Smallpox and MPX Vaccine, Live, Non-Replicating (trade name JYNNEOS) is approved by FDA for the prevention of smallpox and MPX disease in adults 18 years of age and older determined to be at high risk for smallpox or MPX 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 MPX 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 MPX. 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 as who are able to receive the vaccine via an intradermal administration. Doing so will help California maximize the overall risk reduction of severe MPX for as many adults at risk as possible. Training resources on intradermal vaccination are posted in the EZIZ MPX Resources 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 local inflammation 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.
In order to maximize the number of individuals that can benefit from JYNNEOS vaccine during this epidemic, CDPH recommends intradermal administration with exceptions for subcutaneous use noted in current CDC guidance such as individuals with a history of developing keloid scars or who are younger than 18 years of age. An updated CDPH JYNNEOS vaccine screening form (also available in Spanish) can be used to check for history of keloids.
As there are limited clinical data yet 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 consider other preventive measures to reduce risk of MPX infection.
Rationale for the interim guidance:
Data in support of the EUA and CDC guidance include an 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 immunogenicity 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 local inflammation at the site of injection more frequently than after subcutaneous or intramuscular immunization, occurring in nearly all trial participants who received intradermal MPX vaccine[ii], and many who received licensed intradermal seasonal influenza vaccine.[iv] 36% of trial participants who received intradermal MPX vaccine had mild injection site induration, erythema, 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 inadvertent underdosing, leakage or subcutaneous injection, that could reduce the level of antibody generated by a dose and require revaccination.