The US Food and Health Administration (FDA) on Tuesday green-lighted splitting the monkeypox vaccine dose and injecting it into the outer layers of the skin. Experts say it is a simple and effective way to increase the number of available doses; however, the new strategy might pose challenges in administering the vaccine.
The FDA issued an emergency use authorization (EUA) for the JYNNEOS vaccine to allow healthcare providers to use the vaccine by intradermal injection in individuals 18 years and older who are at high risk for monkeypox infection. The officials say this will increase the total number of doses available for use by up to five-fold.
“The FDA quickly explored other scientifically appropriate options to facilitate access to the vaccine for all impacted individuals. By increasing the number of available doses, more individuals who want to be vaccinated against monkeypox will now have the opportunity to do so,” said FDA Commissioner Robert M. Califf, MD.
The EUA also allows the use of the vaccine by subcutaneous injection in individuals younger than 18 years who are at high risk of monkeypox infection.
What is an intradermal route?
The dose-sparing approach will allow splitting the existing dose into five and injecting it intradermally — to the dermis or epidermis, the outer layers of human skin. Currently, the monkeypox vaccine is delivered into the subcutaneous tissue, or the fat layer under the skin.
The intradermal route is widely used to deliver the Bacille Calmette-Guérin vaccine against tuberculosis and rabies vaccines, while most other vaccines are delivered by the intramuscular or subcutaneous routes.
Epidermal and dermal layers of the skin contain the antigen-presenting cells (APCs) that are thought to play a significant role in mediating an efficient and protective immune response to specific vaccines, Melbourne Vaccine Education Centre explains.
APCs present specific antigens to particular cells in the immune system that are responsible for eliciting an immune-mediated response that in turn creates memory cells and antibodies.
What do experts say?
Dr. Richard Kennedy, co-director of Mayo Clinic's Vaccine Research Group, says that the authorities' decision is based on a study from 2015 comparing the subcutaneous route of vaccination using the full dose and the intradermal route using one-fifth of a dose.
The study showed no significant difference in immune response and systemic reactions, such as headache, fever, muscle aches, and pains. However, local reactions like pain and itching were a little more frequent and intense in people who received the jab intradermally.
A 2020 study found that a fractional intradermal dose is effective in vaccinating against influenza, rabies, and hepatitis B. Another study in 2004 showed that injecting one-fifth of influenza vaccine dose intradermally elicited a similar or better immune response.
Dr. Ashley Lipps, an infectious medicine physician at the Ohio State University Wexner Medical Center, says that people who administer subdermal vaccines would need to be specifically trained, as there is less room for error when administering this route.
“For instance, the vaccine may not be as effective if administered too deep, as opposed to in between the layers of the skin where it is intended to be administered,” she said in an e-mail.
However, Dr. Kennedy says most healthcare providers and nurses should be familiar with the method, as tuberculosis tests in the US are taken intradermally. "It is not a difficult technique to learn," he said.
What are the challenges?
Dr. Kennedy at the Mayo Clinic's Vaccine Research Group says that dose-sparing is a relatively "simple and straightforward approach" to increase the number of available monkeypox vaccine doses. However, adding new steps to the system can introduce some challenges.
"They would need to have an adequate supply of sterile saline; they would also need to be able to dilute the vaccines onsite and use them immediately. Then, of course, they would need five times more needles and syringes," he says.
Dr. Kennedy notes that JYNNEOS and ACAM2000 vaccines have never been tested in the real world against monkeypox.
“All the available data suggest these vaccines will be highly effective, but it remains to see if the real world data supports those assumptions.”
The US has secured 1.1 million doses of JYNNEOS vaccine manufactured by Bavarian Nordic. It is licensed as a two-dose product, each of which should be administered 28 days apart.
The Centers for Disease Control and Prevention (CDC) estimates about 1.7 million people in the US are at high risk of catching monkeypox.
As of Wednesday, there are 9,429 confirmed cases of monkeypox in the US.