There are no vaccines for mpox available in Congo, the epicenter of a global health emergency declared last week, even though the country first asked for the shots two years ago and the manufacturers say they have supplies.

“The most important thing we need right now are the vaccines,” said Dr. Samuel-Roger Kamba, health minister of Congo.

So where are the shots? They are trapped in a byzantine drug regulatory process at the World Health Organization.

Three years after the last worldwide mpox outbreak, the WHO still has neither officially approved the vaccines — although the United States and Europe have — nor has it issued an emergency use license that would speed access.

One of these two approvals is necessary for UNICEF and Gavi, the organization that helps facilitate immunizations in developing nations, to buy and distribute mpox vaccines in low-income countries such as Congo.

While high-income nations rely on their own drug regulators, such as the Food and Drug Administration in the United States, many low- and middle-income countries depend on the WHO to judge what vaccines and treatments are safe and effective, a process called prequalification.

But the organization is painfully risk-averse, concerned with a need to protect its trustworthiness and ill-prepared to act swiftly in emergencies, said Blair Hanewall, a global health consultant who managed the WHO approvals portfolio as a deputy director of the Bill & Melinda Gates Foundation, a key funder, for more than a decade.

“They don’t have flexibility to use alternative approaches,” she said.

There have been more than 15,000 cases of mpox in Congo this year, and at least 550 deaths, although many cases are not diagnosed or treated. Most of those deaths have occurred among children, some of whom starve because agonizing lesions in their mouths and throats have prevented them from eating.

A new variant of the virus, spread by close intimate contact, has now crossed Congo’s eastern border into 13 countries, prompting the WHO to declare a global health emergency on Aug. 14.

Paul Chaplin, CEO of Bavarian Nordic, which makes the Jynneos vaccine that was widely used in North America and Europe during the mpox outbreak in 2022, said the company has 350,000 shots it could sell immediately.

The company can produce 10 million more doses by the end of 2025, he said — but there are no orders. This week, under pressure from member states, the WHO signaled to Gavi to start a purchase negotiation with Bavarian Nordic even though vaccine approval is still pending.

The WHO says that, until this extraordinary measure, it had been bound by the rules: It has not had the data it requires to do a full review for approval of Jynneos, and the emergency license process can be carried out only after a public health emergency of international concern (known as a PHEIC) has been declared, which just occurred.

But Bavarian Nordic first met with the WHO in August 2022 to discuss Jynneos, and submitted a dossier of information on the vaccine in May 2023, according to Chaplin.

That dossier contained the research that led to approval years ago from the European Medicines Agency, as well as data from studies carried out once the vaccine was deployed during the 2022 mpox outbreak.

More than 1.2 million people in the United States received at least one dose of the vaccine at that time, and studies showed it provided a high level of protection against mpox. Yet the WHO did not open formal consideration of that research until last week.

Deusdedit Mubangizi, the WHO’s director of health product policy and standards, said that the organization’s group of experts would meet the week of Sept. 16 to consider the submitted data, and could issue a license as early as that week if they were satisfied.

In recent weeks, key players in the epidemic response have grown increasingly critical of the WHO for unnecessarily slowing the effort to get vaccines to Africa. It’s a “broken system” that “is not built for emergencies,” said one U.S. scientist who sits on WHO advisory panels but was not authorized to speak publicly.

Critics question why the WHO did not act sooner to approve an mpox vaccine, since the virus has never stopped circulating in Congo. And they ask why it has not been possible to give the shots an emergency license based on the U.S. and European authorizations of the Jynneos vaccine.

The vaccine was originally created to prevent smallpox and had been kept in biosecurity stockpiles after the eradication of the disease. Because mpox, like smallpox, is part of the orthopoxvirus family, researchers thought smallpox vaccines might work to block mpox. There were small studies in animals that showed it was effective.

Although there were no human trials, drug regulators in high-income countries moved quickly to allow emergency use as mpox began to spread in Europe, North America and South America in 2022.

But Mubangizi said it was not possible for the WHO to approve the vaccines at that time. “We could not prequalify them, because there was no data to support” their effectiveness against mpox, he said.

And the WHO decided not to issue an emergency license back then because it wanted to ensure that research data was generated, he said. Authorizing widespread use would have cost researchers that essential opportunity.

Then, spread of the virus slowed or ended everywhere outside Congo, and attention to the vaccine dissipated.

This year, as case numbers grew in Congo, the WHO decided to trigger the emergency license process even as it declared a global emergency. “We immediately got in touch with manufacturers and told them to submit a formal application,” Mubangizi said.

KM Biologics, a Japanese pharmaceutical company that makes an mpox vaccine called LC16, submitted its dossier Friday. Bavarian Nordic offered additional information regarding what the WHO calls “programmatic suitability for use,” he said.

This refers to aspects of the vaccine that may influence how it can be used in different settings. The Jynneos vaccine, for example, needs to be stored at minus 20 degrees Celsius, but not all health centers in a country such as Congo will be able to keep vials of it that cold. Regulators in high-income countries do not typically evaluate a vaccine with these kinds of considerations.

Most of the data collected on the Jynneos vaccine evaluated it for use on the Clade 2 mpox virus, a less lethal version that caused the 2022 global outbreak. But the Clade 1 virus is circulating in Congo and across East Africa, and the vaccine has not been tested against it.

“We are not sure the efficacy on Clade 2 is transferable to Clade 1 — nobody has that information,” Mubangizi said.

Congo’s own drug regulator approved Jynneos and the LC16 vaccine on June 27 — long after Nigeria, which had many mpox cases in the 2022 outbreak, did an approval of its own.

The lengthy delay raised eyebrows in health agencies supporting Congo, but Kamba, the health minister, said the country has limited resources and a host of crises.

“We have a lot of emergencies on our hands,” Kamba said.

Congo currently has outbreaks of measles and cholera, as well as a severe malaria problem that threatens small children. Hundreds of thousands of people live in camps because they have been displaced by ongoing armed conflicts.

Because Congo has approved the vaccines, the country can receive donations — 215,000 Jynneos doses are set to be shipped to Congo in the coming weeks, Kamba said.

There are 175,000 doses donated by the European Union, and 40,000 more by Bavarian Nordic. The U.S. government has pledged to donate 50,000 Jynneos doses from its national stockpile.

Congo could simply buy mpox vaccines. But the Japanese vaccine is complicated to administer — requiring a rare specialized needle — and the Danish vaccine is expensive. In 2022, Bavarian Nordic was selling it for about $110 a dose. Full vaccination requires two doses.

As a low-income nation, Congo qualifies for support from Gavi, which has a $500 million pandemic emergency response fund earmarked for situations such as this.

Chaplin would not say what price Bavarian Nordic planned to offer Gavi. “There is room to maneuver, but it’s based on volume and commitment,” he said.

“If the international community were to say, ‘OK, we’re going to buy X doses a year because we want to start vaccinating children in Africa’ — that changes everything,” he added.

With that sort of commitment it would be worthwhile for the company to work with a contract manufacturer based in Africa, Chaplin said. That firm would produce the vaccine at a much lower price while paying a royalty to Bavarian Nordic.

But Gavi has been waiting for the WHO’s emergency authorization to begin the process.

“The first priority needs to be getting donated vaccines that we know are available into countries,” said Dr. Derrick Sim, Gavi’s managing director for vaccine markets and health security.

“When it comes to procuring vaccines directly, since a PHEIC was announced last week, we have intensified our efforts, with near-daily contact with manufacturers,” he said, referring to the global health emergency. “We are ready to go as soon as we get a clear picture on demand.”

Some experts now wonder why Gavi should wait for WHO approval of vaccines at all.

“That would not be a complicated thing for the Gavi board to change, if they wanted to move faster in an emergency,” said a U.S. global health official who was not authorized to speak publicly about the matter.

A process for the WHO to prequalify drugs without a full review of the research already exists. The organization has approved more than 100 medications, mostly antivirals to treat HIV, based on FDA review, for their use in Pepfar, the U.S. government’s program to treat that virus in African countries.

There is reason for caution. Dr. Placide Mbala, director of the clinical research center at the National Institute of Biomedical Research in Kinshasa, said he had hopes for the vaccines, but it was an open question how well they will work with the variant of the virus now circulating in Congo.

Mbala was a principal investigator on a large U.S.-funded trial in Congo of the antiviral tecovirimat, which was used to treat mpox in high-income countries in 2022. Last week, the National Institute of Allergy and Infectious Diseases announced that the drug had not improved mpox resolution in Congolese patients with Clade 1 infections.

“As we see with tecovirimat, in different contexts the drug or the vaccine can act differently,” Mbala said. “We can’t be sure until we are able to test them.

The New York Times News Service