September 9, 2024

ACIP Evidence to Recommendations for Use of JYNNEOS (orthopoxvirus) Vaccine Booster Every 2 Years (Policy Question 3)

ACIP recommends booster doses of JYNNEOS every 2 years after the primary for persons who are at continued risk for occupational exposure to more virulent orthopoxviruses like variola virus or monkeypox.

Summary

Question: Should persons who are at continued risk* for occupational exposure to more virulent orthopoxviruses like variola virus or monkeypox receive booster doses of JYNNEOS every 2 years after the primary JYNNEOS series

Population: Persons who are at risk for occupational exposure to smallpox or monkeypox

Intervention: Booster with JYNNEOS every 2 years

Comparison(s): No booster

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

ACAM2000 is licensed for prevention of smallpox and the package insert recommends booster dose every 3 years for persons at continued risk. 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).

JYNNEOS is licensed for prevention of both smallpox and monkeypox disease. The package insert describes dosage and administration of the primary vaccination series but does not indicate whether a booster dose should be given or how frequently, possibly because this vaccine has only recently been licensed. However, there is non-randomized trial data that shows boostability of the primary series 2 years after completion of the primary series indicating that the 2 year time interval is appropriate. For virulent pathogens like smallpox and monkeypox, it is important to recommend a conservative interval for booster doses until more data is available.

Problem

Criteria	Work Group Judgements	Evidence	Additional Information
Is the problem of public health importance?	Yes	Smallpox and monkeypox are highly virulent pathogens; vaccination ensures that even if unintentional breaches in personal protective equipment and other safeguards were to occur, workers have continued immunity. Increasing number of laboratories work with monkeypox virus (e.g., primate laboratories)

Benefits and Harms

Criteria	Work Group Judgements	Evidence
How substantial are the desirable anticipated effects?	Large	Smallpox and monkeypox are highly virulent pathogens Boosters at recommended intervals provide reassurance if inadvertent exposures occur
How substantial are the undesirable anticipated effects?	Minimal	No known harms
Do the desirable effects outweigh the undesirable effects?	Favors interventional	Benefits listed above are moderate 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 nearly every outcome pertaining to this PICO question and for one outcome (severity of disease) there is no data.

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 a booster dose is expected to be interpreted as having large desirable effects relative to undesirable effects. The desirable effects are “protection” from inadvertently acquiring virulent pathogens and there are no undesirable effects.
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 of persons who work with smallpox mandate booster doses.

Acceptability

Criteria	Work Group Judgements	Evidence	Additional Information
Is the intervention acceptable to key stakeholders?	Yes	Since there is data (albeit limited) to indicate boostability 2 years after the primary series, recommending booster every 2 years (i.e., 1 year sooner than what is recommended for ACAM2000) is expected to be acceptable to stakeholders. Most clinicians are not experienced in (or willing to) administer ACAM2000 because it is not the typical “shot”; administration involves repeated pricks from a bifurcated needle that was dipped in vaccine solution. Clinician follow-up is needed ~7 days later to ensure induration (i.e., “take”) that confirms successful vaccination. Because of this, it can be difficult for some persons to find providers. JYNNEOS is administered subcutaneously, a technique that most clinicians are skilled and experienced with performing. Interested patients will not have difficulty finding a provider to administer this vaccine for this reason.	With ACAM2000, some persons in this population do have difficulty finding a provider to administer the vaccine even though any provider can request and administer it and there are reputable online tutorials about administration (including from CDC) 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 For many recipients, employers absorb the clinic costs (e.g., occupational health). For some, there may be costs associated with clinic appointments for booster doses. More research is needed but these costs are likely be a reasonable and efficient allocation of resources.

Equity

Criteria	Work Group Judgements	Evidence	Additional Information
What would be the impact on health equity?	Probably no impact	If not absorbed by the employer, the vaccine recipient could incur costs from the clinic appointment; however no other costs are expected for the vaccinee because it is provided by the SNS at no cost and for many recipients, the employer will likely absorb costs.

Feasibility

Criteria	Work Group Judgements	Evidence	Additional Information
Is the intervention feasible to implement?	Probably yes	No research evidence identified It may take some effort to plan for booster doses but since nearly every provider can administer a subcutaneous vaccine, scheduling can be with a wide variety of providers which likely makes it feasible

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