Why a monkeypox vaccine shortage could threaten people with weakened immune systems

A 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 received one dose — if they could find one. Now, the shortage has prompted federal officials to consider a rarely used approach: the so-called dose-sparing strategy, which gives shots that each contain only one-fifth of the dose.

For most recipients, a single injection should be enough to prevent serious illness, and there is some evidence that even lower doses can be effective. But preliminary research suggests that some experts believe that people with HIV or other diseases that weaken the immune system may be less protected than people without such diseases.

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

Even two weeks after vaccination, when the antibody response begins, immunocompromised people may need to “use all other precautions to avoid exposure as recommended by public health,” she said.

The data also suggest that full vaccination should be preferred for some men. Given supply constraints, this 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 the states. It said last week that 800,000 additional doses were being allocated to states, but distribution could take several weeks.

Faced with shortages, some cities, including Washington and New York, are limiting second doses to increase their supplies. Food and Drug Administration and CDC officials disagreed 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. Robert Califf, the FDA commissioner, said the agency is now considering authorizing injections that contain only one-fifth of the usual dose, delivered between the layers of skin underneath. .

The FDA must grant Jynneos emergency use approval so that it can be administered in this manner.

A dose-saving approach has been used when supplies of other vaccines are in short supply. But intradermal injections require more skill than traditional immunization.

A single injection is probably enough to prevent severe symptoms in most people, and a dose-saving strategy may work just as well. But it’s not yet clear whether the reduced regimen 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 has overseen testing of Covid vaccines in special populations.

One oft-quoted statistic says that the vaccine is 85 percent effective against monkeypox. These data do not come from the Jynneos trials, but from a small study in 1988 that looked at the incidence of monkeypox among people who had been vaccinated against smallpox earlier in life.

No large clinical trials of Jynneos as a monkeypox vaccine were conducted in humans before its approval. Instead, the FDA relied on antibody response rates in small groups of people after immunization with Jynneos compared with ACAM2000, an earlier smallpox vaccine.

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

Antibody levels after the first injection of Jynneos initially rose for two weeks, then remained at the same level until the second dose four weeks later, when they soared to very high levels – higher than those recorded with ACAM2000.

Scientists have read that if the first dose is not followed by a second, the protection may not last long.

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

She added that delaying the second dose until eight weeks may be reasonable. “But if it’s about six months, then I think the priorities will lean more toward those who are more severely immunocompromised,” she said.

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

But research is very limited. NIH scientists planned to test the dose-saving strategy in clinical trials that will begin in a few weeks. It is not yet clear whether these plans will be delayed or accelerated.

Information about how Jynneos works in HIV-infected people, especially those with severe immune problems, has already been scarce. In one study by Bavarian Nordic, the antibody response to vaccination tended to decline: 28 days after the first vaccination, 67 percent of HIV-infected people developed antibodies, compared with 84 percent of uninfected people.

Although Dr. Younts said the data from this trial are not definitive, a decrease in antibody response is often seen in immunocompromised people who receive other vaccines. In an evaluation of Covid vaccines, for example, researchers found that patients with HIV were more likely to have breakthrough infections.

“Individuals with severe or moderate immunosuppression, additional doses of conventional vaccines are recommended,” said Carrie Altgoff, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health who led the Covid vaccine study. “As immunosuppression increases, the response to vaccines does decrease.”

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

In contrast, health officials in the UK say that for people who are “HIV positive or have any other condition or treatment that weakens the immune system, the vaccine may not protect you as well.”

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

“Two vaccinations can be very important for this population, which is not really happening in the public health response,” said Dr. Chloe Orkin, an infectious disease physician at Queen Mary University of London, referring to the immunocompromised.

But until more doses are available, state and local health departments may have no choice but to stick with reduced regimens.

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