Weeks after the global public health community sounded the alarm on the shortage of cholera vaccine, the World Health Organization moved to prequalify a new cholera vaccine last month. The vaccine is a simplified version of the two existing oral vaccines, both produced by Korean vaccine manufacturer EuBiologics Co.
The company will begin making the new vaccine, called Euvichol-S, this year. “We simplified the formulation, which reduces the complexity, the cost, and the time for producing the vaccine,” said Julia Lynch, the director of the cholera program at the International Vaccine Institute, a nonprofit that codeveloped the cholera vaccines with EuBiologics Co. “With this simplified formulation, it’s expected that we’ll increase the production capacity by about 40% — using the same personnel, the same facilities.”
Along with a new manufacturing plant that will be at full capacity next year, EuBiologics will be able to produce 50 million cholera vaccine doses in 2024, and 80 million in 2025, said Lynch — most of which will be Euvichol-S. But even this increase in production may not be sufficient to address the surging global demand.
A combination of natural disasters, conflict, and climate change have driven cholera cases up in recent years, with preliminary data reporting nearly 700,000 cases in 2023, more than triple the number in 2021. Reported cases are just an indicator: Estimates of actual infections range from 1 million to 4 million a year.
Daniela Garone, international medical coordinator at Médecins Sans Frontières and a member of the International Coordinating Group on Vaccine Provision, told STAT that the increased supply for 2024 was already part of the ICG’s forecast, and won’t be sufficient to fill the supply gap this year. Though the burden of cholera seems to be easing slightly in 2024, countries have already requested nearly 80 million doses of vaccine this year — and that’s after adopting a one-dose protocol to stretch supply.
The projected production capacity may be sufficient for a single-dose regimen next year, Garone said, but there are too many variables in play to know for sure, including whether plants meet their projections.
“What we don’t know is this large surge in outbreaks, which began maybe in late 2021, 2022 — whether this is a new normal and this incredible demand right now will be sustained, or whether this is a phenomenon that will reset over the in the next few years,” said Lynch. “That, of course, makes manufacturers anxious.”
A resilient supply of any vaccine typically requires at least three separate manufacturers, according to international vaccine alliance Gavi. The cholera vaccine used to have two. But in 2022, Sanofi stopped producing its cholera vaccine, which contributed 15% of the global stockpile, leaving EuBiologics on its own.
This is expected to change in 2026 or 2027, said Lynch, as the International Vaccine Institute transfers manufacturing of the new, simplified vaccine to two companies in South Africa and India.
Biovac, in South Africa, has already completed the technology transfer process, as IVI shares the vaccine composition and the know-how to produce it, and is working on developing manufacturing capacity. “It takes quite a bit of time to develop the manufacturing capacity and what we call ‘scale up’ to a commercial size. And then, of course, they have to do a clinical trial,” said Lynch: Though the new manufacturers are replicating an existing vaccine, their product is still subject to quality and efficacy testing.
Once all that is done, Biovac is expected to produce about 10 million doses a year. “It would be the first end-to-end vaccine production on the continent, which is very exciting,” said Lynch. The second transfer is still in progress to Biological E, an established Indian manufacturer that is also expected to produce 10 million to 15 million doses on a similar timeline.
Sharing technology with low- and middle-income countries remains a point of contention for the pandemic accord discussed this week by country health delegations at the WHO. Big drug manufacturers have long argued that sharing know-how with manufacturers in low- and middle-income countries can put the quality of vaccines at risk.
The cholera vaccine transfer challenges that notion, said Ellen ‘t Hoen, the director of Medicines Law and Policy, a research organization focused on access to medicines. “It is well known that many of those middle-income countries have very sophisticated vaccine production capacity, and some even vaccine development,” she said. Having a cholera vaccine entirely made in the African continent, she said, is not only evidence that there can be quality assurance outside rich nations, but an encouraging proof of concept for the role of low- and middle-income countries in increasing the global vaccine production capacity.
That’s exactly what IVI was built to do, Lynch emphasized. In 1996 a U.N. charter established the institute for the very purpose of developing vaccine technologies for diseases of global public health importance. “Our role is to license them, but it’s a very low-cost license, and then we help the companies establish the production,” she said. “This is what we do. It’s not a sideline, it’s what we do.”