Why a lack of monkeypox vaccine could threaten the immunocompromised

Why a lack of monkeypox vaccine could threaten the immunocompromised

The shortage of monkeypox vaccine doses in the United States, which is expected to last for several months, raises pressing questions about how well and for how long a single shot can protect against the virus.

The vaccine, called Jynneos, is approved as a two-dose regimen, but most people at risk of infection have received one dose – if they can find it. Now, the shortage has led federal officials to consider a rarely used approach: a so-called dose-saving strategy, which provides shots that each contain only one-fifth of a single dose.

For most recipients, one shot should be enough to ward off severe disease, and there is some evidence that even smaller doses can be effective. But preliminary research suggests that people with HIV or other conditions that weaken the immune system may be less protected than people without such diseases, according to some experts.

“One dose is better than none,” said Dr. Alexandra Yonts, an infectious disease physician at Children’s National Hospital in Washington, DC. But people with “HIV and other immunocompromised individuals need to be aware that they may not have an adequate level of protection from infection, even with vaccination,” she added.

Even two weeks after the shot, when the antibody response is underway, immunocompromised people may still need to “use all other precautions to avoid exposure, according to public health guidance,” she said.

The findings also suggest that some men should be prioritized for full vaccination. Given the supply constraints, it can be difficult.

Federal officials have ordered nearly seven million doses of Jynneos, but the shots won’t arrive for months. So far, the Biden administration has sent about 600,000 doses to states. It said last week that 800,000 extra doses had been allocated to states, but distribution could take weeks.

Faced with shortages, some cities, including Washington and New York, are limiting other doses to stretch supplies. Officials at the Food and Drug Administration and the CDC have disagreed with that strategy, noting that Jynneos is approved as a vaccine to be given in two doses 28 days apart.

But as federal health officials declared a public health emergency on Thursday, Dr. Robert Califf, the commissioner of the FDA, said the agency is now considering approving shots that contain just one-fifth the usual dose, given between the layers of the skin instead. off under it.

The FDA must grant Jynneos emergency use approval for it to be administered in this manner.

The dose-saving approach has been used when supplies of other vaccines are scarce. But giving intradermal shots requires more skill than is needed for more traditional vaccinations.

One shot is probably enough to prevent severe symptoms in most people, and the dose-saving strategy can work just as well. But it’s unclear whether a scaled-down diet is enough to prevent infection, and if so, how long that immunity might last, federal health officials said.

“We’re in a data-free zone,” said Dr. Emily Erbelding, an infectious disease expert at the National Institutes of Health, who oversaw testing of Covid vaccines in special populations.

An often quoted statistic states that the vaccine is 85 percent effective against monkeypox. These data do not come from trials with Jynneos, but from a small study from 1988 that looked at the incidence of monkeypox among people who had been inoculated for smallpox earlier in life.

No large clinical trials of Jynneos as a monkeypox vaccine were conducted in humans before it was approved. Instead, the FDA relied on measurements of antibody responses in small groups of people after immunization with Jynneos compared to those produced by ACAM2000, an earlier smallpox vaccine.

In studies led by the manufacturer, Bavarian Nordic, two doses of Jynneos produced antibody levels in humans that were about the same as after one shot of ACAM2000.

Antibody levels after the first shot of Jynneos first rose for two weeks and then remained flat until the second dose four weeks later, when they rose to very high levels – higher than those recorded with ACAM2000.

Researchers read that means that if the first dose is not followed by a second, the protection may not be long-lasting.

“Ideally, a second dose would be administered if protection for more than the four-week period is desired,” said Dr. Yonts, who reviewed the data for the FDA as a staff scientist.

She added that it may be reasonable to delay the second dose until eight weeks. “But if it’s going to take six months, then I think the priority will lean more towards those who are more severely immunocompromised,” she said.

Injecting one-fifth of a regular dose of Jynneos between layers of skin, as the FDA proposed on Thursday, may be effective, according to limited research. The skin has many more of the immune cells that respond to vaccines.

But the research is very limited. Researchers at the NIH had planned to test the dose-saving strategy in a clinical trial that would begin in a few weeks. It is unclear whether these plans will be shelved or accelerated.

Information about how Jynneos performs in people with HIV, especially in those with severe immune problems, was already sparse. In a study conducted by Bavarian Nordic, the antibody response to vaccination tended to be reduced: 28 days after the first shot, 67 percent of those with HIV produced antibodies, compared to 84 percent of those uninfected.

While Dr. Yonts said the data from that study was inconclusive, reduced antibody responses are often seen among immunocompromised people who receive other vaccines. For example, while evaluating Covid vaccines, researchers found that patients with HIV were more likely to have breakthrough infections.

“Individuals with severe or moderate immunosuppression are recommended for additional doses of common vaccines,” said Keri Althoff, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, who led the Covid vaccine study. “As immunosuppression increases, the response to the vaccines decreases.”

The CDC and the New York City Department of Health say Jynneos is safe for people with HIV, but the agencies have not addressed its effectiveness in that population.

In contrast, health authorities in the UK say that for people who “are HIV positive or have another condition or treatment that leads to a weakened immune system, the vaccine may not protect you as well”.

The vaccine’s package insert also notes that immunocompromised individuals “may have a reduced immune response.”

“Two shots can be very important in this population, which actually doesn’t happen in the public health response,” said Dr. Chloe Orkin, an infectious disease physician at Queen Mary University of London, referring to immunocompromised people.

But until more doses are available, state and local health departments may have little choice but to stick with scaled-down regimens.

“In an environment of scarcity, we must do everything we can to get the benefits of the vaccine to the city as quickly as possible,” Patrick Gallahue, a spokesman for the New York City Health Department, said in a statement.

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