Skip Navigation LinksIntradermal-administration-of-JYNNEOS-smallpox-and-mpox-vaccine-recommended-to-extend-scarce-supplies

State of Cal Logo

State of California—Health and Human Services Agency
California Department of Public Health

November 3, 2022

All Californians

Interim guidance: Intradermal administration of JYNNEOS smallpox and mpox vaccine recommended to extend scarce supplies

Related Materials: Mpox Landing Page Mpox Q&A | Mpox Interim Guidance Intradermal Administration (Spanish) (PDF) | | Mpox Vaccine Q&A for Providers and LHD  

Updates as of November 3, 2022: 

  • Changes to guidelines for intradermal dosing to allow more flexibility.


Smallpox and mpox Vaccine, Live, Non-Replicating (trade name JYNNEOS) is approved by FDA for the prevention of smallpox and mpox disease in adults 18 years of age and older determined to be at high risk for smallpox or mpox infection. JYNNEOS is licensed for subcutaneous injection of 2 doses of 0.5 ml given at an interval of 28 days, based on a comparable immune response to replicating vaccinia vaccine (trade name ACAM2000) in a pivotal randomized clinical trial.[i] 

Throughout 2022 supplies of JYNNEOS are expected to be limited. The number of doses at the standard 0.5 ml volume are insufficient to protect prioritized populations at risk of contracting mpox during the current epidemic.   

On August 9, 2022, FDA issued Emergency Use Authorization (EUA) for intradermal injection of doses of 0.1 ml as an alternative to subcutaneous injection for adults 18 years and older, similarly given as a 2-dose series at an interval of 28 days. Subsequent guidance from CDC endorses intradermal vaccination of adults against mpox. Especially while supplies remain scarce, California Department of Public Health (CDPH) recommends properly trained vaccinators in California administer intradermal doses of JYNNEOS to as many age eligible adults and who are able to receive the vaccine. Doing so will help California maximize the overall risk reduction of severe mpox for as many adults at risk as possible. Training resources on intradermal vaccination are posted in the EZIZ Mpox Resources and the CDC JYNNEOS Vaccine page. Use of low dead space syringes and needles for intradermal injection will also help to maximize the number of available doses. 

Prospective vaccinees should be counseled about the possibility of prolonged swelling at the site of injection after vaccination, which is a common side effect regardless of route of administration but will likely occur in a higher proportion of vaccinees receiving intradermal doses. 

During this outbreak, the alternative regimen (intradermal route (PDF)) is preferred, but the JYNNEOS vaccine may be administered subcutaneously using the standard regimen (subcutaneous route (PDF)). People of any age with a history of developing keloid scars and individuals younger than 18 years of age should receive the vaccine via the subcutaneous route. Patients with concerns about intradermal administration due to potential stigma or other personal reasons should be offered subcutaneous doses. CDC recommends that health care providers have both subcutaneous and intradermal vaccine administration options available on site so that those unable or unwilling to receive the intradermal regimen, can receive the subcutaneous regimen.  An updated CDPH JYNNEOS vaccine screening (PDF) checklist (also available in Spanish(PDF)) can be used to check for history of keloids.

As new clinical data evolves on the level of protection provided by JYNNEOS in the current outbreak, CDPH considers vaccination an important intervention to reduce severity of illness and will continue to monitor emerging data in its ongoing evaluation of its interim guidance. CDPH recommends individuals continue to also consider other preventive measures to reduce risk of mpox infection.

Rationale for the interim guidance: 

Data in support of the EUA and CDC guidance include a National Institute of Health (NIH)-sponsored trial of healthy men and women ages 18-38 years that compared subcutaneous administration of a 0.5ml dose (n=167) against intradermal vaccination of a 0.1ml dose (n=192).[ii] Initial immune response after the first JYNNEOS and second dose were similar between the two groups, whether measured by plaque reduction neutralization tests or ELISA. In a prior preliminary trial (n=10-12 per arm) comparing routes and doses[iii], levels of binding and neutralizing antibodies to vaccinia were comparable to the current dose of subcutaneous JYNNEOS vaccination after intradermal vaccination of 10% of the current dose. 

Intradermal immunization can result in swelling at the site of injection more frequently than after subcutaneous or intramuscular immunization, occurring in nearly all trial participants who received intradermal mpox vaccine[ii], and many who received licensed intradermal seasonal influenza vaccine.[iv] 36% of trial participants who received intradermal mpox vaccine had mild injection site induration, irritation, or discoloration lasting at least 6 months[ii]The proportion of trial recipients with systemic reactions was similar between intradermal and subcutaneous vaccination after dose 1 (60% vs 51%) and dose 2 (44% vs. 45%)[ii]. 

Current experience with intradermal injection may vary by clinical setting. Proper injection technique can minimize unintentionally underdosing, leakage or subcutaneous injection, that could reduce the level of antibody generated by a dose and require revaccination.

[i] Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox (

[ii] Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects (

[iii] Safety and Immunogenicity of Modified Vaccinia Ankara (ACAM3000): Effect of Dose and Route of Administration (PDF) (

[iv] Package-Insert---Fluzone-Intradermal (PDF) (

Page Last Updated :