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Monkeypox Vaccines Will Now Be Administered Intradermally. Here’s What That Means

intradermal injection

Verywell / Mira Norian

Key Takeaways

  • To stretch the limited supply of the monkeypox vaccine Jynneos, the FDA granted an emergency use authorization to administer the vaccine intradermally. 
  • The dose-sparing strategy will allow providers to immunize five people with a vial designed for a single shot. 
  • The smaller dose is given underneath the skin, rather than into the deeper layer of fatty tissue as is typical for this vaccine.
  • Other vaccines and tests are given intradermally, and it’s considered a safe and effective technique.

Monkeypox cases are surging and the U.S. doesn’t have enough vaccine to protect everyone who is at high risk for getting sick with the disease.

To stretch its current supply of the monkeypox vaccine, called Jynneos, the Food and Drug Administration (FDA) announced on August 10 that providers can now use a single-dose vial to administer five vaccines.

The smaller dose is to be given under the topmost layer of the skin, rather than in the fatty tissue below. This technique is called intradermal vaccination.

There are at least 1.6 million people in the U.S. who are estimated to be at an elevated risk for monkeypox. Protecting this whole group requires at least 3.2 million doses of the two-dose vaccine. Only about half that amount is expected to become available before the end of the year.

The dose-sparing approach would allow the government to make thousands of doses usable for millions of people. But the data supporting the move comes largely from a single study, and some experts are raising concerns about whether the new strategy will adequately protect vaccines.

What to Expect From an Intradermal Vaccine

Most routine vaccines in the U.S. are given intramuscularly, or into the muscle layer below the skin and fat. For these types of injections, the needle meets your arm at a 90-degree angle. COVID-19 and flu vaccines, for example, are intramuscular injections.

Jynneos was initially approved in 2019 to be administered a different way: subcutaneously. The subcutaneous layer of your skin, also called the hypodermis, is made up of fat and other tissues. It is the deepest of the three layers of the skin and is an ideal site for injection medications, such as insulin, epinephrine, and morphine. Because this is not as deep as your muscle, the needle will be placed at a 45-degree angle for the injection.

subcutaneous injection

Verywell / Mira Norian

The new emergency use authorization for monkeypox reserves subcutaneous injection only for minors. Anyone age 18 and older who is eligible for the vaccine will receive 0.1 milliliters of Jynneos—a fifth of the original dose—intradermally.

Jynneos is a two-dose vaccine. The CDC says people who receive one dose of the standard subcutaneous shot, such as people under the age of 18, may get their second shot intradermally.

Intradermal injections deliver vaccine or medication to the dermis—the topmost layer of the skin. This technique is relatively rare because it’s challenging to do it correctly. But there’s a chance you’ve had an intradermal injection before. It’s commonly used to test for tuberculosis and allergies.

intradermal injection

Verywell / Mira Norian

Intradermal shots are much shallower than subcutaneous or intramuscular injections. The health provider will hold your hold skin taut and insert the needle into the dermis at an angle ranging from 5 to 15 degrees. You’ll feel a quick pinch.

In a video explainer, the CDC says to inject the vaccine until there is a “noticeable, pale elevation of the skin.” The resulting small, vaccine-filled welt should disappear within days.

Why Intradermal Vaccination Works With Less Vaccine

Vaccines work by introducing the body to a foreign substance, called antigen. This antigen triggers the immune system to create antibodies and other special cells that can recognize and attack that antigen if they encounter it again, like in the case of a viral infection.

When someone gets vaccinated, certain cells near the site of vaccination carry the antigen to immune cells deeper in the body. This jumpstarts the body’s defense-building process.

Dendritic cells, which are abundant in the skin, are especially quick at shuttling antigens to immune cells. Thanks to the efficiency of these cells, intradermal vaccination can elicit an immune response more quickly than other techniques while using less vaccine, said Paul Offit, MD, director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.

But Does It Work Well Enough?

The FDA decision to switch to a dose-sparing strategy is based largely on a 2015 study of about 523 participants, in which 191 participants received Jynneos intradermally.

That study measured the level of neutralizing antibodies induced by different vaccination approaches. Antibody levels are a key metric for understanding how well a vaccine works. But these types of studies aren’t always predictive of how well the vaccine will perform in real-world settings.

It will be important, Offit said, that researchers follow up with people who got the vaccine intradermally to see how protective the dose-sparing strategy actually is.

There’s also a higher likelihood of error when administering the vaccine intradermally. If the needle is angled too sharply, the low-dose vaccine will be sent too deep, causing it to be less effective.

“The FDA is presenting studies done under controlled conditions,” Offit said. “Once you put it out there into the real world, there are going to be people who are going to be better and others who are not so good at giving intradermal inoculations.”

Bavarian Nordic, the company that manufactures Jynneos, has expressed some hesitancy about the data supporting the intradermal approach.

Bavarian Nordic president Paul Chaplin wrote a letter to the FDA commissioner and the Secretary of Health and Human Services following the decision to split doses. The company, he wrote, is “fully supportive of dose-sparing approaches, such as delaying the second vaccination,” but it has “some reservations” about the intradermal approach.

Still, Chaplin said the company will work with U.S. officials to carry out the authorization, and continue to conduct studies on safety and efficacy of different vaccination approaches.

How Side Effects Compare

According to the FDA, Jynneos side effects were similar in both people who received subcutaneous vaccination and those who were vaccinated intradermally, and none of the reported side effects were severe.

In the 2015 study, fatigue was the most common side effect regardless of how Jynneos was administered. Each group reported similar levels of muscle aches, chills, headaches, and other side effects.

Participants who received the Jynneos shot intradermally tended to have more itching and redness that lasted over two weeks.

“We don’t fully know what this means for long-term protection, and we don’t fully know what it means for safety,” Ellen Carlin, DVM, assistant research professor at the Center for Global Health Science and Security at Georgetown University, said in a statement provided to Verywell. “We do know that there was a higher incidence of injection-site reactions in this [intradermal] cohort of people.”

Is a Small Dose Better Than One Dose?

In mid-July, some states began delaying the second dose of Jynneos to get at least one shot in as many arms as possible with their limited supply.

The FDA said this approach was “not considered acceptable.” But research indicates a single dose can create a strong and long-lasting immune response.

Scientists don’t actually know much about how well any of the vaccination strategies work in the real world. That’s because Jynneos was licensed based on data from both animal experiments and immune response studies in humans. But due to logistical and ethical concerns about running monkeypox clinical trials, there have been no large-scale studies on the likelihood of vaccinated people getting sick compared to a placebo group.

As long as a vaccine regimen causes the immune system to build a strong defense against the monkeypox virus, scientists expect it will protect against severe disease.

Science reports that the National Institute of Allergy and Infectious Diseases will start a randomized control study in September to test how well two one-fifth doses compare to two full doses. But this study will also only test the immune response, rather than how well the vaccines actually protect against disease.

Offit said that once people are vaccinated, they may believe they are protected against monkeypox and be less cautious during behaviors known to spread the virus, including sex. If it turns out the smaller dose isn’t as effective as the subcutaneous shot, the disease could continue to spread at high rates.

What This Means For You

If you are eligible for a monkeypox vaccine, know that it may feel different from other injections you’ve received before. That’s because the vaccine will only enter the top layer of your skin, rather than your muscle or deeper layers of skin targeted by other vaccines and injected medications. Researchers aren’t sure exactly how effective this intradermal approach will be.

3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Centers for Disease Control and Prevention. Healthcare Providers/Professionals: Administer the Vaccine(s)

  2. Frey SE, Wald A, Edupuganti S, et al. Comparison of lyophilized versus liquid Updated vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects. Vaccine. 2015;33(39):5225-5234. doi:10.1016/j.vaccine.2015.06.075

  3. Earl PL, Americo JL, Wyatt LS, et al. Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virusProc Natl Acad Sci U S A. 2008;105(31):10889-10894. doi:10.1073/pnas.0804985105

Additional Reading

By Claire Bugos
Claire Bugos is a health and science reporter and writer and a 2020 National Association of Science Writers travel fellow.