September 5, 2024

ACIP Evidence to Recommendations for Use of JYNNEOS (orthopoxvirus) Vaccine Heterologous for Those Who Received ACAM2000 Primary Series (Policy Question 5)

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

Summary

Question: Should persons who are at continued risk* for occupational exposure to orthopoxviruses, and who received an ACAM2000 primary vaccination, receive a booster dose of JYNNEOS as an option to a booster dose of ACAM2000?

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

Intervention: Booster with JYNNEOS

Comparison(s): Booster with ACAM2000

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

_{*Orthopoxvirus and healthcare worker response teams designated by appropriate public health and antiterrorism authorities are not at “continued risk” because they are vaccinated for the purposes of preparedness.}

Background

The ACIP recommends booster doses of ACAM2000 every 3 years for persons at occupational risk for virulent replicating orthopoxviruses (e.g., variola virus and monkeypox) and at least every 10 years for persons at occupational risk for less virulent orthopoxviruses (e.g., cowpox and vaccinia virus). Vaccination with ACAM2000 has contraindications (e.g., being a household contact of a person with eczema), is believed to have more serious adverse events (including myopericarditis), and requires infection control measures because contact with the vaccination site can result in auto-inoculation or infection to others. Additionally, the vaccination technique can be painful and a smaller number of providers are willing to administer it compared to subcutaneous vaccines like JYNNEOS.

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) for booster vaccines even though they received ACAM2000 primary series.

Problem

Criteria	Work Group Judgements	Evidence	Additional Information
Is the problem of public health importance?	Yes	Health authorities are being asked when JYNNEOS will be available so that persons previously receiving ACAM2000 can switch to JYNNEOS. Some laboratory directors have indicated that their entire lab will switch to JYNNEOS once it becomes available as long as the ACIP recommendations overtly allow for this. 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?	Large	Logistics for receiving vaccine and maintaining the vaccine site are easier Comparable “protection” to ACAM2000 presumed JYNNEOS is not a live virus so there is no potential for spread to others There are few contraindications
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: Very low	The Evidence table shows very low certainty for every outcome pertaining to this PICO question

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 persistent immunity Employers are expected to favor the convenience of JYNNEOS vaccinations and some laboratory directors have indicated that their entire laboratory may be favor JYNNEOS if given the option

Acceptability

Criteria	Work Group Judgements	Evidence	Additional Information
Is the intervention acceptable to key stakeholders?	Yes	Ease of difficulty 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 appointment would be the same as that for ACAM2000 vaccination

Equity

Criteria	Work Group Judgements	Evidence	Additional Information
What would be the impact on health equity?	Probably increasedt	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 Same number of clinic visits as with ACAM2000

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