About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Summary
Question: Does ACIP recommend the 2-dose JYNNEOS vaccine seriesA for persons aged 18 years and older at risk of mpox during an mpox outbreak?B
Background
Mpox has historically been a rare, sometimes life-threatening illness endemic to certain parts of West and Central Africa. It is caused by monkeypox virus (an orthopoxvirus) and divided into two clades: clade I (endemic to central Africa) and clade II (endemic to west Africa). It can spread from infected animals to people and then person-to-person spread can occur primarily via skin-to-skin contact with infected bodily fluids, respiratory secretions, or fomites. There have been three previous outbreaks of mpox in the US: a large outbreak of 47 cases occurred in 2003 linked to pet prairie dogs cohoused with infected small mammals from Ghana, another two outbreaks occurred in 2021 among two separate travelers from Nigeria. The first mpox case from the global outbreak that started in 2022 was detected in the United Kingdom in May 2022. This quickly spread to many countries and is primarily affecting gay, bisexual, and other men who have sex with men. It is associated with person-to-person spread via close skin-to-skin contact including sex.
Problem
| Criteria | Work Group Judgments | Research Evidence | Additional Information |
|---|---|---|---|
| How substantial are the desirable anticipated effects? | Yes | Human mpox outbreaks have occurred multiple times in the United States. In 2003, pet prairie dogs cohoused with small African mammals that led to 47 mpox cases detected. Two separate outbreaks occurred of people traveling from Nigeria to the US in Summer and Fall of 2021. Travel associated cases have also been detected in the United Kingdom in 2019 and 2020, with one case of secondary transmission. In 2022, a global outbreak of mpox began that resulted in >30,000 cases. Severe manifestations have occurred, primarily in severely immunocompromised people. | McCollum AM, Shelus V, Hill A, et al. Epidemiology of Human Mpox — Worldwide, 2018–2021. MMWR Morb Mortal Wkly Rep 2023;72:68–72
Hobson G, Adamson J, Adler H, Firth R, Gould S, Houlihan C, Johnson C, Porter D, Rampling T, Ratcliffe L, Russell K, Shankar AG, Wingfield T. Family cluster of three cases of monkeypox imported from Nigeria to the United Kingdom, May 2021. Euro Surveill. 2021 Aug;26(32):2100745. Reynolds MG, Yorita KL, Kuehnert MJ, Davidson WB, Huhn GD, Holman RC, Damon IK. Clinical manifestations of human monkeypox influenced by route of infection. J Infect Dis. 2006 Sep 15;194(6):773-80. |
Benefits and harms
| Criteria | Work Group Judgments | Evidence | Additional Information |
|---|---|---|---|
| How substantial are the desirable anticipated effects? | Large |
Vaccine performance: One study using ob体育 surveillance data compared the mpox incidence between vaccinated and unvaccinated persons in 43 U.S. jurisdictions. It showed mpox incidence among unvaccinated was 7.4 (95% CI = 6.0-9.1) times higher than persons who received only 1 dose of JYNNEOS vaccine ≥ 14 days earlier, and 9.6 (95% CI = 6.9-13.2) times higher than persons who received dose 2 ≥ 14 days earlier.
Population-based, adjusted measures of vaccine effectiveness (VE) using electronic medical records: Nationwide, U.S. case-control study with 1:4 ratio of cases matched to controls; adjusted VE (adjusted for age, race/ethnicity, social vulnerability index score, presence or absence of immunocompromising conditions) was 35.8% (95% CI: 22.1-47.1%) for one dose and 66.0% (95% CI: 47.7-78%) for 2 doses, regardless of vaccination route
Population-based, adjusted measures of VE using case-control studies: 1) Case-control study of adult MSM (18-49 years of age) in 12 U.S. jurisdictions; adjusted (adjusted for age, race/ethnicity, self-reported immunocompromise) VE was 76% (95% CI: 48-49%) for 2 doses (interim results) 2) New York State case-control study of adult male mpox cases matched to sexually transmitted infection controls; adjusted VE (adjusted for week of diagnosis, region, age, race/ethnicity) was 68% (95% CI: 25-86%) for one dose and 89% (95% CI: 44-98%) for 2 doses (preliminary results)
PEP effectiveness and infections following single dose: NYC: Cohort study of individuals with high-risk exposure; VE was 78% (CI 50-91) with PEP 0-14 days after last exposure and 73% (CI 31-91) with PEP 0-14 days after first exposure using multivariable regression. However when using Target trial methodology, VE was 19% (CI -54-57) with PEP 0-14 days after last exposure and -7% (CI -144-53) with PEP 0-14 days after first exposure.
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The design of each of these studies was different. However, the data as well as real-world surveillance data indicate that the 2-dose JYNNEOS vaccine series prevents or reduces severity of many infections during the clade II outbreak that began in 2022. Because mpox spreads through close person-to-person contact (e.g., to exposed lesions or respiratory secretions), including during sex, vaccination of at-risk persons may have a herd immunity effect.
Payne AB, Ray LC, Cole MM, et al. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons — 43 U.S. Jurisdictions, July 31–October 1, 2022. MMWR Morb Mortal Wkly Rep 2022;71:1560–1564. Deputy NP, Deckert J, Chard AN, Sandberg N, Moulia DL, Barkley E, Dalton AF, Sweet C, Cohn AC, Little DR, Cohen AL, Sandmann D, Payne DC, Gerhart JL, Feldstein LR. Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States. N Engl J Med. 2023 Jun 29;388(26):2434-2443. Dalton AF, Diallo AO, Chard AN, et al. Estimated Effectiveness of JYNNEOS Vaccine in Preventing Mpox: A Multijurisdictional Case-Control Study — United States, August 19, 2022–March 31, 2023. MMWR Morb Mortal Wkly Rep 2023;72:553–558 Rosenberg ES, Dorabawila V, Hart-Malloy R, et al. Effectiveness of JYNNEOS Vaccine Against Diagnosed Mpox Infection — New York, 2022. MMWR Morb Mortal Wkly Rep 2023;72:559–563. Rosen JB, Arciuolo RJ, Pathela P, Boyer CB, Baumgartner J, Latash J, Malec L, Lee EH, Reddy V, King R, Edward Real J, Lipsitch M, Zucker JR. JYNNEOS™ effectiveness as post-exposure prophylaxis against mpox: Challenges using real-world outbreak data. Vaccine. 2024 Jan 25;42(3):548-555. |
| How substantial are the undesirable anticipated effects? | Small | During May 22, 2022 to January 13, 2023, a total of 1,125, 168 JYNNEOS vaccine doses were administered across the U.S. ob体育 monitored JYNNEOS safety using 3 surveillance systems (VAERS, V-safe, and the Vaccine Safety Datalink, VSD). Most common Adverse Events reported were nonserious and included injection site reactions, consistent with prelicensure studies. These were reported at similar rates for doses received by intradermal and subcutaneous administration. Serious adverse events were rare among adults. |
Duffy J, Myers TR, Marquez P, Rouse D, Brown H, Zhang B, Shay DK, Moro PL. JYNNEOS Vaccine Safety Surveillance During the 2022 Mpox Outbreak Using the Vaccine Adverse Event Reporting System and V-safe, United States, 2022 to 2023. Sex Transm Dis. 2024 Aug 1;51(8):509-515.
Duffy J, Yih WK, Walton K, DeSilva MB, Glanz JM, Hambidge SJ, Jackson LA, Klein NP, Lewin BJ, Naleway AL, Sundaram ME, Maro JC, Weintraub E. JYNNEOS vaccine safety surveillance in the vaccine safety datalink during the 2022 mpox outbreak in the United States. Infection. 2024 Nov 20:10.1007/s15010-024-02428-1.
Duffy J, Marquez P, Moro P, Weintraub E, Yu Y, Boersma P, Donahue JG, Glanz JM, Goddard K, Hambidge SJ, Lewin B, Lewis N, Rouse D, Shimabukuro T. Safety Monitoring of JYNNEOS Vaccine During the 2022 Mpox Outbreak - United States, May 22-October 21, 2022. MMWR Morb Mortal Wkly Rep. 2022 Dec 9;71(49):1555-1559.
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| Do the desirable effects outweigh the undesirable effects? | Favors intervention |
The benefits were deemed large and the harms, small. For this reason, the desirable effects of vaccination with the JYNNEOS series outweigh the undesirable effects.
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Values
| Criteria | Work Group Judgments | Evidence | Additional Information |
|---|---|---|---|
| Does the target population feel that the desirable effects are large relative to undesirable effects? | Probably yes |
The target population may differ depending on the outbreak and the population impacted. Data was collected during the mpox outbreak that began in 2022:
Populations at highest risk during the global clade IIb outbreak that began in 2022 were concerned about mpox: 1) In August 2022, 53.1% of American Men’s Internet Survey (AMIS) respondents had concerns about getting mpox. 2) During October-December, an AMIS survey showed that those with high mpox concern had 3.5 times odds of being vaccinated.
Interest in vaccine high: During August-November 2022, >85% of respondents in the American Transformative HIV Study (AMETHYST) were interested in vaccine. During August-December 2022, 50% of Porter-Novelli survey responders who identified as LGBTQ+ felt that vaccination is important to protect from mpox. During October to November 2022, >70% of MSM in a San Francisco survey of persons experiencing homelessness reported that they would accept or have accepted vaccination.
Other populations impacted during future outbreaks are similarly expected to value vaccination.
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| Is there important uncertainty about or variability in how much people value the main outcomes? | Possibly important uncertainty or variability | During the 2022 mpox outbreak, willingness to be vaccinated was dynamic, and dependent on perceived vulnerabilities. There were clear demands for JYNNEOS vaccination but many remain unvaccinated for unclear reasons (although a presumption that the outbreak is over was believed to be at play). Demographics of future outbreaks are unclear so it is unknown if values expressed by the population most affected by the 2022 mpox outbreak can be extrapolated to all other populations |
Acceptability
| Criteria | Work Group Judgments | Evidence | Additional Information |
|---|---|---|---|
| Is the intervention acceptable to key stakeholders? | Yes |
SermoC is an online community of >1.3 million clinician. During July 31-August 1, 2022, survey results of U.S. clinicians (n= 415) showed 69% felt U.S. without enough mpox vaccine to handle the outbreak. On September 12, 2022, the survey among 62 U.S. clinicians showed 66% had treated at least one patient with mpox, 76% knew where a patient could get the JYNNEOS vaccination, and 86% wanted to be able to provide vaccination in their office.
During the peak of the outbreak, health departments requested JYNNEOS and organized vaccination campaigns. Jurisdictions had ordered 70% of their allocations by February 2023.
A vaccine equity pilot program was established. This enabled jurisdictions to request more than their allotted amount of JYNNEOS vaccine. It was established to support innovative ways to address vaccination disparities, encourage vaccination coordination between health departments and community-based organizations, and promote innovation to strengthen existing vaccination infrastructure. A total of 28 programs were established involving 15 jurisdictions and ~25,000 doses were administered as of February 2023.
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Resource use
| Criteria | Work Group Judgments | Evidence | Additional Information |
|---|---|---|---|
| Is the intervention a reasonable and efficient allocation of resources? | Varies |
JYNNEOS was available free of cost from HHS’ Strategic National Stockpile at the time of the vote. Vaccines are considered a good use of resources during outbreaks.
There were costs and challenges during the 2022 mpox outbreak in the United States associated with mobile, pop-up vaccination sites. This is an outbreak recommendation; therefore, cost effectiveness analysis was not performed for this vote.
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Overall, there are uncertainties depending on the type of outbreak that occurs. In the future, when JYNNEOS is not available via HHS’ Strategic National Stockpile, but rather commercially, there could be additional considerations. |
Equity
| Criteria | Work Group Judgments | Evidence | Additional Information |
|---|---|---|---|
| What would be the impact on health | Probably increased |
No groups or settings are believed to be disadvantaged by the recommendation for JYNNEOS during outbreaks. The effectiveness is believed to be the same for all immunocompetent persons. Implementation to assure equitable access will be important, particularly among persons who are at high risk for severe outcomes. An ACIP recommendation might facilitate broad acceptance of vaccination (e.g., by insurance companies, health departments) because an endorsement by ACIP occurs after rigorous review of the evidence.
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Equity is believed to increase as a result of the recommendation because those who are at-risk for mpox and vaccinated will have favorable outcomes (similar to those who are not at-risk for mpox). |
Feasibility
| Criteria | Work Group Judgments | Evidence | Additional Information |
|---|---|---|---|
| Is the intervention feasible to implement? | Yes |
During the 2022 mpox outbreak, many vaccine campaigns were conducted in communities, at events, and within public health facilities, indicating feasibility for future outbreaks. These can be integrated into providers’ practices because standing orders are available, immunization information systems requirements for reporting vaccinations was the same as for COVID-19 vaccines (and people are familiar) and JYNNEOS can be stored in refrigerators for 8 weeks. Because the route of administration is subcutaneous, a wide range of people can administer JYNNEOS vaccines.
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The workgroup felt that JYNNEOS vaccination is probably sustainable during outbreaks but that vaccine access is an important consideration: access should be increased and convenient and not associated with stigma. During an outbreak, there should be strong ties with community-based organizations, support at vaccination events, engagement with trusted messengers, and access to vaccine in rural areas. |
Balance of consequences
Desirable consequences clearly 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
Draft recommendation (text)
ACIP recommends the 2-dose JYNNEOS vaccine seriesD for persons aged 18 years and older at risk of mpox during an mpox outbreakE
Final ACIP recommendation
ACIP recommends the intervention.
- Dose 2 should be administered 28 days after dose 1
- Public health authorities will determine whether there is an mpox outbreak; a single case may be considered an mpox outbreak at the discretion of public health authorities. Other circumstances in which a public health response may be indicated include ongoing risk of introduction of mpox into a community due to disease activity in another geographic area
- Dose 2 should be administered 28 days after dose 1
- Public health authorities will determine whether there is an mpox outbreak; a single case may be considered an mpox outbreak at the discretion of public health authorities. Other circumstances in which a public health response may be indicated include ongoing risk of introduction of mpox into a community due to disease activity in another geographic area.