The mystery virus that protects against monkeypox

The other vaccine, ACAM2000, is a less-favoured option in the current monkeypox outbreak. First developed in the early 2000s as an alternative to the vaccinia strains used to eradicate smallpox, it has been stockpiled by several countries around the globe, including the US and the UK, for emergencies, such as a smallpox attack by terrorists.

There are recent reports of ACAM2000 being used against monkeypox, but it’s not yet licensed for this. Though it is safe in the vast majority of people, it does carry some risks – it can make copies of itself in the human body, so it’s not suitable for those who are immunocompromised.

As of July 2022, the US government had ordered nearly seven million doses of both smallpox vaccines to arrive over the next year, and there is now a global shortage. The irony is, it’s thought that the monkeypox outbreak may have only been possible because we ceased smallpox vaccinations in the first place.

“What we see now with monkeypox is very interesting,” says Esparza. “Smallpox was declared eradicated in 1980. And since then, smallpox vaccination has stopped in most countries, and immunity in the population against all Orthopox[viruses] has decreased. And that’s what is probably behind the emergence of monkeypox in the world.”   

Other viruses might be seizing the same opportunity. Though cowpox – the real deal this time, not the mistaken-identity version used in vaccines – is now rare in cattle, it’s still endemic in rodents throughout the globe. And since mass smallpox vaccination ceased in the early 1970s, more and more cases are being reported in children.  

Today people are most likely to catch cowpox from rats, or cats who pick it up from rodents in the wild – in one unusual case, it was acquired from a circus elephant. Most infections are mild, producing pox lesions on the hands or face, and unlike monkeypox they aren’t yet being spread from person-to-person.

But there have been fatalities. And as with monkeypox, the rise in cases has been linked to the end of widespread smallpox vaccination. Some experts have even gone so far as to describe cowpox as an emerging health threat.

So, vaccinia is still very much in demand. But will we ever know where humanity’s favourite poxvirus came from? Esparza is sceptical. “We still have more questions than answers,” he says, though he hints that he and his colleagues have made some progress – and will be releasing more tantalising details about the mystery in the coming months.

Whatever it’s made from, without the smallpox vaccine, there’s little doubt that the world would be a radically different place – still grappling with an ancient plague that had been disfiguring and killing people for millennia. And just as in the early 19th Century, we have far more to fear from avoiding inoculation, than we do from turning into human-cows…

Zaria Gorvett is a senior journalist for BBC Future and tweets @ZariaGorvett

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