Still, concrete data on the vaccine’s efficacy are unclear, and some experts say not enough is known about how the low-dose intradermal strategy might affect the protection it provides in the real world.
Even at the initial dose, “there is no traditional evaluation of this vaccine,” Dr. Robert Califf, commissioner of the U.S. Food and Drug Administration, said Tuesday. It was approved for emergency use based on studies of immune responses, not clinical results, because there have been no outbreaks of smallpox or monkeypox large enough to test it.
The intradermal route “may increase the number of doses available in an emergency situation,” the study results said. Last week, the United States declared monkeypox a national public health emergency.
U.S. officials said Tuesday that there are plans to collect real-world data on the vaccine and that the National Institutes of Health will begin a clinical trial.
The new federal strategy still calls for two doses of the vaccine given 28 days apart, and says people who get their first dose subcutaneously can get their second dose intradermally or subcutaneously.
But some people have concerns about switching to a low-dose intradermal strategy.
“While we appreciate that the federal government is finally ready to look at solutions to help correct vaccine shortages, no effort to protect people’s health should come without proper due diligence and research,” David Harvey, executive director of the National Coalition of STD Directors, said in a statement Tuesday.
“We have serious concerns about the limited amount of research that has been done on this dose and method of administration, and we fear that this 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 forward without data on efficacy, safety, or alternative dosing strategies.”
Chicago’s Department of Public Health said Wednesday it will comply with a federal plan to expand the supply of monkeypox vaccine by changing to smaller doses administered in a different way — but it won’t happen overnight.
“I think it’s going to be a few weeks before we start implementing more broadly,” said Dr. Alison Arwadi, Chicago’s commissioner of public health.
Other city health departments, such as Columbus Public Health in Ohio, are still reviewing the new federal strategy and what it means for their local response.
“Because this guidance is new, we are currently reviewing it to determine the impact on our vaccine, staffing and supply efforts,” Kelly Newman, a spokeswoman for Columbus Public Health, wrote in an email to CNN on Wednesday.
Need for “formal clinical efficacy data”
The effectiveness of Jynneos in preventing monkeypox was initially tested in animals that had been exposed to the virus and can be inferred from antibody responses seen in humans who participated in smallpox clinical trials.
But the Jynneos vaccine was originally developed to help protect the nation against smallpox as a bioterrorism response effort — so there’s not much data yet on how well it protects against monkeypox infection, even with a subcutaneous dose.
“There is no official data on the clinical efficacy of the monkeypox vaccine – but this is not a criticism of the vaccine. In fact, I think it’s a testament to the vaccine development effort that we actually already have a monkeypox vaccine, largely before this large outbreak occurred,” said Dr. Dan Baruch, director of the Center for Virology and Vaccine Research at the Medical Beth Israel Deaconess Center in Boston.
The FDA approved the Jynneos vaccine in 2019 to prevent smallpox and monkeypox, but the approval was mostly to offer a smallpox vaccine option that doesn’t contain live virus. Previously, Sanofi Pasteur Biologics’ ACAM2000 was the only FDA-approved smallpox vaccine. Jynneos is the vaccine of choice in the current outbreak because ACAM2000 has the potential for more side effects and is not recommended for people with severely weakened immune systems.
“Jynneos was a second-generation smallpox vaccine whose use case was to be a back-up vaccine for individuals unable to receive ACAM2000 in the event of a smallpox bioweapon attack,” said Dr. Amesh Adalya, senior scientist at the Johns Hopkins Center for Health Security at the Johns Hopkins Bloomberg School of Public Health.
“We had no intention of using ACAM2000 or Jynneos for monkeypox,” he said. “Even though they were effective against it, it wasn’t considered something they were developing it for.”
When Jynneos was approved, FDA officials said its effectiveness for preventing smallpox was determined by a clinical trial of about 400 healthy adults. Half of them got ACAM2000 and half got Jynneos.
The US Centers for Disease Control and Prevention estimates that the Jynneos and ACAM2000 smallpox vaccines are at least 85% effective in preventing monkeypox.
“Although we have no clinical efficacy data, it is likely that Jynneos will be very effective, because of what we know about the smallpox vaccine and because of the efficacy of Jynneos against monkeypox in animals,” Baruch said.
He added that “in general, vaccines are usually more effective in preventing the severe consequences of the disease than in preventing infection with the pathogen.”
“We can be confident that this is likely to be a highly effective vaccine, but the specifics of it in terms of exact numerical efficacy — and whether it’s going to be prevention of infection or prevention of severe disease — those details are really not known at this point,” he said. Baruch. “I think people at high risk should be vaccinated, but right now I don’t think it’s possible to give very precise guidance on exactly what that protection will look like.”
Ability to “significantly improve” availability
Uncertainty surrounding the effectiveness of the Jynneos vaccine will be increased by the shift to a lower dose of the vaccine in the real world, outside of a clinical trial, Dr. Philip Krause, former deputy director of the FDA’s Office of Vaccine Research and Review, and the physician of infectious diseases Dr. Luciana Borio wrote in Stat News on Tuesday.
“If the vaccine can be administered at lower doses without risk to efficacy, lower-dose intradermal injections make sense,” Krause and Borio wrote. “But this strategy can also backfire. If there is a risk to effectiveness, it may be better to focus available full doses of vaccine on individuals at highest risk—men who have sex with multiple male partners—to provide the best chance of getting the epidemic under control. .”
During the outbreak, the vaccine was administered to health care workers treating people with monkeypox, close contacts of patients, and people who managed to find doses at local clinics. The CDC has estimated that at least 1.5 million people in the US are eligible for the monkeypox vaccination.
“We have a tail around the corner,” Dr. Stacey Lane, a clinician at Central Outreach Wellness Center in Pittsburgh, said Tuesday of her clinic’s search for a monkeypox vaccine.
The US Department of Health and Human Services has delivered more than 670,000 doses of the Jynneos vaccine from the Strategic National Stockpile to support local monkeypox response efforts on the ground.
“In addition, SNS is preparing to distribute approximately 400,000 additional vials to states and jurisdictions as part of the next phase of the national vaccine strategy,” according to the White House. “Jurisdictions that administer 90% of their current vaccine supply may request additional doses sooner.”
And because of the authorization for intradermal injections, “the 400,000 vials of vaccine in the SNS inventory that have been allocated but not yet distributed have the potential to provide up to 2 million doses via intradermal administration. In addition, vaccines that have been received by jurisdictions , but not yet applied, are suitable for intradermal use.”
Lane said switching to an intradermal strategy could “significantly improve” vaccine availability. Her clinic has ordered the shorter syringes needed for intradermal administration of the vaccine, the same ones used for tuberculosis tests, she said.
“I ordered them this afternoon,” she said Tuesday, before the FDA issued its approval.
Lane said many of her patients worry about getting monkeypox, and she points them to the ACAM2000 vaccine data as a starting point for how well the Jynneos vaccine can protect against monkeypox.
“What we’re educating people about is that we know from historical data that the ACAM2000 vaccine that was historically administered in Africa was about 85 percent protective against monkeypox. “We know that these orthopox families of viruses tend to respond to the same treatment, and that the vaccine is somewhat effective,” Lane said.
She added that she does not expect concerns about the new vaccination strategy.
“We really don’t see any hesitation about the vaccine, at least at this stage,” she said.
Dr. Paulette Gray Riveria agreed that the intradermal strategy could be an effective way to increase supply.
“Given that a smaller volume of vaccine is required for an intradermal compared to a subcutaneous dose, Jynneos intradermal injections could be a reasonable option to maximize delivery without compromising vaccine protection,” Gray Riveria, M.D. family medicine with virtual health platform PlushCare and regional medical director for the state of Louisiana, wrote in an email to CNN.
“Scientists are actively investigating to determine whether immune cells under the skin can activate an antibody response with equal or greater efficiency compared to the subcutaneous route.”
CNN’s Jen Christensen contributed to this report.
Add Comment