully what we're going to see is that the people in the vaccine arm are much less likely to progress to become diseased with with tb than the placebo arm yeah, no, that's so fascinating.
Speaker 2:Um, I'm just thinking on the chat of vaccine hesitancy. That was a huge thing. That came obviously after covid and it was really brought into the forefront. So, uh, with that being said, are people willing and are interested? We know that South Africa has a high burden of TB. When the results come, are people willing and interested to get vaccinated with this vaccine? Because a lot of people are doing a lot of work behind the scenes. So how's the perception of people with some of the communities that you work in?
Speaker 1:Yeah. So I mean we have managed, and certainly the trial has managed, to recruit the participants. You know I mean there has not been a problem with being able to find people who are interested in being part of the study. But certainly you know you raise a valuable point. But certainly you know you raise a valuable point, I think once you know obviously there's a whole sort of process but once the vaccine is shown to be efficacious, you know, then has to be registered and then the plans need to be implemented around actually rolling the vaccine out and that's probably kind of five years down the line. And that's probably kind of five years down the line.
Speaker 1:But I think in the meantime there is actually a lot of work ongoing looking at all of these different aspects. So you know people are looking at some of the questions around vaccine hesitancy because certainly that was a major issue over COVID no-transcript. But I think where we have to work is really with our communities. We have to work with our community advisory boards. We really have to understand what is driving the vaccine hesitancy. You know what are people concerned about, about receiving the vaccines, and you know what we may even and often might find is that people who are sort of almost in the highest burden environments might be the people who have the most vaccine hesitancy and obviously you know those are people that we really need to work carefully with.
Speaker 1:I think people don't always understand TB very well, so a lot of sort of community and education needs to come in around explaining what TB is, explaining, you know, why we need to prevent it and I think a lot of South Africans have been touched by TB in terms of, you know, family members or friends or whatever.
Speaker 1:So, I think, just heightening people's understanding of what the issue is and why it's so important for us to prevent it. I think it really is critical work and, you know, I think that's the kind of work that is and has to continue to be done while you know, while the clinical trials are ongoing, because you know you can't just have a product and then no one wants to take it. You know, and you have to think carefully even around you know, your kind of higher risk or higher burden communities because again, issues of stigma might come in. You know people might feel stigmatized if they feel that they're being targeted for a vaccine, etc. So all of these things actually do need to be mapped out even before you know. We know that we've got a product actually do need to be mapped out even before you know we know that we've got a product.
Speaker 2:That's so true, I think. The issues of stigma, especially because with TB there's a high correlation with HIV. So how do you then work? What are some of the strategies, for example, that you do in working with communities that may show some hesitancy around vaccine acceptance?
Speaker 1:Yeah, and you know it's not only HIV, I think, because TB is so caught up in socioeconomics and inequity and malnutrition, for example, and we know that all of those are still sort of pertinent issues in in South Africa, um, and and so we need to work with with all of those different aspects. I mean, I think that it's it's always important to understand where the where the hesitancy and and where the concerns are around a particular vaccine or around a particular product and so a lot of the sort of strategies around that are engaging with the CABs. They are often, you know, much more sort of plugged into community perceptions, you know, than we might be as researchers. And also, obviously, you know, when we're chatting to a participant there may be some bias. You know they may not want to be as honest with us as they may want to be with other people who they might feel more comfortable with, you know. So I think it's really trying to tap into the community, tap into the community voices and really understand where people's hesitancy is. Sometimes people seem, you know, some of what we discovered when, you know, when we were actually recruiting for the study is that sometimes people still perceive HIV to be a higher risk problem than TB. So perhaps also thinking about strategies around kind of TB and HIV co-testing when we do these sort of tests and I think there are also a number of projects that are ongoing looking at that. So you know, people might be more comfortable to engage with something if they feel that we're ticking more boxes than just.
Speaker 1:Okay, here here's a tb vaccine, you know, um, I think, also just generally understanding where, where people's lack of of knowledge around um, tb and the importance of a vaccine is. I think that's very important. And then thinking about co-creating materials with community, because you, you know, again, this sort of top-down oh here are materials approach doesn't always work because you might not be getting to what is actually bothering the person about understanding TB, for example. And then I think a lot of work also, you know, needs to be done with healthcare workers. I think that, you know, one of the things we also saw with COVID particularly was that healthcare workers felt uncomfortable about vaccinating certain populations with COVID vaccines.
Speaker 1:So, for example, pregnant women or postpartum women, people were actually quite reluctant to do that but that was actually the highest risk group, you know, for morbidity and mortality, especially pregnant women who became infected with COVID. So I think, working also with the healthcare workers, to fully understand you, you know the safety data where we're thinking that the vaccines are best placed and and you know the optimal population to to actually vaccinate, I think if the healthcare workers are on board with that it's, you know, makes a huge difference because obviously, as a healthcare worker, if someone's not advocating for for vaccines, you know you really you're going to have a major problem with actually kind of rolling them out yeah, and I think, even with healthcare workers, um, those are the people who, um the patients trust you know.
Speaker 2:So if they actually, um, if they are supporting this, then a patient is more likely to take it on. And just, we've touched on the idea of healthcare workers. I can imagine, in a project like this, it involves various actors and you know a lot of stakeholders at various different levels, such as healthcare workers, researchers like yourself and, I'm sure, government and community members. So how do we, how do you manage that type of collaboration in a very big trial like this, especially because you're also working in different countries? Um, how does that happen?
Speaker 1:yeah. So I think that certainly currently they they've been behind the scenes discussions with various stakeholders. I mean we obviously have regular team meetings but as yet there haven't been sort of big stakeholder meetings and so certainly I think that is something that would be planned for the future and there are a number of implementation science projects on the go that are actually looking at those various aspects. So I think that is it is really a work in progress From the site point of view. You know we are engaging with our direct stakeholders and our CAB, et cetera stakeholders and our cab, et cetera. But you know, certainly as the study progresses there'll need to be much wider stakeholder engagement, as you say. You know, with all the various different role players and obviously largely kind of guided by departments of health and the ministry. You know, I think that they would obviously be the key players in any decisions about vaccine rollout.
Speaker 2:Precisely, and I think obviously, once it's reached that point, it does need that national level. You know implementation and working together at that point. So I just wanted to, maybe as we're starting to wrap up this really insightful conversation that we've had, I wanted to ask you can you share some of your insights and maybe some of the implications with the ongoing trial? That like what is your hope for the future? Let me put it that way With this trial? That it's still in the infancy, but you know what is your hope in this?
Speaker 1:Yeah, I mean, my hope really is that we will be able to replicate those results from the previous study and show that the M72 vaccine is efficacious in being able to prevent TB disease in, you know, a high proportion of people and really you know that we'll be able to then roll it out to the broader South African and sort of global population. I mean, I think it really is. It would be a game changer in terms of TB prevention and all the burden that TB actually brings. It's not just a health burden, it's a tremendous financial burden to families. It keeps children out of school, adults out of work, et cetera, and so all of those kind of long-term implications. So hopefully the vaccine works, we'll really be able to make a huge impact in terms of TB prevention.
Speaker 2:That's amazing, and I like what you said about the idea that it's got such cross-border implications. It's not just a health issue, it's a financial issue. You know it involves so many things at the end of the day, and I think that's why work like the ones that you're doing is so important. So one last question this is really difficult work and I'm sure it gets really hard, but what keeps you motivated to be able to still do what you do all these years that you've been involved in this type of work?
Speaker 1:Well, I mean, I think I'm lucky to have a great team, so I think the team always kind of keeps you on your toes and keeps you motivated and kind of you know that they're also a number of other people um depending on you.
Speaker 1:Um, I mean, I think the nature of the work, I think it's it's quite exciting to be involved in these kind of studies that that really, you know would have a global impact and and can make a big difference in people's lives. You know, and I'm lucky enough to still see patients and do the kind of one-on-one interactions, but it is also nice to be able to do that on a kind of higher level, you know kind of broader public health level. Yeah, I mean, I guess I'm genuinely a fairly positive and optimistic person. I mean I have good support from my family, which I think also helps, and friends, and so I guess you know it's just kind of some sometimes it's really just putting one foot in front of the other, but on the whole, yeah, I mean I think that the sort of vision and, you know, all the people around me who help motivate me, really you know that's what kind of pushes me forward.
Speaker 2:Oh beautiful. I love that. I think as much as you are, you need to have a village that you know you are on the shoulders of, and it's beautiful that you share that. Prof, it's been such a wonderful conversation talking to you today. Like I said already, I learned so much, and I'm sure many people have, and I can't wait maybe in years to come, when the trial has got into a place where we can have more in-depth conversations, we can come back and sort of see how far we are. So thank you so much for your time, especially today.
Speaker 1:Great Thanks. So much Thanks for the opportunity You're so welcome.
Speaker 2:And, to everybody else who's here, thank you for tuning into another episode of the Roots of the Sun podcast with your girl and with Ani. Until next time, goodbye.
