September 9, 2024

ACIP Evidence to Recommendations for Use of JYNNEOS (orthopoxvirus) Vaccine Booster Every 10 Years (Policy Question 4)

ACIP recommends persons who are at continued risk* for occupational exposure to replication competent orthopoxviruses like vaccinia or cowpox receive booster doses of JYNNEOS after the primary JYNNEOS series.

Summary

Question: Should persons who are at continued risk* for occupational exposure to replication competent orthopoxviruses like vaccinia or cowpox receive booster doses of JYNNEOS after the primary JYNNEOS series

Population: Persons who are at risk for occupational exposure to replication competent orthopoxviruses like vaccinia or cowpox.

Intervention: Booster with JYNNEOS

Comparison(s): No booster

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

_{*Continued risk refers to “real” risk due to occupational work performed}

Background

The ACIP recommends booster doses of ACAM 2000 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 non-replicating orthopoxviruses (e.g., cowpox and variola). Because ACAM2000 was licensed only for prevention of smallpox disease, the package insert only makes recommendations for persons at continued risk for smallpox disease (i.e., booster doses every 3 years).

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. ACAM2000 and JYNNEOS are not the same vaccine so recommendations about booster frequency for one may not be appliable to the other. However, there is no indication that JYNNEOS is different from ACAM2000 in not needing boosters. Boosters for persons working with non-replicating orthopoxviruses are expected to be less frequent than those for persons working with smallpox and monkeypox.

Problem

Criteria	Work Group Judgements	Evidence	Additional Information
Is the problem of public health importance?	Yes	Increasingly more research laboratories are working with vaccinia vectors resulting in more people at risk for occupational exposure to orthopoxviruses. Public health authorities have been notified of multiple cases of orthopoxviruses among laboratory personnel who were not vaccinated despite work with nonreplicating orthopoxviruses; these infections are associated with morbidity Assurance of long-term immunogenicity is important to preventing illness for persons with persistent risk

Benefits and Harms

Criteria	Work Group Judgements	Evidence
How substantial are the desirable anticipated effects?	Moderate	There is no data to indicate a booster is unnecessary for JYNNEOS; without a formal recommendation, stakeholders may not know to administer JYNNEOS. It is not known when (if ever) there will be data about when a booster should be administered for persons who work with non-replicating orthopoxviruses Boosters at recommended intervals provide increased assurance that the recipient is adequately immunized against disease
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 for one outcome (severity of disease), there is no data available

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	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 is often difficult to find providers to administer ACAM2000. 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. 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?	Probably 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