Professor Glenda Gray, former president and CEO of the South African Medical Research Council, is the Principal Investigator of the BRILLIANT Consortium, a USAID-funded cooperative agreement dedicated to accelerating HIV vaccine discovery and development in Africa. She was one of TIME Magazine’s most 100 influential people in the world, and she has also been listed by Forbes as one of Africa’s 50 most powerful women. Professor Gray co-founded and directed the renowned Perinatal HIV Research Unit at the Chris Hani Baragwanath Hospital and is the Co-PI of the NIH-funded HIV Vaccine Trials Network (HVTN).
We sat down with Professor Gray to ask her some questions about the BRILLIANT Consortium.
The BRILLIANT Consortium is a significant initiative led by African scientists. Can you elaborate on why it’s crucial for African scientists to take the lead in HIV vaccine research and development for Africa?
African scientists are ready to take the lead in developing an effective HIV vaccine. Many of our scientists have been involved in understanding the viral dynamics and the diversity of HIV in Africa. We also have been studying breakthrough infections that occur in clinical trials and understand the pressure that previous vaccines have put on viral evolution, and also how the virus evolves over time. We have the virologists and immunologists in Africa that are ready to take these findings and design HIV vaccines that are suited for the African continent.
At a global level, there are many scientists involved in HIV vaccine development, but their initiatives may mostly be involved in finding solutions for clades of HIV or subtypes of HIV that circulate on their continent. For instance, in Southern Africa, clade C or subtype C HIV predominates, whereas in East Africa there’s a combination of clade A, C and D and in West Africa, there are also recombinant forms of HIV and subtype G. It’s important for us to look at the viral evolution on the African continent and design immunogens that will target the circulating subtypes that occur in Africa.
What are the unique strengths and perspectives that African researchers bring to this challenge?
The unique strengths and perspectives is a deep understanding of the natural history and epidemiology of HIV on the continent, not only from a molecular and virological point of view, but also from a clinical point of view. We have also developed the necessary laboratory and clinical infrastructure to respond to being part of the innovation to find an HIV vaccine.
The third point about being involved in HIV vaccine discovery is to invest in HIV vaccine platform and immunogen R&D. Although a lot of research has happened on the African continent, there has been very little development. By that I mean development of vaccine platforms and vaccine manufacturing capability to make an HIV vaccine, as well as the preclinical steps that are required.
This grant is the first of its kind that empowers scientists, and in this case African scientists, to take a concept from discovery through the preclinical phase into a manufacturing phase, and making a clinical batch of an HIV vaccine that we can evaluate in Africa. No network or entity has really ever done that. We are the first group of people that will be able to – from the cradle to the grave – go through a process of putting a vaccine into a human being.
What are your primary goals for the BRILLIANT Consortium in the next few years?
At the end of five years, I want to put an African-discovered immunogen into an African-made vaccine platform and deliver the first end-to-end HIV vaccine construct into a human. In the beginning, we will be working with a lot of other people who have been working on African immunogens, but they have been made in other parts of the world and they have been manufactured in other continents because we don’t have the capability. At the end of five years, I would like an ecosystem of HIV vaccine discovery that empowers us from the beginning to the end to make these HIV vaccines and evaluate them in human beings on the African continent.
What are some of the biggest challenges you anticipate in achieving these goals?
There are many challenges, and our biggest challenge at the moment is the lack of mRNA vaccine manufacturing not only on our continent, but at a global level. HIV vaccine research is impeded by the inability at a global level of clinical manufacturing organisations to make clinical-grade vaccines. Therefore, we have to get into queues that can take years to develop at great cost. Our biggest barrier to evaluating HIV vaccines in Africa is just the lack of ability to manufacture, to have mRNA vaccine technology available to us.
The second other biggest factor is just generally the lack of manufacturing capability on our African continent to respond to our needs. We have to work together with global contract manufacturing organisations as well as trying to develop capacity at a local level to do this tech transfer that we would like to do so that if we should be successful, we can go to scale on making vaccines in our continent. For me, the biggest roadblock is the lack of manufacturing capability in Africa.
Another big roadblock is our laboratory infrastructure. There are really great basic scientists on this continent, but they are few and far between for a whole continent. We might have some expertise in South Africa, some expertise in East Africa and expertise in West Africa, but it’s not at the scale that we see in the United States of America. We have to build that laboratory infrastructure, the ability to do pre-clinical work in a rapid fashion, and the ability to move products in a way that the Global North can do.
We are starting at the beginning of the race, but we are determined. For the sake of being trite, there is an African proverb that says, “If you want to go fast, go alone. If you want to go far, go together,” and that is the ethos of the BRILLIANT Consortium. We’ve got community partners, basic scientists, clinical scientists, who are all working together to move this programme forward. And each group are integral because we can’t succeed if there is no community engagement, we can’t succeed if the basic scientists aren’t talking to the clinical scientists and we can’t succeed if we don’t have good clinical data management systems. There is a whole structure in which science happens and without systems to support the rigour of our science, we can’t show that our work was of value. Every part of this puzzle is important to advance the programme forward.
How can the data collected through the BRILLIANT Consortium’s clinical trials contribute to these advancements?
Clinical data is integral for vaccine iteration. Clinical data management is important because, first of all, we want to know that our vaccines are safe. Having a good clinical data management system allows us to capture side-effects, adverse events and general safety of people that are enrolling in our studies, and to put it together so that we can evaluate in a real-time fashion.
The second part of your clinical data management is to evaluate whether your vaccine is immunogenic. When you do your clinical trial, you have to integrate both your clinical data with your immunogenicity data to show how well your immune responses have been evoked by your vaccine. It’s also important because when you do clinical trials, you see that people may respond to the vaccine differently. It gives us an opportunity to look at the people that responded well and the people that responded poorly and try understand who are these people that respond poorly and who are the people that respond well, and try and design our vaccines to focus on that. That’s why it’s important.
The third reason why it’s important is that we have to be able to compare our vaccine against new vaccines that we will be making. Eventually we are going to have to choose a winner. The only way that we can choose a winner is if the way we design our clinical trials, the way we evaluate the safety and immunogenicity, is all the same so that when we look at our trials head-on-head we can say this is a front runner based on the rigour of the clinical data we’ve collected and the laboratory outputs that we’ve got. Data management is integral to doing this.
Good data management is important because regulators – the people that approve our trials – have to be reassured that the data that we are giving to the regulators, to the ethics committees, are robust and reproducible and provide the reassurance that the clinical trials are being run in a way that makes sure that there’s good quality checks, quality assurance and that there’s supervision of safety in a clinical trial.
What role can BioInformatiCo’s data management services play in ensuring the success of these trials?
BioInformatiCo is a very important arm of this whole endeavour. Generally, clinical data management systems have been developed in the Global North and they have been incredibly expensive. We have been unable to afford high quality data management. Developing local data management systems empowers clinical researchers on the African continent to own, control and evaluate their own data. Investing in local African-based companies allows us to develop affordable interventions not only for HIV vaccine clinical trials, but for all clinical trials in the future on our continent.
Despite the challenges, what message of hope would you give to people affected by HIV in Africa and around the world?
There is a great message of hope, because not only do we think that one day our HIV vaccines may be able to prevent HIV acquisition, but we do believe that our vaccines may play an important role in functional cure or the control of HIV without antiretrovirals. By investing in an HIV vaccine, it’s not just investing in prevention. It’s investing in therapeutic options that may minimise the drug burden, the pill burden, the side-effects of antiretrovirals. We do believe that an HIV vaccine will play a critical role both in prevention and treatment.
What are your long-term aspirations for the fight against HIV?
I have been working in the field of HIV since 1993. I have been involved in many clinical trials and trying to evaluate HIV vaccine efficacy. Each trial has taught us something about what we need to do better and how we need to make an HIV vaccine. We’ve come a long way in thirty years. We understand the structure of HIV so much better. We understand the immunology of the host immune response to HIV so much better. I do think that we are on the brink of engineering our HIV vaccine response to produce those durable neutralising antibody responses, that has frustrated, evaded and eluded us for all these years.
People talk of the Moonshot, and I feel like we are at this time in HIV vaccine research. The door has been opened and we are beginning to see the light through the door and what we need to do to move forward. The journey will always be long and hard, but there is no harder vaccine to make. We need the best brains in Africa and we need the kind of funding support that will support this goal of making an HIV vaccine.