The shortage of monkeypox vaccine doses in the United States, which is expected to last for 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 a dose — if they can find it. Now the shortage has prompted federal officials to consider a rarely used approach: a so-called dose-sparing strategy, in which shots are fired that each contain just one-fifth of a single dose.
For most recipients, one injection should be enough to stave off a serious illness, and there’s evidence that even smaller doses can be effective. But preliminary research suggests that people with HIV or other diseases that weaken the immune system may be less protected than people who don’t have 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, from infection, even with vaccination,” she added.
Even two weeks after the shot, if the antibody response is underway, immunocompromised people may still need to “take every other precaution to avoid exposure as per public health guidelines,” she said.
The results also suggest that some men should be prioritized for full vaccination. In view of the supply bottlenecks, this is likely to be difficult.
Federal officials have ordered nearly seven million doses of Jynneos, but the syringes won’t arrive for months. So far, the Biden administration has shipped about 600,000 cans to states. Last week it said states would be allocated 800,000 additional doses, but distribution could take weeks.
Faced with shortages, some cities, including Washington and New York, are cutting second doses to expand their supplies. Officials at the Food and Drug Administration and the CDC disagreed with this 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 approving shots that contain only one-fifth the regular dose and are instead administered between layers of skin from underneath.
What you should know about Monkeypox virus
What is monkeypox? Monkeypox is a virus similar to smallpox, but the symptoms are less severe. It was discovered in 1958 after outbreaks occurred in monkeys kept for research. The virus has been found mostly in parts of central and west Africa, but in recent weeks it has spread to dozens of countries and infected tens of thousands of people, mostly men who have sex with men. On July 23, the World Health Organization declared monkeypox a global health emergency.
The FDA would need to give Jynneos an emergency use authorization for it to be administered this way.
The dose-sparing approach has been used when supplies of other vaccines are scarce. But administering intradermal injections requires more skill than is required for more traditional immunizations.
One injection is probably enough to forestall severe symptoms in most people, and the dose-sparing strategy can work just as well. But it’s unclear whether a reduced regimen is enough to prevent infection, and if so, how long that immunity can last, federal health officials said.
“We are 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-cited statistic states that the vaccine is 85 percent effective against monkeypox. These data are not from Jynneos studies, but from a small 1988 study that looked at the occurrence of monkeypox in people who had been vaccinated against smallpox earlier in life.
No major human clinical trial of Jynneos as a monkeypox vaccine was conducted prior to its approval. Instead, the FDA relied on measurements of antibody responses in small groups of people after immunization with Jynneos compared to those produced by ACAM2000, a previous smallpox vaccine.
In studies led by its manufacturer, Bavarian Nordic, two doses of Jynneos in humans produced antibody levels roughly equivalent to those seen after an injection of ACAM2000.
Antibody levels after the first injection of Jynneos initially rose for two weeks and then remained stable until the second dose four weeks later, when they rose to very high levels – higher than those measured with ACAM2000.
Scientists interpret this to mean that protection may not last long if the first dose is not followed by a second.
“Ideally, a second dose would be administered if protection is desired for more than this four-week period,” said Dr. Yonts, who was a research associate reviewing the data for the FDA.
She added that delaying the second dose to eight weeks might make sense. “But if it’s going to be like six months, then I think the prioritization would lean more towards those who are more immunocompromised,” she said.
Injecting one-fifth of a regular dose of Jynneos between layers of skin, as the FDA suggested Thursday, may be effective, according to limited research. The skin has many more immune cells that respond to vaccines.
But the research is very limited. Scientists at the NIH had planned to test the dose-saving strategy in a clinical trial that is expected to start in a few weeks. It’s unclear if those plans will be put on hold or accelerated.
Information on how Jynneos works in people living with HIV, particularly those with severe immune problems, was already sparse. In a study conducted by Bavarian Nordic, the antibody response to vaccination tended to be lower: 28 days after the first vaccination, 67 percent of HIV-infected people produced antibodies compared to 84 percent of uninfected people.
while dr Yonts said the data from this study is not conclusive, a reduced antibody response is commonly seen in immunocompromised people who receive other vaccines. For example, when evaluating Covid vaccines, researchers found that patients with HIV were more likely to have had breakthrough infections.
“Additional doses of commonly used vaccines are recommended for individuals with severe or moderate immunosuppression,” 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 and Human Services say Jynneos is safe for people living with HIV, but authorities 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 another condition or treatment that leads to a weakened immune system, the vaccine may not protect you as well”.
The vaccine package insert also notes that immunocompromised people “may have a reduced immune response.”
“Two shots can be very important in this population, which doesn’t really happen in the public health response,” said Dr. Chloe Orkin, an infectious diseases doctor at Queen Mary University of London, referring to immunocompromised people.
But until more doses are available, state and local health officials may have no choice but to stick to reduced regimes.
“In an environment of scarcity, we must do everything we can to bring the benefits of the vaccine to the city as quickly as possible,” Patrick Gallahue, a spokesman for the New York City Department of Health, said in a statement.