The Biden administration announced Tuesday that the United States will allow for the use of fractional doses of monkeypox vaccine, a plan that could result in five times as many people being vaccinated than the current approach.
The decision comes days after Health and Human Services Secretary Xavier Becerra declared the monkeypox outbreak a public health emergency.
On Tuesday, Becerra issued a so-called 564 determination, which gives the Food and Drug Administration the power to issue emergency use authorizations for vaccines. In this case, it gives the FDA authority to permit changes to the way the Jynneos monkeypox vaccine, made by the Danish company Bavarian Nordic, is administered.
“Today’s action will allow FDA to exercise additional authorities that may increase availability of vaccines to prevent monkeypox while continuing to ensure the vaccine meets high standards for safety, effectiveness and manufacturing quality,” Becerra said in a statement.
Robert Fenton, the newly appointed White House monkeypox response coordinator, called the move “a game changer.”
“It’s safe, it’s effective, and it will significantly scale the volume of vaccine doses available for use across the country,” Fenton said during a press conference.
The FDA issued an emergency use authorization that permits people delivering the vaccine to use fractional doses — one-fifth of a full dose — via intradermal vaccination to people 18 and older. Fractional dosing has been used in the past in times of vaccine shortages; intradermal administration — depositing the vaccine into rather than under the skin — has been shown to generate strong immune responses with smaller amounts of vaccine than are used in vaccine doses administered under the skin or into a muscle.
Federal officials acknowledged that many health providers may not know how to give an intradermal injection; it is a technique that is not commonly used. Rochelle Walensky, director of the Centers for Disease Control and Prevention, said the CDC will be distributing educational materials to vaccine providers “to help ensure this new strategy can be implemented quickly and as seamlessly as possible.”
The EUA also allows for use of the vaccine in people under 18, which up until now required FDA’s expanded access investigational new drug application to be filed each time a health provider wanted to vaccinate a child or a teen who had been exposed to monkeypox. For people under 18, two full doses, administered subcutaneously, will remain the regimen.
Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, said the EUA will make it easier to use the vaccine in children and teens when the need arises. He explained that intradermal administration can be tricky in very young children, hence the decision to stick with subcutaneous vaccination for children and teens.
Jynneos is licensed as a two-dose vaccine, with the doses given 28 days apart; the vaccine is delivered subcutaneously, or under the skin. With this EUA, the vaccine can now be given as a one-fifth dose, administered intradermally. It will still require two doses given 28 days apart.
A clinical trial published in 2015 showed that the Bavarian Nordic vaccine, when given in this manner, generated a similar immune response to that generated by two full doses given subcutaneously.
The National Institutes of Allergy and Infectious Diseases are in the process of designing another trial to compare a fractional dose regimen and a single, full-dose regimen to the standard two-dose approach, as STAT reported last week. That trial will proceed, but a source said there may be modifications made to the trial design.
Walensky said the CDC has also been working on “a portfolio of vaccine effectiveness projects” to assess how well the vaccine is working. But she said the CDC recommends that people who get vaccinated continue to take steps to protect themselves from infection, especially if they have only had a single dose, “because we don’t yet know how well these vaccines work.”
Some experts have raised concerns about the decision to adopt fractional dosing before conducting more study of the approach. In an opinion piece published Tuesday in STAT, Philip Krause, former deputy director of the FDA’s Office of Vaccines Research and Review, and Luciana Borio, a senior fellow for global health at the Council on Foreign Relations, warned the plan could backfire.
The vaccine, which was approved based on human immunogenicity data and effectiveness studies conducted in non-human primates, did not prevent all infections in the animal, they noted. And health professionals do not have a lot of experience giving vaccines via the intradermal route.
“Vaccines are not typically given intradermally in the U.S., and there is little margin for error,” Borio and Krause wrote. “Mistakes could cause a lower dose of the vaccine to be delivered deeper than intended, with likely lower effectiveness.”
“A hasty decision to try an unproven and risky strategy to stretch the existing vaccine supply may interfere with developing a national plan to quell this outbreak,” they concluded.
The National Coalition of STD Directors — which represents the sexual health clinics that have been at the forefront of the monkeypox response — also questioned the decision.
“To implement a change of course like the administration is proposing requires additional staff, training, supplies like new syringes, and ultimately trust — which has been slowly chipped away each and every time the vaccine strategy changes,” Executive Director David C. Harvey said in a statement.
“We have grave concerns about the limited amount of research that has been done on this dose and administration method, and we fear it will give people a false sense of confidence that they are protected. This approach raises red flag after red flag, and appears to be rushed ahead without data on efficacy, safety, or alternative dosing strategies.”
Some jurisdictions, both internationally and within the United States, have been giving a single dose of the monkeypox vaccine, prioritizing giving more people some protection over giving fewer people the complete regimen. But the FDA and the Centers for Disease Control and Prevention have discouraged that approach. “There are no data available to indicate that one dose of Jynneos will provide long-lasting protection, which will be needed to control the current monkeypox outbreak,” the FDA said in a statement Tuesday.
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