September 5, 2024

ACIP Evidence to Recommendations for Use of JYNNEOS (orthopoxvirus) Vaccine Primary Series for Research, Clinical Laboratory, and Response Team Personnel (Policy Question 1)

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

Summary

Question: Should JYNNEOS® be recommended for research and clinical laboratory personnel performing diagnostic testing for orthopoxviruses* and for designated response teams^# at risk for occupational exposure to orthopoxviruses?

Population: Clinical laboratory personnel performing diagnostic testing for orthopoxviruses and designated response teams

Intervention: Vaccination with JYNNEOS®

Comparison(s): Vaccination with ACAM2000

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

_{*Clinical laboratory personnel who perform routine chemistry, hematology, and urinalysis testing, including for suspect patients with orthopoxvirus infections, are not included in this recommendation as their risk for exposure is very low}

_{^#Public health authorities, at their own discretion, may approve a cohort of healthcare and/or public health personnel to receive primary vaccination against orthopoxviruses for preparedness purposes (i.e., in the event of a smallpox or monkeypox outbreak)}

_{[Note: Clinical laboratory personnel who perform routine chemistry, hematology, and urinalysis procedures are not recommended to be vaccinated with ACAM2000 or JYNNEOS because their risk of occupational exposure to orthopoxviruses is very low]}

Background

In September 2019, FDA approved JYNNEOS®, a live replication-deficient modified vaccinia Ankara, 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. With the licensure of this vaccine, there are now 2 vaccines available in the United States for the prevention of orthopoxviruses; the other vaccine is ACAM2000, a live replicating vaccinia virus vaccine that is derived from a clonal isolate of Dryvax, the New York City Board of Health strain widely used during the smallpox eradication campaign. JYNNEOS® differs from ACAM2000 in several ways: JYNNEOS® is administered subcutaneously in 2 doses that are given 28 days apart, does not produce a cutaneous reaction or “take”, and does not carry risks for inadvertent inoculation or autoinoculation. Serious adverse events like progressive vaccinia and eczema vaccinatum are not expected to occur with JYNNEOS®; this is because the uncontrolled viral replication that occurred with previous orthopoxvirus vaccines (i.e., live, replicating vaccines) does not happen with JYNNEOS® (live, non-replicating vaccine). Cardiac adverse events like myopericarditis are believed to be fewer with JYNNEOS®. FDA assessed effectiveness by comparing its immunologic response to that of 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. Because of the favorable profile outlined above, there is specific interest in receiving doses of JYNNEOS® (instead of ACAM2000) as the recommended boosters even though ACAM2000 was the vaccination administered for the primary series for a vaccinee.

Problem

Criteria	Work Group Judgements	Evidence	Additional Information
Is the problem of public health importance?	Yes	It is important to have more than one 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. 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
How substantial are the desirable anticipated effects?	Small	Evidence table for outcome A, prevention of disease, suggests that there is a small benefit of JYNNEOS compared to ACAM2000 for prevention of infection Found to be non-inferior to ACAM2000 for immunogenicity by FDA resulting in licensure JYNNEOS is not a replicating virus so there is no potential for spread to others
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 There are few contraindications and believed to be fewer serious adverse events
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: Moderate	The Evidence table shows moderate certainty for prevention of disease and either low (for serious adverse events and myopericarditis) or very low (severity of disease) outcomes

Values

Criteria	Work Group Judgements	Evidence	Additional Information
Does the target population feel that the desirable effects are large relative to undesirable effects?	Yes	There is no research data to evaluate this but the target population has been making multiple requests for this vaccine
Is there important uncertainty about or variability in how much people value the main outcomes?	Probably not important uncertainty or variability	Although there is no research identified, stakeholders are expected to value immunity and the 2-dose JYNNEOS was found to be non-inferior to ACAM2000 by FDA for immunogenicity There are 2-doses over 28 days needed for JYNNEOS but only one vaccination visit for ACAM2000 and an individual will not be considered fully vaccinated until later for JYNNEOS than ACAM2000

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	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 could potentially be more for JYNNEOS because two in-person clinic visits are needed. In the case of ACAM2000, only one clinic visit is needed for vaccination but a second ~7 days later is recommended to confirm the cutaneous reaction, i.e., “take”, confirming vaccination; this, however, can potentially occur through telemedicine and does not require an in-person visit	Some clinics have patients return for in-person clnic appointments on days 3, 7 etc. So there may be multiple clinical appointments for ACAM2000 even though only one appointment for the vaccine.

Equity

Criteria	Work Group Judgements	Evidence	Additional Information
What would be the impact on health equity?	Increased	For some vaccine recipients, the cost of the clinic appointment is absorbed by the employer; for others, it is not. There would be no change in those costs. However, there would be decreased costs and challenges for those who have to travel to identify a provider to provide the vaccine.

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