Everything you need to know about the monkeypox vaccines

The global outbreak of monkeypox has so far led to more than 24,000 cases in over 80 countries, and the World Health Organization has warned that the window of opportunity to contain the disease and prevent it from becoming endemic outside Africa is rapidly closing. Vaccines represent a potentially crucial measure.

Monkeypox vaccines are already being deployed around the world, and news reports have described a scramble" as countries desperately try to secure some of the limited number of available doses. There are concerns that poorer nations will go without. At the same time, there's a lot we don't know about how effective the vaccines are even likely to be. We spoke to vaccine manufacturers, virologists, and epidemiologists to get answers to the most urgent questions.

What are the vaccines?

Three vaccines are being considered to tackle the current global outbreak. All three were developed as smallpox vaccines. Only one is licensed for monkeypox by the US Food and Drug Administration: a vaccine called MVA-BN, or Jynneos in the US.

Another of the vaccines, ACAM2000, is licensed by the FDA for smallpox but may be used for monkeypox with the submission of extra forms. The third vaccine being considered is LC16m8, which is licensed for smallpox in Japan.

Which vaccine is best?

The Jynneos vaccine is considered to be the safest, so it will most likely be the vaccine of choice in most regions, says Dorota Kmiec, research group leader at the Institute of Molecular Virology in Ulm, Germany. It contains a form of a virus related to smallpox, called vaccinia. The form of the virus in the vaccine is not able to replicate in the body, so it doesn't seem to be able to make people sick.

By contrast, ACAM2000 and LC16m8 both contain a form of the vaccinia virus that is able to replicate in the body to some degree. This means that they have the potential to make people unwell. These vaccines are not recommended for people who have, or live with others who have, weak immune systems.

The ACAM2000 vaccine is delivered via a needle that works by scratching the surface of the skin and creating a wound that takes weeks to heal. This wound eventually forms a scab and can shed virus, so it must be properly cared for. Jynneos, on the other hand, is delivered via an injection under the skin, in two doses, and doesn't form a scab.

Why are smallpox vaccines being considered for monkeypox?

Both smallpox and monkeypox are poxviruses. Poxviruses are similar, and historically, some have been used to protect people against more dangerous viruses in the same family.

Smallpox and monkeypox do have plenty in common. At the genetic level, the two viruses are 85% identical," says Jason Mercer, a pox virologist at the University of Birmingham. Both can cause a distinctive rash of pustules" on the skin, which eventually form scabs.

But there are key differences. Generally, monkeypox causes a less severe illness. While smallpox is thought to affect only humans, monkeypox can infect animals, which can act as reservoirs" from which the virus can pass to humans. Monkeypox is so named because it was first spotted in monkeys, but it usually infects rodents.

Countries no longer routinely vaccinate against smallpox. Is that why we're seeing a monkeypox outbreak now?

Possibly. Scientists speculate that the end of widespread smallpox vaccination in the 1970s may have contributed to today's outbreak.

Since smallpox vaccination was stopped, the frequency and size of monkeypox outbreaks in both endemic and non-endemic countries has increased every decade," says Mercer. [There is] a worldwide population of individuals under 50 years old that are susceptible to infection with poxviruses."

Will the smallpox vaccines protect against monkeypox?

They are expected to. If the end of mass smallpox vaccination has contributed to current monkeypox outbreaks, that suggests that smallpox vaccines of the past provided long-lasting protection against monkeypox, too.

Heinz Weidenthaler, vice president of clinical strategy at Bavarian Nordic, the company that makes the Jynneos vaccine, says he expects one dose to provide good protection that lasts for at least two years, based on the immune response to the vaccine observed in safety studies.

But no one can say for sure. Jynneos was developed after the eradication of smallpox. It has been tested against poxviruses, including monkeypox, in small numbers of mice, monkeys, and prairie dogs. But it has not been trialed in people who have, or are at risk for, monkeypox. Instead, the company has measured the immune response generated by the vaccine in healthy volunteers and compared it with the result for an older smallpox vaccine. Previous outbreaks of the disease have been too sporadic to conduct a controlled trial, says Weidenthaler. The only data we have on efficacy is from animal models," he says.

That is partly why the WHO is also recommending other protective measures. Last week, for the first time, the organization specifically recommended that men who have sex with men-who represent around 98% cases in this outbreak so far-limit their sexual partners.

Vaccination is one of the main tools we have to control the monkeypox outbreak, but it cannot be the only one," says Kmiec. Disease surveillance and rapid diagnosis will also be vital in identifying who should be vaccinated, and clear communication on the risks of exposure is also important, she says.

How effective are the vaccines likely to be?

The WHO website states that vaccination against smallpox was demonstrated through several observational studies to be about 85% effective in preventing monkeypox." This figure comes from research in the 1980s, when scientists investigated an outbreak of monkeypox in what is now the Democratic Republic of Congo.

The investigation focused on 147 people with monkeypox, who passed the infection to 47 of the 1,573 people they had been in close contact with. The attack rate," or chance of being infected, was 85% higher in those contacts who were unvaccinated, the team found.

The study was small, and it didn't set out to directly test the effectiveness of the vaccines. I think it's a bit stretched to come to that conclusion," says Weidenthaler. But it's all we have right now."

Kmiec points out that other studies report a lower incidence of monkeypox among people treated with smallpox vaccines, although they are not completely protected. An investigation into a monkeypox outbreak in the Democratic Republic of Congo in the mid-1990s found that 15% of 84 people with the disease had been previously vaccinated, for example.

Animal studies suggest that the vaccine offers 80 to 100%" protection against disease, says Weidenthaler. But we've simply had no opportunity to test this in humans."

What we need to do now is collect the evidence and use the vaccine now as a precautionary measure in countries that have decided to use it," says David Heymann, an infectious disease epidemiologist at the London School of Hygiene and Tropical Medicine, who has investigated monkeypox outbreaks.

Is there enough vaccine to go around?

According to the WHO, there are 16 million doses of the vaccine available globally.

Most of these doses are currently in bulk form; the formula for many doses is kept in a few containers at low temperatures, which allows it to be stored for long periods of time. The vaccine must go through a fill and finish" process that involves preparing individual vials for vaccination-a process the WHO says will take several months.

Given the limited global supply, some have already raised concerns about a scramble for doses and the potential for hoarding by wealthy nations, given past experiences with covid-19 vaccines. Bavarian Nordic currently has 250 liters of the vaccine formula, enough for around 15 million doses,says company representative Rolf Sass Sorensen. But it's all owned by the US," he says.

Bavarian Nordic was contracted to develop a safer smallpox vaccine for the US in the early 2000s, amid fears that smallpox could be used as a bioterrorism weapon against the country, says Sorensen. The company has produced and stored Jynneos for the country in the years since.

Sorensen denies there has been any bottleneck in the supply of the vaccine so far. The company has fulfilled every request it has received since the start of the outbreak, he said on July 28-which includes requests from every affected country.

We have not seen any requests so far that are exceeding our current capacity," says Sorensen. We have heard from multiple sources that there is a limitation, but we think it's a ghost really."

The ability to deliver these doses has, to a large extent, been down to luck, says Sorensen. When the outbreak came, we had ... really by coincidence, equivalent to 2 million doses in bulk of our own vaccine [in addition to that owned by the US], and that was converted into vials immediately," he says. And that was what we started to sell."

There are very few" of those doses left now, but the company has scaled up production," he adds.

Will stockpiled vaccines be shared?

Hopefully. In addition to the bulk vaccine stored by Bavarian Nordic, the US Strategic National Stockpile, an emergency store of medicines and medical supplies, includes millions of doses of ACAM2000 and thousands of doses of Jynneos.

More countries are thought to have stockpiles of smallpox vaccine. I don't think it's really known which countries have stockpiles and how much vaccine they have, but it's not only the US," says Heymann.

The WHO has called on nations that have the vaccine to share doses with those that don't. Some scientists have pointed out that the monkeypox vaccines have not been made available to the African countries where the virus is endemic.

I think we all have to be concerned about equitable access to vaccines," says Heymann. But he highlights the fact that these vaccines were developed for stockpiles to begin with. They were sold to countries for stockpiles in the event that smallpox would be used as a bioterrorist weapon," he says.

Without the drive to create vaccine stockpiles, we wouldn't have Jynneos. It's a real Catch-22, isn't it," says Hermann. It's a complicated issue. We need [incentives and financial support to make] these vaccines, but at the same time we need them to be shared as widely as possible."