A Shot at Change: The Making of a Vaccine

Transcript

The story of the Meningitis Vaccine Project begins, in many ways, in the west African country of Burkina Faso and an 18-year-old named Jean-François.

Marc LaForce
He was the apple of everyone's eye...He was a captain of the local soccer team. He was a wonderful student who won the mathematics medal, and he had what seemed to be an impeccable future. Then one evening he, after doing his studies, went to bed and somewhere around 1 or 2 in the morning, woke up with a terrible headache.

That’s Dr. Marc LaForce, who was stationed in Burkina Faso in the 90s, working on large scale immunization projects. At that time, an epidemic of meningitis A, a highly contagious and often deadly bacterial infection, was sweeping through the region.

Jean-François, delirious and running a high fever, is rushed to a doctor by his mother. Tests are done, and the diagnosis is confirmed: it’s meningitis. Even if he survives, young, healthy patients like Jean-François can walk away from the disease with lifelong side effects.

Dr. Suresh Jadhav
He didn't die, but he lost his hearing.

This is Dr. Suresh Jadhav, executive director of the Serum Institute of India.

Dr. Suresh Jadhav
And four or five years later while playing with his siblings and friends, the ball went on the road and there was a car which was coming from behind who was honking but this boy could not hear it and met with an accident and lost his life.

It’s a tragic, senseless loss. Years later, when Dr. LaForce visits the Serum Institute in India to try and recruit them to a project to develop a vaccine for meningitis A, he tells the story of Jean-François to Dr. Jadhav.

Dr. Suresh Jadhav
He said, "This is something which has moved me." And that story also moved me.

The meningitis outbreak of the late 90s affects something in the range of 250,000 people in sub-Saharan Africa. But developing a vaccine is something that is frankly, not profitable enough for the pharmaceutical industry to bother with.

And that’s where the Meningitis Vaccine Project comes in. Over a period of 10 years, 32 different organizations from around the world, and in particular the global South, work together to develop a new, effective and affordable vaccine for the disease. It’s a group of disparate teams on a global scale, all racing towards a goal that could save thousands, if not millions, of lives. By framing their team as a unified ecosystem of partnerships, instead of individual units coming together, and by making this a truly African-based project, they hope to make stories like that of Jean-François something of the past.

I’m Gabriela Cowperthwaite and this is Teamistry — an original podcast from Atlassian. This show is all about the chemistry of teams – proving that when teams work together, and teams of teams work together, they can achieve more than they ever thought possible.

Meningitis epidemics come in waves. And in the mid-‘90s, in sub-Saharan Africa, there was a big one. It was a particularly brutal period for the 26 countries that make up what is known in medicine as the “meningitis belt.” Here’s Marc LaForce again.

Marc LaForce
Everything pretty much begins in 1996. 1996 was one of the worst meningitis years in Africa. There was probably a quarter of a million cases of group A meningitis that occurred, and it was estimated somewhere in the range of about 25,000 deaths.

The disease moves incredibly fast and is incredibly dangerous.

Ngozi Erondu
In Chad, where I worked, meningitis kills thousands of people every year, and it's a very horrible way to die.

This is Ngozi Erondu. She’s an infectious disease epidemiologist and the CEO of Project Zambezi, a distribution company that gets essential medicines to rural places across the African continent.

Ngozi Erondu
You have a very high fever, a stiff neck and like many diseases, young people but also children as well are affected. So it's quite dramatic and impactful to many people's lives.

There were vaccines available, but they were expensive and not very effective. Typically, they would be deployed as part of a strategy called “reactive vaccination.” An outbreak would occur, and the country’s government would reach out to the World Health Organization, who would then have to source and ship a vaccine. The process was time-consuming and inefficient. Here’s Dr. LaForce again:

Marc LaForce
What was done before that was a strategy that frankly didn't work. More often than not, the vaccine was given long after epidemics occurred, because for the most part, meningitis epidemics within a particular area are over in about six weeks. And it just was logistically impossible to accomplish all of those particular steps within the six weeks. And so the strategies that had been used as these reactive strategies were complex, they were time consuming, they were expensive, and had little to no public health benefit.

Finally, governmental health ministers from around the meningitis belt get together and present their case to the World Health Organization, asking for help developing a solution to this pressing and deadly problem. The idea is to put aside the reactive strategies of the past and develop a vaccine plan that is, instead, preventive—one that stops epidemics before they start.

To do that, they’ll need to immunize millions of people. That means they can’t use the existing meningitis vaccine, which is called a polysaccharide vaccine, as it can’t be used in children under two. It also has a limited life-span of only a couple of years after it’s taken. What’s needed is what’s called a conjugate vaccine. It trains your immune system to recognize and target the bacteria that cause meningitis, stopping the disease before it takes hold.

This conjugate vaccine could be used on children and infants, and it would have long-term protective capabilities. The only problem is that at the time, it doesn’t exist. And that means lives continue to be destroyed and cut short. So in 2001, the Meningitis Vaccine Project is born, led by Dr. LaForce.

Vaccines can save lives by the millions. But developing, testing and manufacturing a vaccine is one of the most complicated and time-consuming processes in medicine. From the very beginning, the team behind the Meningitis Vaccine Project realizes they can’t do it alone. This would have to be a group effort on a massive scale.

Dr. Mark Alderson
It's a very, very complex process developing a vaccine.

That’s Dr. Mark Alderson. He’s a project leader at PATH, a global health organization that was one of the Meningitis Vaccine Project’s major partners.

Dr. Mark Alderson
From research, so identifying the technology to scaling up the manufacturing, to running the clinical trials, to getting the vaccine licensed and then deploying it and making sure that the people that need the vaccine actually have access to it. And that it's made affordably and in appropriate volume. So that's the challenge is bringing together. So no one individual organization typically has all that expertise in house. So the main challenge there is that coordination, identifying the right partners, bringing everybody together and then making sure there's clear understanding of the roles and responsibilities to get the job done.

So, one of the biggest decisions the team makes in the very beginning is to work with their partners, whoever those teams may be, as one unified ecosystem. And that means they need to situate their efforts in the needs of the same people who would be their biggest stakeholders: the people who the vaccine would be developed for. The project begins with an intensive research phase based in the countries of the meningitis belt. Understanding how the disease spreads and the impact it has on society is a crucial piece of the puzzle to immunizing the entire region.

But it’s also important to understand the infrastructure on the ground for actually rolling out the vaccine. Can syringes be procured and distributed? Can the vaccine stay refrigerated and stable on its journey to even the most remote rural area? Here’s Meningitis Vaccine Project leader Marc LaForce again.

Marc LaForce
One of the things that we insisted on from the beginning was that the plans had to be what I call Africa-specific. So during much of the first year of the project, we spent a great deal of time in Africa, understanding the problem, understanding the rigors of vaccine use in Africa, some of the constraints with purchasing problems for products. But we, frankly, became educated, as far as the problem was concerned.

Understanding the needs of the local teams on the ground is crucial to making the project work. Because even though there are multiple groups working on this project, understanding the needs of those who will deliver the vaccine will ultimately help every other team in what they need to do.

One of the biggest challenges to the project in the early days is the question of cost. There are a handful of major vaccine manufacturers in the world. But to make a vaccine financially sustainable from their point of view, a dose needs to cost about $3.50 in US dollars. That’s far too much for the hundreds of millions of doses the Meningitis Vaccine Project needs. There are existing programs in place to get vaccines to countries in need, but not at the scale, speed and low cost required for a project covering 26 different countries.

Epidemiologist Ngozi Erondu.

Ngozi Erondu
So there's quite a few kind of traditional vaccine manufacturers that work closely with WHO, to make sure that certain vaccines are available to Sub-Saharan Africa. There is kind of a process in place for that, but there are still some vaccines that maybe they cost too much to actually develop, or there is not enough profit from the vaccine anyway for the pharmaceutical company of justify why they would bring down the price point and make it affordable and accessible to low and middle income countries that still exist. And so for most of those diseases where that's the issue, either we don't have a vaccine for it, or the vaccine is just literally not available to poor countries.

That’s yet another reason for the project to be Africa-specific. Here’s PATH project leader Mark Alderson:

Dr. Mark Alderson
One of the unique factors about this particular vaccine was it was the first vaccine developed that was specifically targeted to Africa. And so normally vaccines get developed for the developed world, high income countries, and then they slowly make their way down. So there's a lot of history behind them. A lot of acceptance in other countries. Here, this vaccine is targeted to Africa. And therefore, I think we had to make sure that there were not perceptions about the quality of the vaccine. It had to be cheap, but it had to be high quality.

In the winter of 2001, there’s another meningitis outbreak, this time in Benin, Chad and Ethiopia. Thousands are infected and hundreds die.

The vaccine needs to work. It needs to be manufactured at an enormous scale. And it needs to cost less than 50 cents a dose. None of the big pharmaceutical companies want to touch the project because it doesn’t meet their threshold for profit. The vaccine group realizes they’re going to have to take an alternative route. And to do that, they’ll go to India.

In the spring of 2002, the Meningitis Vaccine Project decides that the best way forward is to become a vaccine company themselves—meaning that instead of relying on the established approach of getting a pharmaceutical corporation to develop a vaccine for them, they’ll bring manufacturing into their team.

They soon settle on a prime candidate, the Serum Institute of India. Founded in 1966, the Institute is actually the world’s largest vaccine producer, manufacturing over a billion doses a year. And crucially, as an institution in the developing world, they’re more sensitive to the financial realities of some African nations than other big pharmaceutical corporations. The 50-cent vaccine won’t scare them off.

Marc LaForce gets on a plane to the Institute’s headquarters in the city of Pune and meets with Dr. Suresh Jadhav, the executive director of the Institute. Here’s Dr. Jadhav:

Dr. Suresh Jadhav
And Marc personally believed that if he can sort of get commitment from a developing country manufacturer, and one of the major reasons why developing country manufacturer, was that our idea of making profit is different than the idea of making profits by the big pharma. And because at that time, Serum Institute was one of the few manufacturers who was the first one from the developing world to get the WHO prequalification.

In other words, to support the project’s success, they choose the right partners. A mismatch in priorities or cultures could be disastrous with an effort of this scale. For teams to work together, they need to be aligned on a fundamental level. With Dr. Jadhav as the project’s champion, the Serum Institute agrees to partner with the Vaccine Project.

The biggest jobs are still ahead of them. They’ve got to continue to study the disease on the ground, produce a life-saving vaccine, distribute it and make sure it’s administered properly to hundreds of millions of people. And that involves a lot more partners. Huge entities like the World Health Organization and UNICEF, health ministers from small nations, and public health groups with long histories of treating meningitis: in total, more than 30 groups join the effort.

Working with that many partners is not easy. Mark Laforce realizes that to manage these new relationships requires respect and acknowledgment.

Marc LaForce
And so we just wanted to make sure that everybody understood and was recognized for what they were accomplishing, whether it was UNICEF, WHO, médecins sans frontières, whether it was groups that were actually doing the clinical trials themselves. It didn't make any difference. Everybody was important.

One strategy the project leaders employ is making sure each participating organization is included and knows they are influencing progress. This becomes an incredibly important way of creating buy-in among stakeholders. Everyone wants to feel like they belong and are listened to—lose that and the project could fall apart.

But these check-ins aren’t enough. The vaccine could go off the tracks if the goals and priorities of each team within the project aren’t recognized and supported. For some, like the Serum Institute, it can include financial issues: do they have enough cash flow to keep the lights on? In other situations, academics working on the project might need to publish papers to keep their careers on track.

The Vaccine Project is able to keep this massive endeavour working smoothly by making sure that progress not only furthers development of the vaccine, but also helps individual partners reach their own goals. Over five years they manage the enormous feat of developing the conjugate vaccine technology, maintaining constant on-the-ground surveillance of meningitis activity in West Africa and planning for the vaccine’s eventual rollout.

And although it’s a global effort, it’s based in Africa and India. As such, the project is an example of countries from the global South cooperating to produce a truly successful South-South partnership. Epidemiologist Ngozi Erondu.

Ngozi Erondu
It's just the idea that there's always this kind of reliance on the global South to the global North, and there needs to be stronger partnerships throughout emerging markets actually. The income disparity is much more different in India and in the country like Nigeria than in a country like the United States. And so those companies, those industries, they have to develop different tiers of pricing, and for much of their pricing, it's a much lower tier, it's much more affordable. They have to do different things in order for their population to access their medicines and their vaccines and things like that. And so I think that this really, to me, should really spur more South-South collaboration.

Dr. Samba Sow
So, the South-South has been really really really the best part of this.

This is Dr. Samba Sow. He’s the director general of the centre for vaccine development in Mali, and he’s been involved in the Meningitis Vaccine Project since 2005.

Dr. Samba Sow
We managed to really benefit from Indian researchers, investigators. So, we were trained by them many, many times on how to manage a trial. When talking about data monitoring, when talking about data quality, we're talking about actually data entry and data management, data analysis. So that was really a good benefit South-South. And, they also managed to visit our sites and get exposed to our challenges and also share their local challenges with us. So, it was a great collaboration between us.

In typical North-South healthcare partnerships, the North leads and the South follows. But this South-South collaboration creates a template for a new kind of relationship, where a lead team doesn’t need to be orchestrating everything. Where various partners, who seem less likely to play a leading role, can have a seat at the table. And that the global south is, of course, able to take that leadership role.

It’s 2005, and a vaccine prototype is ready to go to trial. It’s called MenAfriVac—the ”Meningitis Africa Vaccine.” It’s tested successfully on 74 adults in India, and then the following year, trials are rolled out in parts of Africa.

One of the biggest challenges is convincing a skeptical public that the vaccine project has their best interests at heart. The project leadership immediately recognizes that keeping these stakeholders informed and happy is crucial to the team’s success. In Mali, Dr. Samba Sow oversees the trial process. It’s not always easy.

Dr. Samba Sow
When it comes to medicine and modern medicine, in many African settings, even routine activities are always bad rumors and cultural, socio-cultural barriers. So, during these trials we were facing some key issues. One is, that the fact that the targeted population for this trial was age between 2 and 29. So people were thinking that the reason we selected that age range was that we, when we vaccinate you're at 2, so when you reach the age of 29, then you will die. And before you reach that age, you will suffer from HIV. You will lose your hair and all the girl babies will become sterile. So these were the type of rumors that were made up, are coming out of different communities.

The team realizes they need to respond immediately to these rumours. Marc Laforce and Suresh Jadhav come to Mali and meet with the community. Dr. Sow reaches out to the community leaders and sets up a meeting in a local mosque.

Dr. Samba Sow
And right after the prayer they allowed Marc and Dr. Jadhav to be in the mosque and to sit down with us. Then we all went in to sit down with the Imams and the leaders. And then, we started to explain to introduce ourselves. And then to explain the study and then to explain all the procedures. And then to explain, try to troubleshoot the rumors. And then, sit and listen to the questions up until we had reached a point that people were starting to smile and say, “Ah, now I see. Oh, yes. Oh no, this is good.” So, when it comes up to this point, then everyone was happy.

In the past, and still today, communicating public health issues in parts of Africa can be problematic because outsiders might try to foist their point of view on locals. But in the case of MenAfriVac, the group, which does include outsiders, is instead explaining what they are doing in the context of how locals are living their lives. So that the people affected by the crisis also become part of the project ecosystem. By addressing their needs and fears and hopes.

By 2010, after nearly a decade of work, including successful trials on the ground in Mali and other African countries, the project finally has the MenAfriVac vaccine in hand. Not only does it appear to safely protect against the disease, it’s groundbreaking in other ways as well: it can last up to four days without having to be refrigerated, making it much easier to get to far-flung communities.

The next challenge is actually rolling it out and immunizing the population. Medical workers will need to be trained to administer it properly and safely. Fortunately, the Serum Institute has experience with exactly that. Here’s Dr. Suresh Jadhav:

Dr. Suresh Jadhav
When meningitis project was launched they did have to train these people to immunize the adults and immunize. Once you are used to immunize the child, immunizing adult is not difficult, but it is the discipline and the training, getting those people at the immunization center, making them sit properly and follow the discipline that after the immunization, they should sit for another 15, 20 minutes to see that there are no any adverse reactions. So this kind of training takes a lot of time. But Serum had some experience of that. So we did share that experience also with the people at MVP.

With teams on the ground properly trained to administer the vaccine, over 20 million people are immunized in the first four weeks. Gradually, that number expands to over 270 million. And the results are astonishing.

In the regions where the vaccine has been administered as part of the standard public health protocols, Meningitis A has virtually disappeared. Dr. Samba Sow.

Dr. Samba Sow
I can tell you in Mali, since the campaign, there has been zero cases of men A has routinely. And during the campaign in 2009, 2010, all the way down to now, all very countries where campaign happened, among the vaccinated cases, there were zero cases, still zero cases. So, with this vaccine I could say that we managed to eliminate meningitis A as a public health problem in sub-Saharan Africa.

The effort to eradicate disease in sub-Saharan Africa is in many ways, just beginning. There are strains of meningitis that still threaten the population, as well as diverse other diseases. But the teamwork of the Meningitis Vaccine Project has provided a rock-solid foundation for continuing efforts. A second vaccine, aimed at those other strains, is well on its way to being licensed in the next year or so.

As organizations around the world, including the Serum Institute of India, race to find a vaccine for the virus that causes COVID-19, the story of the Meningitis Vaccine Project could be a blueprint for future vaccine development.

Dr. Samba Sow
We should learn from what we did with MVP. We must. I mean it's even not should. We must use our past experience to overcome the actual challenges. COVID-19 will never be able to end by only one country. Even if you are so powerful, you have so much money. This virus doesn't care about how powerful you are. You see all the so-called, so well-developed countries, they are suffering. Millions of cases in those countries. So, if we want to overcome COVID, we must use examples like meningitis vaccine trial that we used to kill this large outbreak in sub-Saharan Africa, the most difficult area.

The Meningitis Vaccine Project was successful because it rewrote the template when it comes to making and distributing a vaccine. Those first few groups on the ground in Mali, Burkina Faso and other African countries realized they couldn’t do it alone. By finding others like the Serum Institute and PATH, groups with shared values, stakeholders became partners, not vendors. This all meant the outcome, MenAfriVac, was everything the core team could have hoped for. And with the very real challenges and dangers that epidemics present to the world today, perhaps this model can inspire others.