Editor's note: this article provides a historical overview of PATH's groundbreaking, multi-year project to produce and deliver the MenAfriVac® vaccine.
A groundbreaking partnership
In 1996 and 1997, the largest meningitis epidemic in African history swept across sub-Saharan Africa and 25,000 people died. It was the final straw.
After a century of living through recurrent meningitis outbreaks (plus 30 years of experience with a logistically difficult polysaccharide vaccine), the epidemics were still growing more deadly by the year. African ministers of health knew that something needed to be done so they turned to the World Health Organization (WHO) for a solution.
WHO responded to the African ministers by bringing together global health leaders to discuss developing a new, more potent vaccine—one that could provide long-lasting protection against meningitis in Africa and could be used preventively. In 2000, delegates from African and Eastern Mediterranean countries, multilateral organizations, vaccine manufacturers, and the scientific community determined that developing a low-cost conjugate vaccine to fight group A Neisseria meningitidis, the leading cause of the epidemics in the meningitis belt, was indeed possible—and that it was a priority.
A year later, the Bill & Melinda Gates Foundation provided a ten-year grant to establish the Meningitis Vaccine Project (MVP), an award-winnning partnership between PATH and WHO that would lead the development, testing, licensure, and widespread introduction of a conjugate vaccine with the promise of protecting millions of lives from group A meningococcal meningitis.
Although the scientific experts convened by WHO believed a conjugate meningitis vaccine could become a reality, the challenge for MVP was daunting. How would this partnership between two public health organizations gain access to and license a conjugate vaccine technology? And moreover, how would the partnership be able to develop a vaccine that the countries of the meningitis belt could afford?
In 2001, newly appointed MVP director Dr. Marc LaForce met with African public health officials to talk about the vaccine, and the question of cost came clearly to the forefront. “Please don’t give us a vaccine that we can’t afford,” an official from Niger told LaForce. “That’s worse than no vaccine.”
“ Please don’t give us a vaccine that we can’t afford. ”
Local officials made it clear that the vaccine needed to cost less than US $0.50 per dose to be sustainable in the countries where it would be used. But as the MVP team began meeting with pharmaceutical companies to discuss developing an affordable conjugate meningitis vaccine, LaForce and others soon realized that no one in the developed world could produce it at the desired cost. They began exploring alternatives.
Dr. S.V. Kapre, executive director of the Serum Institute, said MVP leaders were struck by the goal of creating a vaccine that would address a huge need in the developing world. “Making a vaccine is a technical issue, but making the vaccine available at an affordable price is a real challenge,” Kapre said. Unless that challenge is met, the problem of meningitis won’t be solved because the people who need the vaccine won’t be able to afford it. So Serum made a conscious decision to be as frugal as possible to meet the vaccine price requirements, he said.
The product development plan
In 2002, the Meningitis Vaccine Project (MVP) found a way to produce a conjugate vaccine at less than the price point African countries had identified as affordable: By partnering with the Serum Institute of India Private Ltd., a developing-country vaccine manufacturer.
With the Serum Institute on board, the MVP team put together an innovative product development plan where the raw materials came from one source, the technology from another, and the manufacturing capability from a third. With this plan, they could produce a meningococcal A conjugate vaccine MenAfriVac® at less than US $0.50 per dose.
PATH team members turned to the Serum Institute and Synco BioPartners in Amsterdam, the Netherlands, to supply the raw materials (the protein tetanus toxoid and the group A polysaccharide antigen). With the raw materials suppliers in place, the team next needed access to the conjugation technology—intellectual property that is valuable and highly protected. “This was not easy to resolve early on,” MVP director Dr. Marc LaForce said.
“ Everyone believed in the mission. ”— Marc LaForce
Up next was a partnership with the Center for Biologics Evaluation and Research at the US Food and Drug Administration. Dr. Robert Lee and Dr. Carl Frasch, two scientists at the center, had developed a new conjugation method that could be used to produce the vaccine. MVP acquired the technology and, with help from the National Institutes of Health, transferred the technology within months to the Serum Institute at almost no cost.
“Everyone believed in the mission,” LaForce noted, crediting this collective passion for the relatively quick timeline of the project.
Beyond vaccine development
To successfully introduce a new vaccine to sub-Saharan Africa, the Meningitis Vaccine Project (MVP) had to work two sides of an intricate equation: Considering the vaccine’s scientific merits, as well as how it would be introduced into Africa once it was approved. The work involved simultaneously developing the conjugate vaccine, meeting the rigorous regulatory and technical rules that govern the production and testing of new vaccines, setting up clinical trials to test the safety and efficacy of the vaccine, and strengthening countries’ ability to host clinical trials and to administer the vaccine, once available.
To meet these challenges, the MVP team formed three partnerships very early in the project:
- A panel composed of pharmaceutical and clinical trial experts that oversaw the development of the vaccine and provided guidance on choosing a manufacturing partner.
- A group of consultants with expertise in carbohydrate chemistry, vaccine regulatory issues, and pharmaceutical development that helped to address specific questions or problems that arose as the vaccine was developed.
- A WHO project advisory group, made up of senior African public health officials, that advised MVP on the choice of African clinical trial sites and the design of the clinical trials.
Besides providing key technical know-how and guidance, this strong network of support also helped MVP overcome initial skepticism from others in the scientific world that a meningococcal A conjugate vaccine could indeed be produced at a cost African countries could afford.
In 2005, after two years of careful, detailed work to perfect the conjugate vaccine, the MVP team launched the first clinical trial to evaluate the vaccine in humans. Seventy-four healthy adults in India took part in the phase 1 trial, which showed the vaccine’s safety and immunogenicity.
In 2006, as a new epidemic wave swept over the meningitis belt, the MVP team launched a more intensive phase 2 trial in Africa to evaluate the vaccine among a younger age group. A year later, more good news: The pivotal study confirmed that the conjugate vaccine was safe and demonstrated that it produced antibody levels almost 20 times higher than those obtained with the marketed polysaccharide vaccine used in reactive immunization campaigns. These encouraging results cleared the way for more studies among age groups and populations that would eventually be targeted by the mass campaigns.
By 2009, the MVP team had enough clinical data to submit the vaccine dossier to the Drugs Controller General of India for Indian licensure and to WHO for pre-qualification for use in Africa. The vaccine was nearly ready for introduction.
To prepare for introduction once the vaccine became available, the MVP team began to build countries’ capacities to integrate the vaccine into their health programs. In the countries hardest hit by meningitis, WHO led the strengthening of disease surveillance and enhancing of laboratory capacity to provide up-to-date information about meningitis outbreaks and improve the data base necessary for vaccine introduction.
In addition, the MVP team collaborated with in-country partners to train staff and develop know-how for conducting clinical trials, ensuring they would have the skills and capacity for managing not only studies of the conjugate vaccine but future studies of other new vaccines or drugs in development.
To build understanding of the vaccine among the populations of the meningitis belt countries, the MVP team reached out to journalists, national officials, health workers, and communities with information and training about the disease and the vaccine. The team also developed an online e-learning tool specifically for immunization managers in developing countries to receive comprehensive, interactive information on meningococcal meningitis and the new conjugate vaccine.
Bolstering all these efforts was the historic Yaounde Declaration, issued by the ministers of health of meningitis belt countries on September 4, 2008, during a meeting in Cameroon. The declaration pledged the ministers’ commitment to fast-track introduction of the new vaccine once it was approved for widespread use and to strengthen disease surveillance, control plans, and information-sharing across borders to collectively enhance the region’s response to meningitis.
Ready for launch
In 2010, the MenAfriVac® vaccine cleared its final regulatory hurdles. First, the Maharashtra State Food and Drug Administration in India granted Serum Institute marketing authorization to export and use the vaccine in Africa. Then, after a detailed evaluation, WHO announced prequalification of the vaccine, certifying that it met international standards of quality, safety, and efficacy.
On December 6, 2010, countrywide vaccination campaigns with MenAfriVac began. By the end of the year, the campaigns had reached 20 million people in Burkina Faso, Mali, and Niger, three of the most affected countries of the meningitis belt. The next year, the vaccine was launched in three more countries. By the end of 2016, it had reached 19 countries in the meningitis belt. The campaigns were a stunning display of mass mobilization and the region’s commitment to eliminating the disease. Less than 15 years after the creation of MVP, a vaccine is on the cusp of fulfilling a promise: To end deadly and debilitating meningitis A epidemics.
A hopeful future
The MenAfriVac® vaccine was developed in record time and launched in communities across Africa’s meningitis belt just as quickly. In six years, more than 270 million children and adults, ages 1 through 29, have been vaccinated across 19 countries of sub-Saharan Africa.
The vaccine quickly reduced the transmission of meningococcal bacteria and created a drastic drop in illness and death rates from meningitis A. Widespread coverage of the vaccine created “herd immunity” that protects even those who have not been vaccinated against the disease. Immunity with just one dose of the vaccine can last as long as ten years.
PATH and WHO also built evidence for MenAfriVac’s safe use among infants. The vaccine received WHO prequalification—which brings international regulatory approval—of the meningitis A conjugate vaccine for infants in 2015, clearing the way for its use among the youngest people susceptible to the disease.
The vaccine broke another important barrier. Tailor-made to withstand hot climates, it was the first vaccine in Africa allowed to be transported and stored for as long as four days without refrigeration or an icepack, easing delivery and making it possible to reach even the remotest of communities.
MenAfriVac was developed at a major cost savings—less than one-tenth the cost of the US$500 million typically needed to bring a new vaccine to market. In addition, the reduction in meningitis cases is expected to free up significant funds that countries can use to address other public health problems.
Generous funding allowed the vaccine to be introduced in mass immunization campaigns across the meningitis belt. However, funding is still needed to ensure that the vaccine is included in countries’ routine immunization programs so that infants are protected and there is no resurgence.
The Meningitis Vaccine Project has concluded, but PATH’s work goes on. We are collaborating with in-country and global partners to ensure the sustainable use of MenAfriVac and the long-term control of meningitis A epidemics. We are also partnering with Serum Institute of India Private Ltd. on a new vaccine—one that would protect against all forms of meningitis that cause illness and death in the meningitis belt.
With MenAfriVac, we proved that it is possible to put meningitis A on the run. Now we are working to ensure that all communities in the region receive a historic, lifesaving dose—and applying the lessons learned to create the next generation of vaccines.
MenAfriVac is a registered trademark of Serum Institute of India Private Ltd.