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Subcutaneous versus intradermal mpox (monkeypox) vaccination: what’s the difference and does it impact side effects?

JYNNEOS mpox (monkeypox) vaccine became available to at-risk individuals across Australia on 8 August 2022 and was initially administered by subcutaneous injection (into the fatty tissue under the skin). Updated guidance from the Australian Technical Advisory Group on Immunisation (ATAGI) now allows intradermal administration (between the outer layers of the skin) of JYNNEOS mpox vaccine in individuals who are not severely immunocompromised and are receiving the vaccine before exposure to the mpox virus (pre-exposure prophylaxis). We take a look at the differences in vaccine delivery methods and if there is an impact on side effects.   

What is the difference between subcutaneous and intradermal JYNNEOS mpox vaccination?

Subcutaneous vaccine administration uses a short needle to inject a 0.5 mL dose of the JYNNEOS mpox vaccine into the fatty tissue layer (subcutaneous layer) located between the skin and the muscle. Subcutaneous JYNNEOS mpox vaccines are most commonly given in the upper arm, between the elbow and shoulder. 

Intradermal vaccine administration uses a short needle to inject a 0.1 mL dose of the JYNNEOS mpox vaccine into the space between the two outer layers (epidermis and dermis) of the skin. Intradermal JYNNEOS mpox vaccines are most commonly given in the forearm, between the hand and elbow. Intradermal vaccination will generally create a small, pale bubble on the skin known as a bleb. 

The intradermal injection technique requires specialised training and only providers who have undertaken this training can administer vaccines using this technique. Currently, other vaccines that are administered intradermally include BCG, rabies and hepatitis B vaccines in specific settings. 

Why is Australia now using intradermal administration of the JYNNEOS mpox vaccine?

There is a world-wide shortage of the JYNNEOS mpox vaccine because of the increased demand. Intradermal administration of the JYNNEOS mpox vaccine requires a smaller dose. For every one subcutaneous JYNNEOS mpox vaccine, as many as five intradermal JYNNEOS mpox vaccines can be administered, which allows a much larger proportion of people to be protected with limited supply.

The World Health Organization had declared the mpox outbreak a public health emergency of international concern in July 2022, following which countries around the globe launched vaccination programs, increasing demand for the vaccine.

Is intradermal administration as effective?

Yes, intradermal administration of the JYNNEOS mpox vaccine is as effective as the subcutaneous administration. The dermis has a higher number of cells that stimulate the immune response compared to the fatty subcutaneous tissue, which means a smaller dose of vaccine can be given intradermally to provide similar protection as subcutaneous vaccination. A clinical study in 2015 confirmed that the intradermal administration of JYNNEOS at one fifth of the subcutaneous dose produced a similar immune response compared to the subcutaneous dose.

Does the vaccine delivery method impact side effects?

AusVaxSafety has been actively monitoring the side effect profile of the JYNNEOS mpox vaccine since the rollout started and recently published vaccine safety data analysing subcutaneous and intradermal vaccine delivery.

Individuals who received the JYNNEOS 0.1 mL mpox vaccine intradermally reported slightly higher rates of side effects (57%) than those who received the JYNNEOS 0.5 mL mpox vaccine subcutaneously (50%). This increase is due to a larger proportion of people who received an intradermal injection experiencing a local reaction (pain, redness, swelling and itching at injection site, 55%) than those who received a subcutaneous injection (47%). Increased rates of local reactions are expected with all intradermal vaccinations, which subside over time. 


Medical attendance rates and the impact on routine activities were similar and remained low for both delivery methods.

Click here to view the latest JYNNEOS mpox vaccine safety data