September 5, 2024

ACIP Evidence to Recommendations for Use of JYNNEOS (orthopoxvirus) Vaccine Primary Series for Healthcare Personnel (Policy Question 2)

The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.

Summary

Question: Should JYNNEOS be recommended, based on shared clinical decision-making, for persons who are at risk for occupational exposure to orthopoxviruses*?

Population: Persons who are at risk for occupational exposure to orthopoxviruses

Intervention: Vaccination with JYNNEOS

Comparison(s): Vaccination with ACAM2000

Outcome: 1) Prevention of disease 2) Severity of disease 3) Severe adverse events 4) Myo-/peri-carditis

_{*For some populations, a subset of persons may benefit from receiving the vaccine but the entire population would not. For those persons, ACAM2000 is currently offered permissively as needed but not for the entire population. Examples of persons for whom this shared clinical decision-making may apply are persons who administer ACAM2000 to a large number of persons, persons who currently treat ACAM2000 clinical trial participants or investigate monkeypox outbreaks}

Background

In September 2019, FDA approved JYNNEOS Smallpox and Monkeypox Vaccine, Live, Non-Replicating, for the prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. Licensure of this vaccine means that there are now 2 vaccines for prevention of smallpox that are licensed in the US, the other vaccine being ACAM2000. JYNNEOS is the only currently FDA-approved vaccine with an indication that explicitly includes prevention of monkeypox disease. It is a replication-deficient modified vaccinia Ankara, administered subcutaneously in 2 doses that are given 28 days apart, does not produce a cutaneous reaction or “take” and there is no risk of inadvertent inoculation or autoinoculation. Serious adverse events like progressive vaccinia and eczema vaccinatum are not expected to occur with JYNNEOS; this is because these have occurred with previous orthopoxvirus vaccines secondary to uncontrolled viral replication and there is no risk for that with JYNNEOS. Cardiac adverse events like myopericarditis are believed to be fewer and FDA assessed effectiveness by comparing the immunologic response to ACAM2000 and deemed it non-inferior.

CDC has received multiple inquiries from federal agencies, occupational health clinics, and vaccinees inquiring about when JYNNEOS will be available specifically because they would like to receive JYNNEOS (instead of ACAM2000) because of the favorable profile outlined above.

Problem

Criteria	Work Group Judgements	Evidence	Additional Information
Is the problem of public health importance?	Yes	It is important to have more than oen vaccine available for prevention of orthopoxviruses and this would be a second that is currently available Public health authorities are being asked when JYNNEOS will be available because there is interest in receiving it instead of ACAM2000. There is unpublished data from DRC that JYNNEOS is preferred to ACAM2000; we anticipate there will be many requests in the U.S. for JYNNEOS as well.

Benefits and Harms

Criteria	Work Group Judgements	Evidence	Additional Information
How substantial are the desirable anticipated effects?	Small	Small benefit of JYNNEOS compared to aCAM per GRADE table.	Most people within this population are at low risk for orthopoxviruses but some may benefit No disease has been observed among this population of people (i.e., persons administering ACAM2000, treating ACAM2000 clinical trial patients, or investigating monkeypox outbreaks); so the risk is believed to be low Similar to the ACAM2000 recommendations, this option enables persons within this population who would benefit from vaccination to receive it
How substantial are the undesirable anticipated effects?	Minimal	No known harms; however, the Evidence table could not adequately assess adverse events given the low number of subjects and other study limitations
Do the desirable effects outweigh the undesirable effects?	Favors interventional	Benefits listed above are large and the harms are minimal
What is the overall certainty of this evidence for the critical outcomes?	Effectiveness of the intervention: Low	The Evidence table shows low to very low certainty

Values

Criteria	Work Group Judgements	Evidence	Additional Information
Does the target population feel that the desirable effects are large relative to undesirable effects?	Probably yes	There is no research data to evaluate this but it is believed that some members of the population will be interested in vaccination or at least having the option of being vaccinated; when patient have been admitted for disseminated vaccinia etc. in the past, healthcare workers were anxious; this option enables those who want to be vaccinated to be vaccinated
Is there important uncertainty about or variability in how much people value the main outcomes?	Probably not important uncertainty or variability	Because of the low risk, many persons within this population may opt to not be vaccinated; others, however, may (for the factors discussed previously) opt to be vaccinated This recommendation would, however, allow alignment with the permissive recommendation for ACAM2000 for this same population

Acceptability

Criteria	Work Group Judgements	Evidence	Additional Information
Is the intervention acceptable to key stakeholders?	Yes	Ease of finding provider No risk of transmission to others No absences from work to travel to a provider who can give the vaccine; any provider can administer a subcutaneous injection Less pain and no concerns for auto-inoculation or infection transmission to others, particularly to immunocompromised persons and those with eczema Stakeholders are expected to be supportive of some members of this population choosing vaccination	Although there is no research evidence available, orthopoxvirus recipients have repeatedly reached out to CDC and the product sponsor to ask about the availability of the vaccine suggesting that the convenience associated with the vaccine makes the booster dose acceptable.

Resource Use

Criteria	Work Group Judgements	Evidence	Additional Information
Is the intervention a reasonable and efficient allocation of resources?	Yes	JYNNEOS, like ACAM2000, would be provided from HHS’ Strategic National Stockpile (SNS) free-of-cost to the patient The cost of the clinic appointments would presumably be covered by occupational health and stakeholders would be supportive

Equity

Criteria	Work Group Judgements	Evidence	Additional Information
What would be the impact on health equity?	Increased	There would be decreased costs and challenges for those who have to travel to identify a provider to provide the vaccine since occupational health could administer the subcutaneous injection

Feasibility

Criteria	Work Group Judgements	Evidence	Additional Information
Is the intervention feasible to implement?	Yes	No research identified Potentially more in-person clinic visits with JYNNEOS compared to ACAM2000 but less difficulty getting on a vaccination schedule because more providers willing to administer a subcutaneous injection

Balance of consequences

Desirable consequences probably outweigh undesirable consequences in most settings

Is there sufficient information to move forward with a recommendation? Yes.

Policy options for ACIP consideration

ACIP recommends the intervention

Final deliberation and decision by the ACIP

Final ACIP recommendation

Additional ACIP considerations

View the complete list of EtR Frameworks‎‎‎

List of Evidence to Recommendations Framework Tables