Monkeypox vaccination begins — can the global outbreaks be contained?

Monkeypox vaccination begins — can the global outbreaks be contained?


A man receives a vaccine at a monkeypox clinic in Montreal, Canada, on 6 June.Credit: Christinne Muschi/Reuters

As global monkeypox cases continue to rise, public-health officials and researchers are questioning whether the current outbreaks can be contained. The World Health Organization has said that the situation is unlikely to escalate into a full-blown pandemic. But more than 1,000 people have now been confirmed to have been infected with the virus in nearly 30 countries where outbreaks do not usually occur (see ‘Unusual spread’).

Countries including Canada, the United Kingdom and the United States have begun implementing a strategy called ‘ring vaccination’ to try to halt the spread of the virus. This involves administering smallpox vaccines — which are thought to be effective against monkeypox because the viruses are related — to people who are known to have been exposed through close contact with an infected person.

But there are unknowns and challenges that come with using this strategy for monkeypox, says Natalie Dean, a biostatistician at Emory University in Atlanta, Georgia. Although the vaccines are considered to be safe and effective for use in people with smallpox infection, the vaccines have had limited testing against monkeypox. The strategy also relies on highly rigorous contact tracing, which might not be implemented in every country, and people must also agree to be inoculated with vaccines that can carry rare, but serious, side effects.

Ring vaccination can be a powerful tool, Dean says, but to be effective it needs to be used early — while case numbers are still manageable. “As the numbers crop up and you think about the number of contacts each individual has, the logistics just become more complicated,” she says, adding that there is a narrowing window of opportunity to prevent the virus from gaining a more permanent foothold in human or animal populations in countries where the global outbreaks are occurring.

These concerns were further heightened on 3 June, when the US Centers for Disease Control and Prevention (CDC) reported genomic data showing that there are two distinct strains of the monkeypox virus responsible for the outbreaks. This finding could suggest that the virus has been circulating internationally for longer than expected. But Andrea McCollum, an epidemiologist who heads the poxvirus team at the CDC, says that while new genomic data doesn’t change the agency’s efforts to contain the virus, it will complicate the investigation into the outbreaks’ origins.

Smallpox stockpiles

Some countries maintain stockpiles of smallpox vaccines, mainly because public-health officials have been worried that smallpox — a disease eradicated more than 40 years ago that can kill about 30% of people infected — could still be accidentally released from laboratories where samples are kept, or could be weaponized. Two main types of smallpox vaccines are available today, each containing a live poxvirus, called vaccinia, that is closely related to smallpox. So-called second-generation vaccines can cause rare, but serious, side effects because they contain vaccinia capable of replicating in a person’s cells. Third-generation versions have fewer side effects because they contain a weakened virus that can’t replicate.

These smallpox vaccines are thought to be about 85% effective against monkeypox infection, according to the CDC and the WHO, which both cite “past data from Africa”, where outbreaks have occurred for decades, to support their assessments. But the highly-cited figure is “shaky”, Dean cautions.

It comes from a 1988 observational study1 carried out in Zaire (now the Democratic Republic of the Congo) that studied 245 people infected with monkeypox and 2,278 of their contacts, according to McCollum. Because the second- and third-generation smallpox vaccines produce a comparable antibody response in people compared with the now-obsolete first-generation vaccines administered in the study, scientists think the newer vaccines would have a similar efficacy against monkeypox. There is also compelling evidence from animal studies that they would work against monkeypox, but they haven’t been directly tested against that disease in people, Dean says.

Unlike how countries responded to COVID-19, public-health officials aren’t currently mulling a mass-vaccination campaign for monkeypox. That’s because the side effects of the second-generation smallpox vaccines, which have been stockpiled by countries at a much higher level than third-generation versions, prevent them from being given to children, individuals who are pregnant, those who are immunocompromised or those with a spectrum of skin conditions that fall under the classification of ‘eczema’. Third-generation vaccines, which fewer countries have access to, have fewer side effects and could therefore be given to a greater proportion of people.

At the moment, the risk posed by monkeypox to the general public isn’t high enough to warrant mass-vaccination, given the side effects and availability issues, says Daniel Bausch, the director of emerging threats and global health security at the Foundation for Innovative New Diagnostics in Geneva, Switzerland. But if the virus starts spreading in vulnerable populations such as pregnant people or children, or if it turns out to have a higher fatality rate than expected, that risk-benefit calculation could change.

No deaths from monkeypox have been reported outside Africa so far this year; however, 4.7% of people who have contracted monkeypox across seven countries in West and Central Africa in 2022 have died. This makes the discussion of a ring — or even broader — vaccination campaign in non-African nations sting for researchers in Africa who have been fighting monkeypox outbreaks for decades, says Ifedayo Adetifa, the head of the Nigeria Centre for Disease Control in Abuja. WHO member nations have pledged more than 31 million smallpox vaccine doses to the agency for use in smallpox emergencies, yet these doses have never been used against monkeypox in Africa.

Limited data

Usually, monkeypox causes fever, swollen lymph nodes and sometimes-painful fluid-filled lesions that form on a person’s skin. Left untreated, the infection can clear in a few weeks — especially for those with access to health care.

Bavarian Nordic, a biotechnology firm based in Hellerup, Denmark, that created the third-generation smallpox vaccine MVA-BN, said on 30 May that it has been taking orders in response to global demand. If countries had a larger stockpile of third-generation smallpox vaccines, Raina MacIntyre, an infectious-diseases epidemiologist at the University of New South Wales in Sydney, Australia, says it would be a “no-brainer” to use them for a robust ring vaccination campaign against monkeypox.

So far, the United States has been offering either a second- or third-generation smallpox vaccine regimen to people at “high” or “intermediate” exposure risk, which the CDC defines as a person who had “unprotected contact” with the skin or bodily fluids of a person with monkeypox, or who was within 6 feet (1.8 metres) of an infected person. Smallpox vaccines are thought to protect against monkeypox infection if administered within four days of exposure, according to the CDC.

But there is limited real-world data to support this guidance. Although the second-generation vaccine stockpiled in the United States is meant to be administered as a single dose, MVA-BN is a two-dose vaccine, administered with 28 days between shots. Because of a lack of testing against monkeypox in humans, it is unknown whether a single dose of MVA-BN would be enough to stop an infection, even if given within four days of exposure, McCollum says.

Challenges ahead

Even if more nations procure smallpox vaccines and begin a ring vaccination campaign, there is a large difference between theory and reality when it comes to implementing the strategy, MacIntyre warns. In theory, monkeypox is conducive to a ring vaccination approach because it spreads slowly relative to most human viruses and has a long incubation period. But in reality, a successful ring vaccination campaign relies on robust testing and contact-tracing infrastructure, as well as the ability to quickly vaccinate any high-risk contacts, she says.

And getting people to take vaccines could be difficult. As of 24 May, only 15 of 107 community contacts and 169 of 245 healthcare workers in the United Kingdom opted to take an MVA-BN vaccine after possible monkeypox exposure during the current outbreaks, according to a report in Eurosurveillance2.

To avoid tensions and misinformation, health officials will have to communicate very clearly to the public why the campaign is necessary and why only select individuals are receiving vaccines, says Bausch, who has worked for the WHO and the UK government to address Ebola outbreaks. Another worry is the stigma building up around the current monkeypox outbreaks: many of the cases have been in men who have sex with men. Bausch says that if the disease continues to be stigmatized, people might not want to comply with contact-tracing efforts, which would make ring vaccination much harder.

To stop the spread of the virus, health officials will probably need to look beyond vaccination and focus on quarantine and isolation, as well as community education, he adds. As Bausch wrote in a 2021 comment in Nature Medicine3, although ring vaccination has had its successes, “it is far from a panacea”.

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