Officials Wrestle With Whether to Allow New Monkeypox Vaccination Strategy – The New York Times

WASHINGTON — It sounded like a simple solution to the shortage of monkeypox vaccine: Merely by changing the way doses are injected, the federal government could vaccinate five times as many people with the supply it has in hand.

But the approach — injecting one-fifth of the current dose into the skin instead of a full dose into underlying fat — is not actually all that simple, experts say. And some federal officials are concerned about changing the method without more research, even though Dr. Robert M. Califf, the head of the Food and Drug Administration, described the proposal on Thursday as promising.

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

Stretching out doses of the vaccine, Jynneos, could help the federal government resolve a predicament partly of its own making. Even though it invested more than $1 billion developing the two-dose vaccine to use against both monkeypox and smallpox, the government only has 1.1 million shots on hand, partly because it was slow to order bulk vaccine stocks to be processed 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 million to 1.7 million Americans who, according to the Centers for Disease Control and Prevention, are at high risk of monkeypox. For now, the virus has been spreading primarily through skin-to-skin contact during sex among gay and bisexual men, the C.D.C. has said.

Some federal officials are hoping that by injecting a smaller dose of the vaccine between skin layers, called an intradermal shot, the Biden administration could tamp down the outbreak before it spreads more widely.

But some experts argue that this approach has not been sufficiently studied. They also warn that some vaccinators will need training to properly deliver the shots, which could slow vaccination efforts. Otherwise, the government could end up wasting doses, not saving them.

Intradermal injection involves carefully guiding a needle into skin layers, a thin space with immune cells. If a vaccinator goes too deep and inserts the dose into fat, the patient might not receive enough vaccine, experts say. But if the needle is not inserted far enough, some of the vaccine could leak back out.

“If you’re giving a lower dose and you don’t inject it properly into the skin — you might inject it into the wrong place — you may not be giving a protective vaccine,” said Dr. Phil Krause, who retired as a senior F.D.A. vaccine regulator last year and worked on the agency’s licensing of Jynneos. “If you ask this to be done nationwide in millions of doses, it’s a lot easier for there to be mistakes made in the administration of the vaccine.”

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

“It’s not a brand-new concept,” said Dr. Anthony S. Fauci, President Biden’s chief medical adviser. “We were thinking about this as a strategy in the event of a paucity of vaccines years ago.”

Vaccinators have used special bifurcated needles in smallpox inoculation campaigns that have allowed them to perform intradermal injections more uniformly and cheaply.

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 with the standard injection method and found that it triggered a comparable 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 vaccine than administering just a single shot, as some jurisdictions are now doing, because research has shown that one shot does not prompt nearly as strong of an immune response.

“One dose is not likely to 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 measured. Researchers at the N.I.H. had been planning to test the intradermal strategy for Jynneos in a trial that was set to begin in a few weeks. But results were not expected until the 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 N.I.H., said that while researchers could glean insight by following people who get vaccinated, a traditional clinical trial would provide a clearer picture.

“I can understand doing it 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 the current supplies without significantly compromising efficacy?”

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 an earlier vaccine. That drug itself was approved because it compared favorably to an even earlier vaccine, federal officials said.

Monkeypox is rarely fatal and no deaths have been reported in the United States. Symptoms typically resolve within two to four weeks. But with the outbreak spiraling from eight reported cases in late May to 7,510 now, the administration is scrambling to try to improve the vaccination rate and the availability of tests and treatments.

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

Thursday’s declaration of a public health emergency allowed the federal government to speed up investigations of monkeypox and approve grants, but did not invoke the F.D.A.’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 use authorizations.

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

Dr. Califf, the F.D.A. commissioner, said on Thursday that regulators would continue to ensure the vaccine was delivered in a safe and effective manner. He said regulators would probably decide in the next few days whether to go with the intradermal strategy, but that it was “looking good right now” — a comment that some outside experts said seemed to get ahead of deliberations by career regulators.

Emily Cochrane and Tracey Tully contributed reporting.