How the smallpox vaccine stockpile could stop monkeypox in its tracks

The world’s stockpiling of vaccines against a now-extinct threat means we have the tools to stop monkeypox – but we need a coordinated and concerted effort.

Monkeypox virus in vitro in laboratory


Unusual outbreaks of monkeypox across Europe, Canada, the USA and Australia – where it is not normally endemic – have raised the possibility of using stockpiles of smallpox vaccine to prevent it.

Monkeypox – which causes a fever and rash all over the body – is closely related to smallpox, a disease that was declared eradicated in 1980. As the antibodies produced are cross-reactive, smallpox vaccines can be highly – 85% – effective in preventing monkeypox. 

“We have a chance to shut down this virus and not allow it to become endemic in more countries. To remind people that you're not just getting vaccinated for yourself, but to protect other people. And to point out that if we had quashed COVID-19 back in January of 2020, we wouldn’t have lost a lot of lives.”

There have so far been nearly 100 cases across 12 countries that are not endemic for monkeypox, according to the World Health Organization. However, there have been more than 1,200 cases since January in the Democratic Republic of the Congo, where monkeypox is endemic, with 58 deaths.

Rapid action to contain it

Until now, most outbreaks of monkeypox outside of Central and Western Africa, where it is endemic, have tended to burn out on their own.

However, now that there are several outbreaks simultaneously in non-endemic areas too, we need “rapid, concerted action to contain it” says Dr Lee Hampton, a  medical epidemiologist at Gavi.

Shutting down transmission, says Dr Hampton, will require “a real effort to trace contacts of people who have monkeypox, and then isolate and quarantine them if necessary, and then ideally also use things like ring vaccination with smallpox vaccine (as has been used to contain Ebola). With those steps, we could very likely bring it under control.” 

The fact that it has spread to so many countries already suggests that “it’s not just going to die off on its own”, he adds. Routine smallpox vaccination was stopped decades ago, so many of us have no immunity to monkeypox or smallpox.

Lessons learned from Ebola

Pre-COVID-19, Ebola dominated headlines as one of the most worrying infectious disease threats. During the 2014 to 2016 outbreak in Guinea, Liberia and Sierra Leone in West Africa, 11,300 people died, though this number is thought to have been vastly underestimated.

In order to contain this threat and stop it from spreading to the rest of the world, agencies such as the World Health Organization (WHO) and others, with support from Gavi, mounted an aggressive response that involved carefully tracing contacts and quarantining those infected.

In addition, this was a population who relatively rarely undertook international travel – though containing the spread of Ebola in Nigeria following its introduction by an individual who flew to Nigeria from Liberia required an extraordinary effort. If Ebola had spread among a population with extensive, frequent global travel, that outbreak could have been even more lethal.

The meticulousness required by entire teams of epidemiologists, community workers, government officials and the global health community to control Ebola in West Africa was not cheap either – the US alone spent US$ 2.4 billion in Ebola response.

This was deemed necessary in order to prevent global catastrophe. And similar meticulousness is what may be required to bring this international monkeypox outbreak under control, although doing so now, before monkeypox has become more widespread, should be considerably less expensive than with Ebola in 2014 to 2016.

Smallpox vaccine stockpiles

There are currently four smallpox vaccines:

  • the original calf lymph vaccinia virus that was used to eradicate smallpox,
  • ACAM2000, a newer version of the vaccinia live vaccine,
  •  Jynneous, a live, non-replicating vaccine (approved by the FDA in 2019 against smallpox and monkeypox),
  •  Aventis Pasteur Smallpox Vaccine (APSV) an investigational replication-competent vaccine that could be authorised for use in an emergency.

The WHO stockpile consists of leftover vaccine from the smallpox eradication effort (the calf lymph vaccinia vaccine), and 31.01 million doses of smallpox vaccine pledged by France, Germany, New Zealand, the UK and the US.

Since the countries with stockpiles are high-income countries, will this mean we’ll see more vaccine inequity, as we have seen for COVID-19 and many vaccines before that?

“Nothing is predetermined,” says Dr Hampton, however unlike with COVID-19, we are not trying to produce a supply of a vaccine that was rapidly being outstripped by the enormous demand.

“The US has enough doses for the entire population, for example, and this could be enough to share with other countries in targeted strikes against monkeypox. However, regulatory issues may be complicated for vaccines that are not used in the general population on a routine basis.”

Scaling up smallpox vaccine production would mean growing more vaccinia virus, even for the non-replicating vaccine, which would take time, says Dr Hampton, so the best course of action for now would be to use the existing stockpiled vaccines to halt outbreaks. 

Risky but necessary

It’s important to acknowledge that there are risks with using a live virus vaccine, even though they are incredibly effective. In such vaccines, as happens with the poliovirus vaccine, there is a small chance of spreading disease (in this case cowpox) from a person who has been vaccinated to one who hasn’t. The replicating vaccinia vaccines are also risky for immunocompromised people, such as those with HIV/AIDS.

However, while there have been no deaths from the cases in the West so far, monkeypox is much more fatal in children. If these outbreaks go unchecked, we could start seeing deaths in children, says Dr Hampton.

“We have a chance to shut down this virus and not allow it to become endemic in more countries. To remind people that you’re not just getting vaccinated for yourself, but to protect other people. And to point out that if we had quashed COVID-19 back in January of 2020, we wouldn’t have lost a lot of lives,” he adds.