Cholera vaccine doses are being given to patients as fast as they can be produced and the global stockpile has completely dried up, while the deadly disease outbreak continues to spread.
This comes as no surprise to anyone in the field of emergency response to the epidemic because the vaccine stockpile has been very low for years.
The surprise — the good news, which is surprising because ‘cholera’ and ‘good news’ are rarely used together — is that three new vaccine makers are setting up production lines and joining forces to replenish the stockpile.
And a fourth company, the only current maker of the vaccine, which is given orally, is working at a pace experts describe as “heroic” to expand its production.
But despite all this, the total global vaccine supply that will be available this year is, at best, a quarter of what is needed.
By the end of February, countries had reported 79,300 cases and 1,100 deaths from cholera this year. Since there is no consistent system for counting cases, this is likely a gross underestimate.
In October 2022, the organization that manages the global emergency cholera vaccine stockpile made an unprecedented recommendation that people receive only one dose of the vaccine instead of two in an effort to expand the supply. A single dose of cholera vaccine provides between six months and two years of immunity, while the full regimen of two doses delivered one month apart gives adults about four years of protection.
Last year, countries sent requests for 76 million doses of the vaccine for single-dose “reactive campaigns” — efforts to vaccinate people in areas with active outbreaks.
There are only 38 million doses in the stockpile, so only half of the requests are filled, and those are only for a single dose. There are no vaccines left for preventive campaigns that would ideally be carried out in places like Gaza, where all the conditions for large outbreaks exist, or in places where cholera is endemic.
The race to produce more cholera vaccine illustrates all the reasons why it is so difficult to respond to epidemics even with the participation of dedicated drug makers who are not afraid of the small profit in a vaccination that is mostly for to the poor.
Cholera can cause death by dehydration in as little as a day as the body tries to expel the toxic bacteria in streams of vomit and watery diarrhea. The disease is spread through contaminated drinking water. Current outbreaks are driven by the spread of conflict and climate disasters that force people into cramped living situations without adequate sanitation systems. In recent months, there have been outbreaks in 17 countries, including Afghanistan, Zambia and Syria.
But demand has only grown since then.
The South Korean company EuBiologics is currently the only company in the world that produces a cholera vaccine. The company has known for some time that there would be pressure on the supply of the vaccine because the only company that made it, an Indian subsidiary of the drug company Sanofi, announced in 2018 that it would end production of the vaccine, which was its in 2023.
To cover the gap in vaccine production, Rachel Park, the director of international business at EuBiologics, said the company decided to try to simplify its vaccine formula, streamlining steps and ingredients to make it more multiple doses faster.
The company was then making more bulk drug products than it could quickly put in the tubes, so it contracted with a second Korean firm to help.
EuBiologics has also invested in building a second manufacturing site that will double the amount of vaccine the company can produce. The company took the long and expensive step of having both the simplified vaccine and its new facility approved by the World Health Organization in a process called prequalification, which means countries no longer have to administer their own tests. in regulation. When the new plant begins production, the company will be able to produce up to 46 million doses a year.
“EuBiologics is really the unsung hero of the story,” said Dr. Julia Lynch, the director of the cholera vaccine program for the International Vaccine Institute, a United Nations-supported organization based in Seoul. “They are doing everything they can to get volumes as fast as possible.”
Together, these measures should increase production to a total of about 46 million doses this year, and to about 90 million doses in 2025 and beyond, Ms. Park. But that’s probably still less than the world needs.
“Doses are allocated before they are even made,” said Dr. Daniela Garone, the international medical coordinator for Doctors Without Borders sits on the committee that decides which countries will receive the doses, and how many. “We didn’t expect it to be any better this year, but we didn’t expect it to be any worse.”
There’s more hope on the far horizon: Three more drug companies have cholera vaccines in their pipeline. The International Vaccine Institute has licensed its vaccine to Biological E, an Indian firm, and shares the formula and equipment for its manufacture. The WHO
In South Africa, a company called Biovac is about to begin clinical trials on what could be the first vaccine made from start to finish in sub-Saharan Africa. Biovac hopes to complete the trials by 2027. After that, it will likely take at least a year for the vaccine to receive WHO prequalification, Dr. Morena Makhoana, the chief executive of Biovac.
Bharat Biotech, another large Indian company with large production capacity, produces its own oral cholera vaccine. It could bring its vaccine to market by the end of 2025.
To encourage companies to invest in the production of cholera vaccines, Gavi, the international organization that supplies vaccinations to low- and middle-income countries, has indicated the possibility of initial market commitments – the commitment of future orders that would encourage drug makers to invest in cholera vaccine production. Gavi pays EuBiologics $1.53 per dose for the vaccine.
Bharat and Biological E both plan to produce about 15 million doses per year initially, Dr. Lynch – “moderate volume” by the standards of these large Indian companies that could do more if the market continues to grow.
Potential demand is difficult to predict, he said. “That’s really the question: Is what the world is going through right now some kind of phenomena of a few years that was triggered by something?” said Dr. Lynch. “Or is this the new normal? Is this a new kind of set point?”
