When Covid-19 struck, humanity faced an out-of-control outbreak without vaccines or therapies. If it were a knife fight, we brought a crayon. 

The level of preparedness for monkeypox couldn’t be more different.

“We have vaccines squirreled away by our government,” said Blossom Damania, a professor of microbiology and immunology at the University of North Carolina School of Medicine. “I don’t think people need to be alarmed. Monkeypox is a serious disease. We need to respect it and take it seriously, but we don’t need to panic.”

The U.S. keeps two vaccines for smallpox approved by the Food and Drug Administration in the Strategic National Stockpile — a product, in part, of a 9/11-enhanced fear of bioterrorism. The monkeypox virus is similar enough that researchers expect both shots to offer protection, although only one, called Jynneos, has been FDA-approved for use against monkeypox. 

Officials from the Centers for Disease Control and Prevention said Monday that more than 1,000 doses of the Jynneos vaccine are stockpiled and can be distributed to those who have been in contact with infected people. In total, the government has more than 100 million doses of a smallpox vaccine called ACAM2000, CDC officials said.

May 23, 202206:03

In addition, the FDA has also approved two therapeutics to treat smallpox, called TPOXX and Tembexa. 

“The drugs that have been approved for smallpox have not yet been approved for monkeypox. But there’s excellent data in the filings for the licensure of those drugs where they’ve been tested against monkeypox in monkeys, and it works very well,” said Grant McFadden, the director of the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University. 

The national stockpile includes TPOXX doses, according to the FDA.  

“Containing an outbreak of monkeypox should be far less challenging than Covid-19,” said Dr. Peter Hotez, the dean of the National School of Tropical Medicine at Baylor College of Medicine and a co-director of the Center for Vaccine Development at Texas Children’s Hospital. “We already have interventions.”

Smallpox spurred humanity’s earliest vaccines

The strain of monkeypox that has been reported in the U.S. and Europe has had a 1 percent fatality rate in the past, according to the World Health Organization. By contrast, smallpox’s deadliest form killed about 30 percent of those who contracted it. So it’s unsurprising that smallpox spurred some of the earliest vaccination practices in human history.

Researchers think that people in Asia centuries ago inhaled dried pustules of smallpox to induce mostly mild infections, thereby inoculating them against severe illness. The practice — called variolation — spread, taking hold in England in the early 1700s. 

At the end of the 18th century, Edward Jenner, a British physician, began to develop the world’s first vaccine after he observed immune protection among people who’d contracted cowpox before they were exposed to smallpox. His vaccine used cowpox to induce smallpox immunity.

Later, safer smallpox vaccines that relied on other poxviruses were developed. After a global campaign, the WHO in 1980 declared that smallpox had been eradicated — a triumph of public health. 

But fears that the virus could re-emerge because of a laboratory accident or bio-attack have remained. The terrorist attacks of Sept. 11, 2001, worsened the concerns, thrusting the virus back into U.S. minds and the national budget. 

“There was a lot of concern about smallpox bioweapons attack, especially after the anthrax attacks in 2000,” Hotez said. “It was known the USSR had been working on weaponized smallpox for years.”

Since the turn of the millennium, the U.S. government has spent more than $1 billion to develop and stockpile the Jynneos smallpox vaccine. 

“The government have more than a million doses of Jynneos, liquid frozen, at the Strategic National Stockpile or stored in our facility in Europe,” said Paul Chaplin, the president and CEO of Bavarian Nordic, the Danish company that manufactures the vaccine. 

Just last week, Bavarian Nordic announced that the U.S. government had exercised its contract option to fill and finish 13 million more doses of freeze-dried Jynneos vaccine in the coming years. But the announcement wasn’t related to the recent outbreak, Chaplin said: “It was completely coincidental.” 

Jynneos is made from a modified, nonreplicating form of the vaccinia virus, which is part of the same family as monkeypox and smallpox. 

ACAM2000, which is manufactured by Emergent BioSolutions, relies on a live vaccinia virus that can replicate. But it brings a risk of side effects, especially for people with eczema or conditions that suppress their immune system. So Jynneos’ nonreplicating formulation could offer a safer option for those at heightened risk of vaccine-related complications. 

Monkeypox isn’t likely to mutate like the coronavirus

Monkeypox isn’t as contagious as smallpox, and it causes less severe disease. 

“It’s much less pathogenic,” said Luis Sigal, a professor of microbiology and immunology at Thomas Jefferson University in Philadelphia who studies poxviruses. 

From a genetic perspective, however, the two viruses are similar. 

“Poxviruses are very highly conserved,” Sigal said. “In general, they have very little variation.” 

That’s why smallpox vaccines protect against monkeypox. 

“You can vaccinate with one and get protection from another, and it’s very long-lasting protection,” Sigal said. 

Dr. Rosamund Lewis, the head of the WHO’s Smallpox Secretariat, said past research has shown that the smallpox vaccines used decades ago “were protective against monkeypox about 85 percent of the time.”

“We now have new vaccines because, although smallpox was eradicated, research has continued for the last 40 years,” she added.

‘I think you can stop this pretty quickly’

Unlike the coronavirus, monkeypox is associated with a telltale rash that should make contact-tracing efforts easier.

In addition, the monkeypox virus doesn’t mutate rapidly like a coronavirus. Coronaviruses are encoded in RNA, while poxviruses are DNA viruses. When DNA viruses replicate, they have more sophisticated proofreading components. 

“DNA viruses are more stable,” said Damania of the University of North Carolina. “We’re not going to see all these variants coming out.” 

But, she added, the fact that the public stopped getting smallpox vaccines decades ago means more people are now susceptible to monkeypox. That could be a factor in the recent outbreaks

“It’s never happened where we have so many countries at the same time reporting outbreaks,” Damania said. 

To quell the new monkeypox outbreaks, public health leaders are likely to look to the past. Smallpox was controlled through mass vaccination and with a so-called ring strategy, in which people who were contacts of those with smallpox got vaccines. 

“That can be done again with monkeypox,” said David Evans, a virologist at the University of Alberta. “As long as the public health people jump on this and get out there and track down everyone these people have been in contact with, I think you can stop this pretty quickly.”

Monkeypox is unlikely to be snuffed out entirely, however, because it can spread among rodents and occasionally spill over into humans who interact with animals. 

“The advantage of smallpox, it’s one of the few viruses with so much specificity for humans. There was no animal reservoir. Once the last person got sick, there was nowhere to get the virus again,” Sigal said. “You cannot vaccinate the rodents.”


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