WASHINGTON — It sounded like a simple solution to the monkeypox vaccine shortage: By simply changing the way doses are administered, the federal government could vaccinate five times as many people with the supply it has.
But the approach — injecting one-fifth of the current dose into the skin instead of the full dose into the underlying fat — isn’t really that simple, experts say. And some federal officials are concerned about changing the method without more research, even though Dr. Robert M. Califf, head of the Food and Drug Administration, called Thursday’s proposal promising.
Some outside experts also urge caution. “From a basic science perspective, it should work,” said Dr. Jay K. Varma, director of the Cornell Center for Pandemic Prevention and Response. “But of course there are many things in life, in science, that we think should work, but when we actually do them, they don’t.”
Stretching the doses of the Jynneos vaccine could help the federal government solve a predicament partly of its own making. Despite investing more than $1 billion to develop a two-dose vaccine to be used against both monkeypox and smallpox, the government has only 1.1 million shots on hand, in part because it has been slow to order bulk stocks of vaccine for processing into vials.
That supply is enough to cover 550,000 people, but about three times as many doses are needed to cover the 1.6 to 1.7 million Americans who, according to the Centers for Disease Control and Prevention, are at high risk of contracting monkeypox. Currently, the virus is spread primarily through skin-to-skin contact during sex among gay and bisexual men, according to the CDC.
Some federal officials hope that by injecting a smaller dose of the vaccine between the layers of the skin, called an intradermal injection, the Biden administration can stop the outbreak before it spreads more widely.
But some experts argue that this approach is not well-studied. They also warn that some vaccinators will need training to properly administer shots, which could slow vaccination efforts. Otherwise, the government may waste the doses instead of saving them.
An intradermal injection involves carefully inserting a needle into the skin layer, a thin space with immune cells. Experts say that if the vaccinator digs too deep and injects the dose into the fat, the patient may not receive enough vaccine. But if the needle is not inserted far enough, some of the vaccine can leak back.
“If you’re injecting a lower dose and you’re not injecting it properly into the skin — you could be injecting in the wrong place — you may not be injecting a protective vaccine,” said retired vaccinologist Dr. Phil Krause. senior FDA vaccine regulator last year and worked on agency licensing for Jynneos. “When you’re asking for it to be done across the country in millions of doses, it’s a lot easier to make mistakes in the administration of the vaccine.”
On the other hand, the method has a track record. It was used in polio vaccination campaigns when doses were limited, and for skin tests for rabies and tuberculosis.
What you need to know about monkeypox virus
What is monkey pox? Monkeypox is a virus similar to smallpox, but the symptoms are less severe. It was discovered in 1958 after an outbreak of the disease in monkeys that were kept for research. The virus was primarily found 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 emergency.
“This is not an entirely new concept,” said Dr. Anthony S. Fauci, President Biden’s chief medical adviser. “We thought of this as a vaccine shortage strategy many years ago.”
Vaccinators used special bifurcated needles in smallpox vaccination campaigns, which allowed them to give intradermal injections more uniformly and cheaply.
Dr. John Beigel, deputy director of clinical research at the National Institutes of Health, said a government-sponsored Jynneos study published in 2015 compared the intradermal approach with a standard injection method and found it produced comparable levels of neutralizing antibodies, a measure of immune strength. answer. Intradermally, the method caused more redness, swelling and itching, but the standard injection was more painful.
Dr. Beigel said switching to the intradermal method is a better option for preserving the vaccine than giving just one shot, as some jurisdictions currently do, because studies have shown that a single shot does not elicit as strong an immune response.
“A single dose is unlikely to be effective,” he said, adding that the intradermal method “is an acceptable method.”
Although the 2015 trial involved hundreds of participants, some experts point out that it was a single study that was limited in what it measured. The NIH researchers planned to test the intradermal strategy for Jynneos in a trial that was to begin in a few weeks. But results were not expected until late fall or early winter, and the plan was still up in the air.
Dr. H. Clifford Lane, clinical director of the Dr. Fauci National Institute of Allergy and Infectious Diseases at the NIH, said that while researchers can get information by observing people who get the shot, a traditional clinical trial would provide a clearer picture.
“I can understand what to do as long as it’s very clear why it’s being done,” he said of the intradermal strategy. “The question is: How can we increase current supply without significantly compromising efficiency?”
Another question is how well the vaccine will actually work: It was licensed in 2019 for use against both monkeypox and smallpox after studies showed it provoked a stronger immune response than the previous vaccine. Federal officials said the drug itself was approved because it differed favorably from an even earlier vaccine.
Monkeypox is rarely fatal, and no deaths have been reported in the United States. Symptoms usually disappear within two to four weeks. But as the outbreak has grown from eight reported cases in late May to 7,510 now, the administration is scrambling to improve vaccination rates and the availability of tests and treatments.
For now, the outbreak is almost entirely confined to men who have sex with men, with those who have multiple partners considered particularly at risk. But so far five cases involving children have been reported. The Illinois Department of Public Health announced Friday that an adult who works at the day care center has tested positive for monkeypox and that children and other staff there are being tested.
Thursday’s declaration of a public health emergency allowed the federal government to expedite the monkeypox investigation and approve grants, but did not invoke the FDA’s emergency powers. The injection regimen change would require a second type of emergency declaration, giving the Food and Drug Administration more leeway to issue emergency use permits.
Federal regulatory agencies can issue emergency approvals for products if they believe the potential benefits outweigh the potential risks. At the start of the coronavirus pandemic, the Trump administration issued a similar emergency declaration, allowing the FDA to make Covid-19 vaccines available to Americans many months before regulators gave full approval.
Dr. Calif, the FDA commissioner, said Thursday that regulators will continue to make sure the vaccine is delivered in a safe and effective way. He said regulators would likely decide in the next few days whether to pursue an intradermal strategy, but that it “looks good right now” — a comment that some outside experts said seemed to preempt discussions of career regulators.
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Emily Cochran and Tracy Tully contributed reporting.
