Why a shortage of monkeypox vaccines could pose a threat to the immunocompromised?

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

The vaccine, called Jynneos, is approved as a two-dose regimen, but most people at risk for infection have been given 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 involves giving injections each containing only one-fifth of a single dose.

For most recipients, one injection should be enough to ward off serious illness, and there’s some evidence that even smaller doses may be effective. But preliminary research suggests that people with HIV or other conditions that weaken the immune system may be less protected than people who don’t have such illnesses, according to some experts.

“One dose is better than none,” says Dr. Alexandra Yonts, an infectious disease physician at Children’s National Hospital in Washington, DC. of infection, even with vaccination,” she added.

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

The findings also suggest that some men should be prioritized for full vaccination. This can be difficult given the supply constraints.

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

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

But when federal health officials declared a public health emergency on Thursday, Dr. FDA commissioner Robert Califf said the agency is now considering allowing injections that contain only one-fifth the normal dose, instead, between the layers of skin. from below.

The FDA should grant Jynneos an emergency use authorization to administer it in this manner.

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

One injection is probably enough to prevent severe symptoms in most people, and the dose-saving strategy may work just as well. But it’s unclear whether a scaled back regimen is enough to prevent infection, and if so, how long that immunity can 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 oft-cited statistic says the vaccine is 85 percent effective against monkey pox. That data comes not from trials with Jynneos, but from a small 1988 study that looked at the incidence of monkeypox in people who had been vaccinated against smallpox earlier in their lives.

There was no major clinical trial of Jynneos as a monkeypox vaccine 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 vaccine against smallpox.

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

Antibody levels after the first injection of Jynneos initially 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.

Scientists read 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 that four-week period is desired,” said Dr. Yonts, who reviewed the data for the FDA as a staff scientist.

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

Injecting one-fifth of a normal dose of Jynneos between layers of skin, as the FDA suggested 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. Scientists at the NIH planned to test the dose-saving strategy in a clinical trial that was due to begin in a few weeks. It’s unclear whether those plans will be shelved or accelerated.

Information on how Jynneos performs in people with HIV, especially those with severe immune problems, was already scarce. In one study conducted by Bavarian Nordic, the antibody response to vaccination was mostly diminished: 28 days after the first injection, 67 percent of those with HIV produced antibodies, compared with 84 percent of uninfected people.

Although Dr. Yonts said the data from that trial was inconclusive, a decreased antibody response is often seen in immunocompromised people who received other vaccines. For example, when 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 immune suppression 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 agencies have not addressed its effectiveness in that population.

By contrast, health officials in Britain say that for people who are “HIV positive or have any other condition or treatment that leads to a weakened immune system, the vaccine may not protect you as well.”

The vaccine package insert also states that immunocompromised people “may have a diminished immune response.”

“Two injections could be very important in this population, which isn’t really happening 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 not have much choice but to stick with scaled back 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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