Key points to remember
- To stretch the limited supply of the Jynneos monkeypox vaccine, the FDA granted an emergency use authorization to administer the vaccine intradermally.
- The dose-saving strategy will allow providers to vaccinate five people with a vial designed for a single injection.
- The smaller dose is given under the skin, rather than in the deeper layer of fatty tissue, as is usually the case with this vaccine.
- Other vaccines and tests are administered intradermally and this technique is considered safe and effective.
Cases of monkeypox are on the rise, and the United States does not have enough vaccines to protect everyone at high risk from contracting the disease.
To expand its current supply of monkeypox vaccine, called Jynneos, the 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 should be administered under the top layer of the skin, rather than into the fatty tissue below. This technique is called intradermal vaccination.
There are at least 1.6 million people in the United States who are considered high risk for monkeypox. Protection of this entire group requires at least 3.2 million doses of the two-dose vaccine. Only about half of this amount should be 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 decision largely comes from a single study, and some experts are concerned about whether the new strategy will adequately protect vaccines.
What to expect from an intradermal vaccine
Most routine vaccines in the United States are given intramuscularly or into the muscle layer under the skin and fat. For these types of injections, the needle meets your arm at a 90 degree angle. The COVID-19 and flu vaccines, for example, are intramuscular injections.
Jynneos was originally approved in 2019 to be administered in 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 skin and is an ideal site for injections of drugs, such as insulin, epinephrine and morphine. Because it’s not as deep as your muscle, the needle will be placed at a 45 degree angle for the injection.
New emergency use authorization for monkeypox reserves subcutaneous injection only for minors. Anyone aged 18 and over who is eligible for the vaccine will receive 0.1 milliliters of Jynneos, one-fifth of the initial dose, intradermally.
Jynneos is a two-dose vaccine. The CDC says people who receive one dose of the standard subcutaneous injection, such as people under 18, can receive their second injection intradermally.
Intradermal injections deliver a vaccine or drug into the dermis, the top layer of the skin. This technique is relatively rare because it is difficult to do it correctly. But it is possible that you have already received an intradermal injection. It is commonly used to test for tuberculosis and allergies.
Intradermal injections are much shallower than subcutaneous or intramuscular injections. The healthcare provider will hold your skin taut and insert the needle into the dermis at an angle ranging from 5 to 15 degrees. You will feel a quick pinch.
In a explanatory video, the CDC says to inject the vaccine until there is a “visible, pale elevation of the skin.” The resulting small vaccine mark should disappear within a few days.
Why intradermal vaccination works with less vaccine
Vaccines work by introducing a foreign substance, called an antigen, into the body. This antigen triggers the immune system to create antibodies and other special cells that can recognize and attack this antigen if they encounter it again, such as in the case of a viral infection.
When a person is vaccinated, certain cells near the vaccination site carry the antigen to immune cells deeper in the body. This restarts the process of building the body’s defense.
Dendritic cells, which are abundant in the skin, are particularly quick to shuttle between antigens and immune cells. Thanks to the efficiency of these cells, intradermal vaccination can trigger an immune response faster than other techniques while using less vaccine, said Paul Offit, MDdirector of the Vaccine Education Center and attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.
But does it work well enough?
The FDA’s decision to switch to a dose-saving strategy was largely based on a 2015 study of approximately 523 participants, in which 191 participants received Jynneos intradermally.
This study measured the level of neutralizing antibodies induced by different vaccination approaches. Antibody levels are a key metric for understanding how a vaccine works. But these types of studies aren’t always predictive of vaccine performance under real-world conditions.
It will be important, Offit said, for researchers to follow people who received the vaccine intradermally to see how protective the dose-sparing strategy actually is.
There is also a greater likelihood of error when administering the vaccine intradermally. If the needle is angled too far, the low dose vaccine will be sent too deep, making it less effective.
“The FDA presents studies performed under controlled conditions,” Offit said. “Once you put it in the real world, there will be people who will get better and people who won’t be so good at administering intradermal inoculations.”
Bavarian Nordic, the company that makes Jynneos, expressed some hesitation 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 the doses. The company, he wrote, is “fully supportive of dose-saving approaches, such as postponing the second vaccination,” but has “some reservations” about the intradermal approach.
Nonetheless, Chaplin said the company would work with US authorities to obtain clearance and would continue to conduct studies on the safety and effectiveness of different vaccination approaches.
Comparison of side effects
According to FDAside effects of Jynneos were similar in people vaccinated subcutaneously and in those vaccinated intradermally, and none of the reported side effects were serious.
In the 2015 study, fatigue was the most common side effect, regardless of how Jynneos was given. Each group reported similar levels of muscle aches, chills, headaches, and other side effects.
Participants who received the Jynneos injected intradermally tended to experience more itching and redness that lasted for more than two weeks.
“We don’t know exactly what that means for long-term protection, and we don’t know exactly what that means for security,” Ellen Carlin, DVMassistant research professor at the Center for Global Health Science and Security at Georgetown University, said in a statement supplied to Verywell. “We know there was a higher incidence of injection site reactions in this [intradermal] cohort of people.
Is a small dose better than a single dose?
In mid-July, some states began delaying the second dose of Jynneos to get at least one injection in as many arms as possible with their limited supply.
The The FDA said this approach was “not considered acceptable”. But research indicates that just one dose can create a strong and long-lasting immune response.
Scientists don’t really know how well vaccination strategies work in the real world. That’s because Jynneos was licensed based on data from both animal testing and human immune response studies. But due to logistical and ethical issues with running monkeypox clinical trials, there have been no large-scale studies of how likely vaccinated people will get 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 to protect against severe disease.
Science reports that the National Institute of Allergy and Infectious Diseases will launch 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 the actual ability of vaccines to protect against disease.
Offit said 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 the smaller dose turns out not to be as effective as the subcutaneous injection, the disease could continue to spread at a high rate.
What this means for you
If you are eligible for a monkeypox vaccine, be aware that it may look different than other shots you have had before. This is because the vaccine will only penetrate the top layer of your skin, rather than your muscles or the deeper layers of skin targeted by other vaccines and injected drugs. Researchers don’t know exactly how effective this intradermal approach will be.