Meet The Scientist podcast: An interview with Dr. Elana Van Brakel, Medical Director at IAVI, on IAVI’s TB vaccine program

In the latest episode of Meet the Scientist, IAVI’s podcast series, we sat down with Elana Van Brakel, medical director at IAVI in Cape Town, South Africa, to discuss her work at IAVI in support of our TB vaccine program. In this episode, we explore IAVI’s diverse engagement in the development of the MTBVAC TB vaccine candidate and learn about how Elana and IAVI’s TB team are preparing for the Phase 2b clinical trial of MTBVAC in adolescents and adults in sub-Saharan Africa.

Tune in to learn more about Elana’s work and IAVI’s TB vaccine program.

See below for a full transcription of the podcast.

Hello and welcome to the latest episode of IAVI’s Meet Scientist podcast series. I’m Shaun Palmer, a communications and advocacy specialist at IAVI’s Europe hub in Amsterdam and I am pleased to be here today to speak with Elana Van Brakel, Medical Director at IAVI in Cape Town, South Africa, to discuss her work at IAVI in support of our TB vaccine portfolio.

TB vaccine research and development is a core pillar of IAVI’s portfolio, with TB remaining the deadliest infectious disease and much of the world. Now to meet the World Health Organization’s End TB targets by 2030, we urgently need multiple new TB vaccines that are equitably, and affordably accessible around the world. We find ourselves in a historic moment in TB vaccine development this year, following last year’s United Nations High-Level Meeting on TB, which included commitments to develop and roll out new TB vaccines this decade, preferably within five years.

The enthusiasm and anticipation in the field is palpable, with a growing and advancing TB vaccine pipeline and a number of exciting initiatives and events in 2024, including the WHO TB Vaccine Accelerator Council, as well as the 7th Global Forum on TB vaccines, which will take place in Rio de Janeiro in Brazil in October and is co-organised by the Stop TB Partnership Working Group on New TB Vaccines, IAVI, the Ministry of Health in Brazil, and REDE-TB.

So as we can see, this is truly a momentous year for TB vaccine development. And at IAVI, we’re proud to be contributing to this effort. Elana, it’s a pleasure to speak with you today about IAVI’s work in this space and about the role of you and your team in particular. So just to get things started, I was wondering if you could tell us a little about the focus of your work and role here at IAVI.

Thank you, Shaun, and thank you for inviting me. It really is a privilege to be here to talk to you about TB in this exciting time that we’re in, as you’ve already mentioned. And so I’ve just started my third year at IAVI feels like I’ve been part of the IAVI family for a very long time. It really has been an amazing two years. My role is that of medical director in the clinical development team. I’m specifically working on TB projects and what this role involves is basically being the medical lead for a cross-departmental team that is responsible for the design, the implementation, the analysis and the eventual reporting of candidate vaccines for TB. And it also involves design of clinical development plans, you know, the overall development of a vaccine, and eventually also preparing for vaccine access and delivery.

But before we get there, we need to conduct the trial. So there my role is that of oversight of the conduct of the trial and specifically focused on the safety data. Of course, I don’t do this on my own. As I’ve mentioned, I’m part of a cross-departmental team. We have amazing colleagues and also collaborators from across the world that help us do this, this job.

So, I mean, it’s clear that you and your team are engaged in the full breadth of our TB vaccine development and the planning and preparations for our clinical trials. I was wondering if you could just tell us a bit more broadly how IAVI is engaged in the TB vaccine development space.

Sure, so at IAVI we collaborate with partners from around the world, as I’ve mentioned, and our aim is to develop safe and effective and accessible TB vaccines. And together we work across the global hubs with a diverse network of partners to advance the most promising TB vaccine candidates from discovery through clinical trials to post-licensure access. And we also lead policy and advocacy initiatives engaging with international partners to support TB vaccine development and access.

We’re currently partnering with the Spanish biopharmaceutical company Biofabri in the advanced development of the MTBVAC vaccine candidate to see if it prevents TB disease in infants and adolescents and adults. And we’re also partnering with Moderna to assess a series of mRNA candidates, or vaccine constructs, for immunogenicity. So that is basically a measure of the ability and the strength and the type of immune response that a specific vaccine can elicit. And then also, if these mRNA vaccine, constructs can be protective in preclinical studies. So this is still very early on in the development, but we’ll watch this space to see what happens.

So, you know, you can see here we’ve got, you know, some exciting preclinical work, but also some really promising late stage development going on. And you mentioned here the MTBVAC vaccine candidate, which is, as we know, one of the more advanced TB vaccine candidates. But what is unique about MTBVAC as a TB vaccine?

I’m very excited to talk to you about MTBVAC. This really is a very promising vaccine candidate for TB. It was designed by Professor Carlos Martín at the University of Zaragoza, and basically this is the only live attenuated TB vaccine candidate that was derived from an actual mycobacterium tuberculosis sample. So from a human sample and not like not from bovine TB, as is the case for the other live attenuated vaccine that we know, which is called BCG. So basically what happened was they took this Mtb, or Mycobacterium tuberculosis, and deleted some of the genes in the original organism that really makes Mtb a very infective organism. So by deleting these genes, this resulted in a weakened, harmless form of the pathogen that can still elicit an immune response in humans. So it still contains the full range of antigenic targets of the original pathogen. So that means that it has the full range of targets on the pathogen that may be involved in generating an immune response against TB. And that is very exciting to think about.

And the MTBVAC development plan has been running over a number of years. I think about at least 25 years since MTBVAC has been tested in a range of preclinical animal models studies. And all of these demonstrated that compared to BCG, MTBVAC is really as safe as BCG and even more immunogenic and protective. So in humans so far, we’ve, we’ve had four clinical trials completed successfully and these have been conducted in infants and adults. And the first in human trials, that was the very first time the vaccine was given to humans occurred in Switzerland. That was in 2013. And all these trials have been conducted by leveraging the expertise of a global network of partners. So these earlier stage trials have really helped us to define the dose of MTBVAC to be used in adults and in infants and all these trials have also demonstrated really a favorable immunogenicity and safety profile.

Oh, I mean, so wonderful to hear about the exciting history of the development for MTBVAC over what is now, you know, over a quarter century of development. And great to see that it’s finally in late stage development but as a candidate you know how may MTBVAC help control the TB pandemic if it is found to be effective in these late stage clinical trials?

So I’ve mentioned that, you know, that MTBVAC has been tested in infants and it’s also been tested in adults. So they are basically two independent development programs for this vaccine candidate. On the one side, it is being developed as a TB prophylaxis in newborns. And in this development arm, it is already in a very large late stage phase three trial of about 7000 newborns being conducted in South Africa, Senegal and Madagascar. So that is very exciting and also a little bit comforting because it’s already being given to thousands of newborns and no safety issues has been identified. Then, on the other hand, it’s being developed as a TB disease preventive strategy. And this is really targeted at adults and adolescents living in high burden TB countries.
So if MTBVAC work is shown to safely prevent TB disease, it could be critically important in the global efforts to suppress the TB pandemic, given the fact that it’s really easy to use and it only requires a single dose administration. The vaccine platform itself has a relatively low cost to produce, and we also anticipate that it will be widely available to people across the globe. MTBVAC also doesn’t require an adjuvant. So an adjuvant is an ingredient that is added to a vaccine antigen that helps that vaccine to initiate a stronger immune response in the body than when the antigen would have been given by itself. So because MTBVAC does not require an adjuvant, this means that the supply and the price of the vaccine itself is not dependent on an additional commercial partner. So IAVI and our partners are committed to affordable pricing and we are supporting the establishment of a global manufacturing footprint with manufacturing partners already lined up in Europe, India and South America.

Thank you for sharing all of these details about MTBVAC. It’s clear the amount of work going into developing this candidate to make sure that it will be affordably accessible if it is shown to be effective. And for anyone listening, who can hear your dog in the background, I think the excitement is clearly quite apparent in your own household as well. So looking at IAVI’s involvement more specifically, could you tell us a little bit about how IAVI is advancing the development of the MTBVAC candidate?

Sure. So IAVI is more directly involved with the adult and adolescent development program for MTBVAC. IAVI sponsored an earlier phase 1b/2 clinical trial that was conducted in adults and that took place at the South African TB Vaccines Initiative here in South Africa. And a publication on the results of this trial is expected later this year. But what this trial did result in is a dose that was selected for later phased trials, and it also showed that it was compared to BCG in this trial. This phase 2a/1b trial, and it did show that MTBVAC was at least as safe as BCG, which is quite a comfort when you have to think about developing this vaccine further.

So what we are currently doing, we are currently preparing for a phase 2b clinical trial and this is anticipated to start later this year [2024]. And we will investigate whether MTBVAC can prevent disease in adolescents and adults. So essentially this is a what we call a proof of concept study. So this is the first time that we’re going to look at the effectiveness or the efficacy of MTBVAC to be able to prevent TB disease. So we aim to enrol over 4000 people who have latent TB infection. So latent TB infection, just to explain, means that these are people who have been infected with TB. And so you can be infected with Mtb but not be sick or actually have TB disease. So we aim to enroll these people with latent TB infection and all of them will be living in South Africa and several other countries in East Africa. And these are all areas where there is a high TB burden.

We’re not enrolling people living with HIV in this trial. We need to first determine whether the vaccine is safe in people living with HIV. And to that extent, a trial is actually currently running here in South Africa that is specifically looking at the safety and immunogenicity of MTBVAC in people living with HIV. And this is being run by the HIV Vaccine Trials Network. So for our trial, we are enrolling HIV negative participants with latent TB infection in high TB burden countries, and participants will receive a single dose of MTBVAC or a placebo, which is essentially a saltwater injection. And they will then be observed for the occurrence of TB disease over 2 to 3 years. So quite a lengthy trial and requires quite, quite some expertise that I’ll tell you a little bit about later.

I mean, there’s so much work going on in this space. I mean, you mentioned the HVTN trial here in people living with HIV, the earlier work that IAVI has been involved in leading up to this, really critically important phase 2b trial to test the efficacy of MTBVAC in preventing TB disease in adolescents and adults. And before we discuss a little bit further about the work that you and the team in South Africa are doing for MTBVAC development at IAVI, you’ve mentioned how one of the key indications of MTBVAC is to prevent TB disease in adolescents and adults. But why is a TB vaccine for adolescents and adults so important?

So, we have a TB vaccine. It’s been more than a century. It is called BCG, or Bacille Calmette-Guérin vaccine. BCG offers important but incomplete protection against the most severe forms of TB, such as TB meningitis in infants and young children. But unfortunately, it is almost ineffective in adolescents and adults. And adults and adolescents are really the ones most at risk of developing and also spreading TB. In fact, almost 90% of TB cases occur among adolescents and adults. So, we urgently need multiple new TB vaccines that work across all age groups, but particularly among adults and adolescents and that are available in all geographies if we are to meet the WHO 2030 End TB targets and to eliminate TB. I mean, it’s critically important that we have vaccines that work among adolescents and adults to finally end TB, which of course, we hope MTBVAC will be one such candidate, to contribute to this shared mission to end TB as a global health threat.

So, going back to you and your team in Cape Town and elsewhere in South Africa, could you tell the listeners a little bit about how you and your team are contributing specifically to the late-stage development of MTBVAC?

What we’ve done so far since we’ve received the funding for this project, we’ve developed the clinical trial protocols. So, the design and the actual plan on how we’re going to conduct this trial. We initiated and conducted quite a lengthy process for selecting clinical research centers to partner with. So here in this process, it’s a combination of our clinical operations team, which is mostly based here in South Africa and in Cape Town, and also working closely with our epidemiology team, who is sitting in your office, Shaun, in the Netherlands. So, it really is a team effort and it’s not just us here in Cape Town. We really are reliant on contributions from our regulatory people, our epidemiology team, our access to advocacy team like you. So, it really is an amazing team effort.

So just in terms of selecting the or the Clinical Research Centers, we’ve now done that. So, we really, really need to make may make sure that we bring on board centers that have experience in these types of trials or in TB trials in general, that are strong operationally and that are also situated in areas of high TB incidence. So that is why working with our epidemiology team has been crucial in selecting these centers. And a very important part of our planning for any trial is community engagement. And at IAVI we really feel very passionate about engaging the communities where we want to do our trials and really partnering with communities partly to inform them about clinical trials in general. But then also, you know, informing them about the specific trial protocol and that we want to implement, getting their feedback and then just generally training them on clinical trials and making sure that they come on board, and they know what our intention is. And hopefully they, they can share our vision and they can then translate to other members in their community. So that is really an important part of the success of any trial.

Thank you, Elana for such a thorough overview of how you and the team and the global team as well are engaged in this effort. And it’s clear that you know, it’s really the collaboration between a group of individuals bringing all of their experience and expertise to the table to ensure the successful conduct of a late-stage clinical trial, which will be, of course, IAVI’s first late-stage clinical trials once it gets up and running. And I know yourself, you bring a lot of experience from the field to IAVI as well.

And for the final part of the episode today, could you tell us a little bit about your own career working in TB clinical trials to date and what has this work involved and how is this now informing your work at IAVI?

Thank you, Shaun. Yes. So, I’ve completed my master’s of science in Medicine because I wanted to explore this field of clinical research. I was fortunate to be employed by a clinical research center here in Cape Town called TASK. TASK is very well known and a respected research center in the field of TB drug trials over many years. And that is also where I learned about TB and TB clinical research and TB clinical trials, and that has really laid a strong foundation for the work that I’m doing now because working as an investigator on the ground really is proving to be very helpful knowledge to have now where we are planning to conduct a trial. So, it’s also useful when engaging with the staff at the clinical research centers because I’ve been there, I worked there for seven years. And in that time, I was also very fortunate to be an investigator on the actually the very first TB vaccine trial that TASK conducted. That was the other vaccine candidate that is now entering a late-stage efficacy trial and was actually the first vaccine for TB that showed 50% efficacy. So that is the M72/AS01E vaccine.

So, I learned basically what I know about TB vaccine trials I learned there, and it was such a rewarding experience to be part of that and to eventually see when we got the results, and they were positive to really be part of that. And I was also fortunate to be part of the co-writing team that developed the publications that were published in the New England Journal of Medicine. So those two pivotal publications about that, the trial results. And that was an amazing honor and a learning experience for me personally. Now that I’m at IAVI, I’m sort of at the other end of the spectrum. So, approaching this from a sponsor perspective, but definitely my experience as a clinical trial investigator is really proving to be very helpful in my role. And it gives me that insight to know, you know, what would work practically at a site level and at a trial level. So, I’m very happy that I had this journey through task, and I’m very happy to be at IAVI where I am now.

So, as we’ve reached the end of today’s interview and thank you Elana for joining me today and sharing your insights and reflections on your work here at IAVI and earlier in your career and especially on the promising MTBVAC candidate, would you be able to share with us today one thing that you would like the listeners to remember or walk away with from this interview?

Yes, I think maybe, you know, just to have an appreciation for the complexity of Mtb as a pathogen or an organism and how much we still have to learn and understand about the organism. And then just the complexity of designing these trials, planning them, finding the funding. I mean, they’re so costly to conduct and, and, and then also when it gets to the implementation stage, you know, really making sure we partner with the right people, planning it out, planning for all possible situations. I think we’ve already seen earlier in our chat 25 years of clinical pre-clinical development and then starting in 2013 with the first in human trial for MTBVAC you know, just I think an appreciation for this very long journey that we have to go on to get to an eventual new TB vaccine, or at least to a promising TB vaccine candidate.

So that and then on the other side of that, just really, I mean, you’ve mentioned it earlier as well, it’s such an exciting time for the field of TB vaccine development. And for the first time it feels like we’re moving forward, you know, since we’ve had BCG for over 100 years and in all this time, we haven’t been able to get another TB vaccine. You know, we’re now for the first time close due to hopefully having these effective TB vaccines and to have two candidates… You know, like I said, I love talking about MTBVAC, I think it’s such a promising vaccine candidate. So I think just to get that from this podcast is, you know, that excitement and the promise that is as is here at the moment. And you know that what lies ahead might be really groundbreaking change for the field of TB. I would love people do to take away from this conversation.

Thanks again, Elana, for joining us today and for sharing those really motivating words to end on. The year ahead and the field at large, it’s such an exciting moment for TB vaccine development. And it’s a pleasure to, of course, work alongside yourself and the rest of the team on this effort. And I think I speak for all of us in the fact that we’re really looking forward to what’s to come throughout this phase 2b trial and the years ahead for what we hope will be a groundbreaking new tool for trying to address the TB pandemic.

So thanks again for your time and we’ll continue to share updates and news on IAVI’s involvement in MTBVAC development as the program continues to evolve. Thanks again Elana. Lovely speaking with you.

Yeah, really great talking to you today. I enjoyed our time. Thank you very much.

And thanks for listening everyone. Goodbye.