Monkeypox Vaccines Are Too Gnarly for the Masses

In the past three years, the world has weathered two very different global outbreaks, caused by two very different pathogens, under two sets of very different circumstances. Unlike with the SARS-CoV-2 virus, with monkeypox, we’re entering an epidemic with highly effective vaccines—formulated to guard against smallpox—already in hand. Also unlike with SARS-CoV-2, with monkeypox, the shots stockpiled in U.S. stores are based on some pretty grody tech. Nearly all of the 100 million available smallpox vaccines are ACAM2000, an inoculation that, per FDA documentation, gets punctured “rapidly” into the arm via 15 jabs of a bifurcated, escargot-fork-esque needle, in a fashion “vigorous enough” to draw blood. In the weeks following, a gnarly, pus-laden lump blossoms, then scabs and falls away. “It’s oozy; it’s nasty; it definitely doesn’t feel good,” says Kelsey Cone, a virologist at ARUP Laboratories, in Utah, who received the vaccine about 12 years ago.

And unlike with SARS-CoV-2, with monkeypox, most of us won’t have to get those shots—or any smallpox vaccine at all, at least not anytime soon.

“Vaccination is not going to be the primary thing that squashes this outbreak,” says Boghuma Kabisen Titanji, a virologist and an infectious-disease physician at Emory University. Monkeypox is an older pathogen than the new coronavirus, with a richer history with humans; it spreads far less efficiently, and can more easily be snuffed out. And it will demand an almost opposite response—one that doesn’t require building widespread population immunity. Monkeypox, after all, is a different sort of emergency, in which the downsides of mass vaccination—for now—outweigh the perks. Our most abundant shot, ACAM2000, contains an active virus, related to smallpox, that can replicate inside human cells; “if you vaccinated a million people, you might result in more disease,” says Mark Slifka, a vaccinologist at Oregon Health & Science University, “than you would get from the monkeypox outbreak itself.”

If vaccinating everyone is off the table, that leaves us with blocking the outbreak upstream—with testing, education, and behavioral change, the exact tactics the U.S. has proved itself, time and time again, incapable of sustaining. As the world attempts to juggle two pathogens at once, we may find that monkeypox is, in some ways, an advanced version of a test we’ve taken before, and very recently flunked.

All that said, some of us will be nabbing smallpox shots, and sporting the subsequent scabs. Already, several countries in Europe and North America have kick-started what are called ring-vaccination campaigns—offering smallpox shots to close contacts of infected people. When supply is limited, this sort of targeted tactic “gives you the most bang for your buck,” Slifka told me, especially when a pathogen seems to be circulating in rather specific sectors of the population. A disproportionate fraction of the 1,600-plus monkeypox cases identified so far, across 35 countries, have been men who have sex with men, who likely caught the infection through intimate contact; health-care workers on the front lines of the outbreak, too, are being offered shots. Some jurisdictions are casting wider nets. Officials in Montreal, for instance, have started giving vaccines to men who have had at least two male sex partners in the past couple of weeks.

These tactics are a far cry from mass immunization—which demands an abundantly clear risk-benefit calculus. The shots for SARS-CoV-2 (and many other microbes in our past and present) have that: The virus spreads swiftly and often asymptomatically, and has killed millions around the world. It is difficult to control through most other means. And the vaccines scientists have cooked up to fight it are effective and supersafe. Monkeypox, however, is “nothing like” its coronaviral colleague, says Cone, who used to work with the poxvirus. Unlike airborne SARS-CoV-2, monkeypox passes between people mostly via sustained close contact, and seems to transmit “only during the symptomatic phase,” says Dimie Ogoina, a physician at Niger Delta University who has studied monkeypox. Amid the current outbreak, most cases detected outside West and Central Africa—where monkeypox is endemic, and not particularly concentrated among men who have sex with men—have been relatively mild.

And the vaccines available to combat monkeypox have real drawbacks that many other shots do not. Because ACAM2000 contains an active virus, it may be especially risky for infants or people who are pregnant, immunocompromised, or living with HIV. The shot also comes with a small but notable risk of heart inflammation, or myocarditis, and its documentation warns of other serious side effects, including blindness, spreading the vaccine virus to others, and even death. (Still, the jab is a big improvement over its direct predecessor, Dryvax—an inoculation that many Americans over the age of 50 have—which Slifka describes as pus “ladled out of a cow.”) “You would really have to make a compelling argument,” Titanji told me, “to convince me to use ACAM as the primary tool.”

A newer alternative, known as MVA (or Jynneos in the United States), built around a weaker version of the vaccine virus, is much safer. But the globe’s MVA stock is low, with most refills months away, and the vaccine has yet to be approved in Europe for use against monkeypox. Experts also lack solid intel on just how well both ACAM2000 and MVA actually work against monkeypox, because the virus—and the vaccinations that fight it—remains rare for most of the world.

Even ring vaccination has its limits. The strategy works best when cases can be rapidly identified, and close contacts, speedily traced, are enthusiastic about receiving the shots. Right now, monkeypox cases are not being detected and isolated quickly enough; infected people are likely still mingling with others who aren’t immune. The disease’s symptoms also have not been consistently manifesting as monkeypox’s normally telltale unfurling from fever and swollen lymph nodes to rashes and lesions. Stigma, too, has shrouded the infection, hurting efforts to halt it. And vaccines have been declined by some of the people at risk of exposure—even by health-care workers.

With vaccines cut from the headlining slot, our roster of remaining tools might be looking a touch meager. Already, the global response to the epidemic has been hamstrung by a lack of testing capacity and a sluggish behavioral response—one that experts worry is being further bogged down by understandable exhaustion after two-plus years of COVID, COVID, COVID. That inertia, if it continues, will likely cost us. This outbreak marks the first time that monkeypox has spread so steadfastly outside the regions of Africa where it’s typically found, and the virus has been slingshotting all sorts of surprises our way. “The pathogen is not new, but the way that it’s moving is new, and the way it’s presenting on people’s bodies is new,” says Keletso Makofane, a researcher at Harvard’s School of Public Health. Experts are still scrambling to get a firmer grip on the disease’s symptoms, which can be easy to confuse with those of STIs, and their severity. Some of them, including Makofane, are also working to scale up diagnostics, and map the networks that have allowed the poxvirus to spread. That knowledge will hopefully bolster efforts to root out cases and close contacts, get them into isolation and quarantine, and vaccinate the (for now) limited number of vulnerable people.

The success of those strategies depends, as it has with COVID, on collective action, flexibility, and trust. “Communication with the public is crucially important,” Makofane told me, especially in ways that won’t fuel discrimination or shame. People unfamiliar with the pathogen will need to grow savvy to its symptoms and ways of spreading; they’ll need clear pathways to care. Having behavioral advice at the ready could also boost efforts to dole out shots, not least because it’ll reduce the number of people who might need them.

But “people don’t like making changes to their behaviors,” says Saskia Popescu, an infection-prevention expert at George Mason University. They want one-stop solutions, which most microbes do not lend themselves to. But lean too heavily on shots right now—or worse, give the false impression that they’re the most important intervention here—and the world could fall into some of the same traps of “vaccine absolutism” that have dogged the COVID-19 discourse, Popescu warned. “I worry we’re so vaccine-focused that we’re going to repeat our [COVID] failures,” she told me, and let other measures fall to the wayside as public disillusionment grows.

Should the outbreak continue to balloon, so will vaccination’s role. If the virus keeps spreading and moving into new networks, a wider immunization campaign could become more pressing. Though most of this monkeypox outbreak hasn’t been severe, since the start of 2022, the virus has killed more than 70 people in West and Central Africa in 2022. And should the pathogen expand its domain, or seed itself into an animal reservoir, there’s no telling what it will bring next. The pathogen could happen upon mutations that help it spread faster, or cause more severe disease. “That’s my biggest concern,” says Rafi Ahmed, an immunologist at Emory University. “We’ve never seen deaths in high-income settings,” says Anne Rimoin, an epidemiologist and a monkeypox expert at UCLA. “But that doesn’t mean we won’t.” Unlike with SARS-CoV-2, with monkeypox, a near-best-case scenario is one in which smallpox vaccination rates remain rather low—because, having found other ways to halt the virus’s roll, we do not need them to rise.

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