Officials grapple with whether or not to allow new monkeypox vaccination strategy

WASHINGTON — It sounded like a simple solution to the monkeypox vaccine shortage: Just by changing the way doses are injected, the federal government could vaccinate five times as many people with the stock it holds.

But the approach — injecting a fifth of the current dose into the skin rather than a full dose into underlying fat — isn’t really that simple, experts say. And some federal officials are concerned about changing the method without more research, although Dr. Robert M. Califf, the head of the Food and Drug Administration, described the proposal as promising on Thursday.

Some external experts also urge caution. “From a basic science perspective, this should work,” says Dr. Jay K. Varma, the director of the Cornell Center for Pandemic Prevention and Response. “But of course there are a lot of things in life, in science, that we think should work, and then when we actually do them, they don’t.”

Stretching doses of the vaccine, Jynneos, could help the federal government solve a predicament partly caused by itself. Although it has invested more than $1 billion in developing the two-dose vaccine for use against both monkeypox and smallpox, the government has only 1.1 million injections on hand, in part because it has been slow to get bulk vaccine stocks processed into vials.

That supply is enough to cover 550,000 people, but it takes about three times as many doses to cover the 1.6 million to 1.7 million Americans who are at high risk for monkeypox, according to the Centers for Disease Control and Prevention. . For now, the virus spreads primarily through skin-to-skin contact during sex between gay and bisexual men, the CDC said.

Some federal officials hope that by injecting a smaller dose of the vaccine between the layers of skin, called an intradermal injection, the Biden administration can quell the outbreak before it spreads further.

But some experts argue that this approach hasn’t been studied enough. They also warn that some vaccinators need training to properly deliver the shots, which could slow down vaccination efforts. Otherwise, the government could end up wasting doses instead of stockpiling them.

With intradermal injection, a needle is gently guided into the layers of skin, a thin space containing immune cells. If a vaccinator goes too deep and inserts the dose in fat, the patient may not get enough vaccine, experts say. But if the needle is not inserted far enough, some of the vaccine could leak back out.

“If you give a lower dose and don’t inject it into the skin properly — you may be injecting it in the wrong place — you may not be giving a protective vaccine,” said Dr. Phil Krause, who retired as a senior FDA vaccine regulator last year and worked on the agency’s licensing of Jynneos. “If you’re asking to do this in millions of doses nationwide, it’s a lot easier to make mistakes when administering the vaccine.”

On the other hand, the method has a track record. It has been used in polio vaccination campaigns when doses were limited, as well as for rabies and for skin testing for tuberculosis.

“It’s not a brand new concept,” says Dr. Anthony S. Fauci, chief medical adviser to President Biden. “We thought of this years ago as a strategy in the event of a vaccine shortage.”

Vaccinators have used special split needles in smallpox vaccination campaigns that allowed them to perform intradermal injections more uniformly and cheaper.

dr. John Beigel, an associate director of clinical research at the National Institutes of Health, said a government-sponsored study of Jynneos published in 2015 compared the intradermal approach to the standard injection method and found it produced a similar level of neutralizing antibodies, a measure of the strength of the immune response. The intradermal method caused more redness, swelling and itching, but the standard injection was more painful.

dr. Beigel said that switching to the intradermal method was a better option for preserving the vaccine than giving just a single injection, as some jurisdictions are doing now, because research has shown that one injection does not elicit nearly as strong an immune response.

“One dose probably won’t be effective,” he said, adding that the intradermal method is “an acceptable way to go.”

Although the 2015 trial involved hundreds of participants, some experts note that it was a single study that was limited in what it measures. NIH researchers planned to test the intradermal strategy for Jynneos in a trial that would begin in a few weeks. But the results weren’t expected until late fall or early winter, and that plan is up in the air for now.

dr. H. Clifford Lane, the clinical director of Dr. Fauci’s National Institute of Allergy and Infectious Diseases at the NIH said that while researchers could gain insight by following people who get vaccinated, a traditional clinical trial would provide a clearer picture.

“I can understand as long as it’s very clear why it’s being done,” he said of the intradermal strategy. “The question is, how can we stretch current stocks without significantly compromising efficacy?”

Another question is how well the vaccine will actually work. It was approved for use against both monkeypox and smallpox in 2019 after studies showed it elicited a stronger immune response than a previous vaccine. That drug itself was approved because it compares favorably with an even earlier vaccine, federal officials said.

Monkeypox is rarely fatal and no deaths have been reported in the United States. Symptoms usually disappear within two to four weeks. But with the outbreak now rising from eight reported cases at the end of May to 7,510, the administration is trying to improve vaccination coverage and the availability of tests and treatments.

As of now, the outbreak is almost entirely confined to men who have sex with men, with those who have multiple partners believed to be at particular risk. But so far, five cases involving children have been reported. On Friday, the Illinois Department of Public Health announced that an adult who worked at a daycare center had tested positive for monkeypox and that children and other staff there were being screened.

Thursday’s declaration of a public health emergency allowed the federal government to speed up monkeypox research and approve grants, but did not call on the FDA’s emergency powers. Changing the injection mode would require a second kind of emergency declaration, giving the Food and Drug Administration more leeway to issue emergency clearances.

Federal regulators may issue emergency approvals for products when they believe the potential benefits outweigh the potential risks. Early in the coronavirus pandemic, the Trump administration issued the same type of emergency declaration, allowing the FDA to make Covid-19 vaccines available to Americans many months before regulators gave full approvals.

dr. Califf, the FDA commissioner, said on Thursday that regulators would continue to ensure the vaccine was delivered in a safe and effective manner. He said regulators would likely decide in the coming days whether to go with the intradermal strategy, but it “looked good now” — a comment some outside experts said seemed to prejudge career regulators’ deliberations.

Emily Cochrane and Tracey Tully reporting contributed.

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