The federal government just unveiled a new strategy to stretch its limited supply of monkeypox vaccine: injecting it in a way that requires less vaccine per person.
The Food and Drug Administration authorized the dose-splitting strategy Tuesday, which could vaccinate up to five times as many people against monkeypox using the country’s current supply of shots. Instead of delivering the vaccine just under the skin, as is currently done, providers would administer the vaccine into the skin, a procedure that a laboratory study suggests requires just one-fifth the amount of vaccine used in a standard, deeper shot that pierces the underlying fatty tissue.
“In recent weeks, the monkeypox virus has continued to spread at a rate that has made it clear our current vaccine supply will not meet the current demand,” said FDA Commissioner Robert Califf in a statement. “The FDA quickly explored other scientifically appropriate options to facilitate access to the vaccine for all impacted individuals. By increasing the number of available doses, more individuals who want to be vaccinated against monkeypox will now have the opportunity to do so.”
Intradermal vaccination, as it’s called, could drastically expand the United States’ capacity to vaccinate against monkeypox, easing the current supply crunch as cases continue to rise. But some experts worry officials have scant data to justify the move, and it could backfire.
“It’s clear we need to accommodate many more people for vaccination than we have the ability to with the amount of vaccine we have,” said Michael Osterholm, a public health researcher at the University of Minnesota. “We’re between a rock and a hard place, and when that happens, we need to explore all options for maximizing vaccine use,” he said.
“But we need more data on what will happen if we use a much lower dose” and how protective the method will be for immunocompromised people, he said. “These are questions that need to be answered, and at the same time we can’t wait months to answer them.”
Why is the government doing this?
In short, to squeeze more doses out of the U.S.’s limited supply of the Jynneos vaccine. The federal government has mobilized about 602,000 doses of Jynneos — the only vaccine currently licensed against monkeypox — which currently must be delivered in two doses, far short of the amount needed to cover the estimated 1.6 million people the Centers for Disease Control and Prevention deems at highest risk. If the existing supply could be increased fivefold, as the FDA suggests, officials would have enough vaccines to cover those at highest risk.
The U.S. has about 100 million doses of an older monkeypox vaccine, ACAM2000, but it comes with serious side effects and cannot be taken by people who are immunocompromised. Since about 41 percent of identified monkeypox cases also have HIV, it’s not a suitable alternative for many.
Can’t we just buy more vaccine?
The U.S. has already bought 6.9 million doses from Bavarian Nordic, the small Danish pharmaceutical company that manufactures Jynneos. But a small fraction of those doses have arrived, and the next batch of 150,000 doses won’t arrive until September, officials estimate. Vaccinating as many eligible people as possible as soon as possible is a key tool to help contain the virus.
The World Health Organization estimates there are about 16 million doses of Jynneos (known as Imvanex in Europe and Imvamune in Canada) worldwide, but most of these are frozen in bulk bags. Transferring the stored vaccines into vials ready for use is a slow process that will take several months. More doses won’t get made until 2023, since Bavarian Nordic closed its manufacturing facility in spring to focus on other vaccine products, and it takes time to ramp up production.
Less than a decade ago, the U.S. national stockpile boasted about 20 million doses, a backstop in case of a bioterror attack. But that stockpile dwindled to less than 3,000 doses earlier this year, as officials declined to replenish expired doses and instead invested in a freeze-dried version of the vaccine.
What is an intradermal injection, and why does it require less vaccine?
Intradermal injections are not new and have been used in the past to stretch limited vaccine supply for other conditions, including influenza. This method of delivering vaccine — using a thinner needle to inject less vaccine product into the skin, as opposed to injecting more into the underlying fat or muscle, is used for several other vaccines, including those against yellow fever and rabies. It’s also used for tuberculosis testing.
Intradermal vaccines require less vaccine because skin is especially sensitive, immunologically speaking. Since skin interfaces with the outside world, it’s jam-packed with cells called antigen-presenting cells that kickstart the immune response. When a virus gets into the skin, these cells glob on and figure out the most salient feature of the virus then flag that feature to other immune cells so they can recognize the invader. Because of the density of these cells in the skin, a little vaccine goes a long way.
How do we know it’s effective?
There’s only one published study that has directly compared intradermal and subcutaneous injections of the Jynneos vaccine, and it was relatively small. Similar immune responses, as measured by antibody levels, were seen in about 150 people who received the standard two-dose subcutaneous regimen and about 150 individuals who got about one-fifth the dosage delivered intradermally, suggesting the methods might be interchangeable. However, long-term immune responses were slightly lower in those who got the intradermal shot. It’s unclear how well these lab-measured immune responses predict real-world protection against monkeypox.
The Infectious Diseases Society of America “agrees with the strategy under consideration by the FDA,” according to a statement sent to the Washington Post by the society’s president, Daniel McQuillen.
Some experts are more wary. “My biggest concern is the fact that there’s a lot we don’t know about the standard dose regarding its completeness and durability of protection,” said Jay Varma, a physician and public health researcher who specializes in infectious diseases at Weill Cornell Medicine. “I’m hesitant to recommend that we use intradermal vaccination as our primary approach until there’s more data to show that it produces a comparable immune response as the standard dose.”
What are the downsides?
The biggest possible drawback is that the reduced dosage regime might prove less effective in the real world than in the 2015 study. If that happens, the U.S. may expend much of its limited supply to a vaccination protocol that doesn’t offer much protection to people at risk. It might also take time to figure out the right intradermal dosage or whether the technique is more suitable for certain people — such as those with healthy immune systems.
“We don’t really understand what an intradermal dose for this vaccine will do for immunocompromised individuals,” said Osterholm. “We need those data to understand how much protection it provides,” he added, especially since such a high proportion of monkeypox cases so far in the U.S. are in people who also have HIV.
Even if intradermal injections prove just as effective as the standard method, implementing them could prove complicated. Intradermal injections are somewhat trickier to administer than a jab into the muscle or under the skin, the standard route for most vaccines in the U.S., and not everyone who gives monkeypox shots now may know how to give them by this less-common method.
“You’re going to have to train your vaccinators to do this,” said Varma. “It’s not technically very complex, but it will take some time.” Errors in administration might result in a sub-optimal dose, conferring sub-optimal protection. In addition to a widespread education campaign, other logistical actors will have to be sorted out too, such as ensuring locations have the proper syringes for intradermal injections.
Failure could have broader consequences too. “If it turns out this route isn’t effective, it could reduce confidence in the monkeypox vaccine and vaccines generally, Varma said. “Vaccines that don’t do what you say they’re going to do have spillover effects that can harm other vaccine programs.”
Will we be tracking how well intradermal vaccinations are working?
The National Institutes of Health is reportedly organizing a clinical trial to investigate intradermal injections and test how much protection one dose of Jynneos confers.
“Studies looking at this need to be immediate,” said Osterholm, “not months off.”
In general, reports of vaccinated people getting the virus would filter up through local and state health departments and will be analyzed by the CDC. As cases accumulate, scientists will be able to sort out how well the new method works, and the CDC is developing a portfolio of projects to investigate, said Rochelle Walensky, the director of the CDC in a press briefing on Tuesday.
Who should get the shot?
Right now in the U.S., the monkeypox virus is primarily circulating among men who have sex with men. The CDC recommends vaccination for people who know they’ve been exposed to monkeypox, as well as those at higher risk — including people who know that a sexual partner in the past two weeks has been diagnosed with monkeypox and people with multiple sexual partners in that time in areas with known monkeypox cases.
Some areas have somewhat different guidance. New York City’s Department of Health expanded vaccine eligibility to any gay, bisexual or other man who has sex with men and/or transgender, gender nonconforming or gender nonbinary people, for instance.
Thanks to Alicia Benjamin for copy editing this article.