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Agency for Toxic Substances and Disease Registry National Center for Environmental Health
Centers for Disease Control and Prevention
Evidence to Recommendations Framework: Vaccination with Jynneos for Adolescents at Risk of
Mpox During Outbreaks
Faisal Syed Minhaj, PharmD, MPH Poxvirus and Rabies Branch Centers for Disease Control and Prevention Advisory Committee on Immunization Practices April 15, 2025
•Structure to describe information considering in moving fr om evidence to
ACIP vaccine recommendations
•Provides transparency around the impact of additional fa ctors on
deliberations when considering a recommendation Evidence to Recommendations (EtR) Framework
•Does ACIP recommend the 2-dose* JYNNEOS vaccine serie s for persons 12–
17 years of age at risk of mpox during an mpox outbre ak §?
*Dose 2 administered one month after dose 1 §Public health authorities determine whether there is an mpox outbreak; a single case may be
considered an mpox outbreak at the discretion of pu blic 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. EtR question
Evidence to Recommendation Domains
Question(s) EtR Domain
•Is the problem of public health importance? Public Health Problem
•How substantial are the desirable anticipated effec ts?
•How substantial are the undesirable anticipated eff ects?
•Do the desirable effects outweigh the undesirable e ffects? Benefits and Harms
•Does the target population feel the desirable effec ts are large relative to the
undesirable effects?
•Is there important uncertainty or variability in ho w much people value the
main outcome? Values
•Is the intervention acceptable to key stakeholders? Acceptability
•What would be the impact on health equity? Equity
•Is the intervention feasible to implement? Feasibility
•Is the intervention a reasonable and efficient allo cation of resources? Resource Use
EtR Domain: Public Health Problem
Mpox current situation
Global distribution of confirmed mpox cases, January 1, 2024 – March 26, 2025
Global distribution of confirmed clade I mpox casesJanuary 1, 2024 – April 13, 2025
United States mpox case count and 7-day moving Average – May 2022 through March 2025
Peak Confirmed Daily Cases (7-day average): 467 cases
U.S. mpox case counts in pediatrics, May 2022
through March 2025
Case Count Age
group
92 12-17
17 6-11
23 1-5
15 <1
147 Total
Typical mpox manifestations
Severe manifestations of mpox
Keratitis and conjunctival ulcer
T-wave inversions in inferior and anterolateral lea ds of a patient
with mpox with elevated Tn, SOB, decreased exercise tolerance Encephalomyelitis in a patient with mpox
Severe manifestations from uncontrolled viral replication in severely immunocompromised
Carrubba S. Lancet Infect Dis. 2023 May;23(5):e190-e 197.
Mitjà O. Lancet. 2023 Mar 18;401(10380):939-949.
Are outbreaks of mpox of public health importance?
No Probably no Uncertain Yes
Varies
Probably Yes
EtR Domain: Benefits and Harms
•Adolescent arm met pre-specified criteria for non-inferior ity
-GMT ratio of adolescents to adults was 1.60 (CI 1.3 2, 1.95)
•Vaccine was safe and well tolerated in adolescents
-Solicited systemic and local AEs were similar betwe en adolescents and adults
•Systemic: 74% (CI 69, 79) vs 73% (CI 66, 79)
•Local: 88% (CI 84, 91) vs 91% (CI 87,95)
-Unsolicited related AEs: mainly injection site rela ted
-Dizziness in adolescents is common with vaccine adm inistration in this age group
and is not likely to represent a safety concern Adolescent safety and immunogenicity study summary
•Vaccine Adverse Event Reporting System (VAERS)
-National passive reporting system
•Vaccine Safety Datalink (VSD)
-Large linked healthcare data
•V-safe
-Web-based survey of vaccinees
•Single-patient Emergency Investigational New Drug ( EIND) procedures
-EIND provided vaccine access for individuals <18 ye ars of age prior to EUA
-Collected adverse event information from the vaccin ation provider 28 days after
each dose CDC’s vaccine safety data sources for JYNNEOS
•Vaccine adverse event reporting system (VAERS) 1
-At least 1,245 vaccinees nationwide
-One report of syncope
-Three reports of unspecified mild local and systemi c reactions
•VSD 2
-88 vaccinees
-No adverse events of special interest observed
•V-safe 1
-No participants were <18 years of age
•EIND 3
-57 vaccinees
-21% reported local or systemic reactions. No seriou s adverse events were reported Adverse events among individuals <18 years of age 2022–2023
1) https://pubmed.ncbi.nlm.nih.gov/38647241/ 2) htt ps://pubmed.ncbi.nlm.nih.gov/39565485/ 3) https://p ubmed.ncbi.nlm.nih.gov/36480476/
How substantial are the desirable anticipated effects
Minimal Small Moderate Large
Don’t Know Varies
How substantial are the undesirable anticipated effects
Minimal Small Moderate Large
Don’t Know Varies
Do the desirable effects outweigh the undesirable ef fects?
Favors Intervention Favors Comparison Favors Both
Favors Neither Unclear
EtR Domain: Values
•NIH rapidly completed trial recruitment
•Participants were supportive in participating to help frien ds
•When an outbreak occurred (i.e., 2022 global outbreak) , pediatric close
contacts were vaccinated
•Adolescent Medicine Trials Network for HIV/AIDS Intervent ions (ATN)
youth advisors were surveyed and 12/13 respondents we re supportive of
vaccination
•We do not know what type of outbreak would occur in t he future, and how
adolescents would perceive their risk or acceptability of vaccine Values Considerations
JYNNEOS first doses administered to children 17 yea rs
and younger by sex May 2022 – September 2024
Persons with no age data available were removed fro m the analysis Total first doses Age group
798 12-17
391 6-11
293 1-5
150 <1
1,632 Total
Does the target population feel that the desirable effects are large relative to the undesirable effec ts?
No Probably no Uncertain Yes
Varies
Probably Yes
Is there important uncertainty about or variability in
how much people value the main outcomes?
Important uncertainty or variability Possibly important uncertainty or variability
No known undesirable outcomes
Probably no important uncertainty or variability No important uncertainty or variability
EtR Domain: Acceptability
Data available for acceptability domain
Survey administered to
Adolescent Medicine Trials
Network (ATN) providers Survey of mothers of
adolescents and younger
children
Data available for acceptability domain
Survey administered to
Adolescent Medicine Trials
Network (ATN) providers Survey of mothers of
adolescents and younger
children
ATN V Sites
Eastern U.S.
New Orleans, Louisiana
Tulane University Adolescent Medicine
Atlanta, Georgia
Emory University
San Francisco, California
Bridge HIV, San Francisco Department of Public Health
Los Angeles, California
Children’s Hospital Los Angeles Southern U.S.
New York City, New York
Callen -Lorde Community
Health Center Washington, D.C.
Children’s National Hospital Boston, Massachusetts
The Fenway Institute Houston, Texas
Baylor College of Medicine/ Texas Children’s Hospital Tampa, Florida
University of South Florida
Memphis, Tennessee
St. Jude Children’s Research Hospital Western & Midwestern U.S.
Chicago, Illinois
Adolescent and Young Adult Research (AWAR) @ The CORE Center
•Distributed to clinicians for 1 week in January 2025
•23 providers responded
-21 (91%) treat 12–17-year-olds at risk for mpox
•Among those 21 providers:
-17 (81%) offer vaccines in clinic; 11 (52%) offer mpox vaccine.
-Type of practice:
o19 (90%) university-based;
o1 (5%) FQHC;
o3 (14%) community-based. Survey to Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) providers
N = 21
n (%) Provider Characteristics Provider type
16 (76) Physician
5 (24) NP/PA
Specialty
10 (48) Adolescent medicine
3 (14) Pediatrics
3 (14) Medicine and pediatrics
3 (14) Family medicine
1 (5) Internal medicine
1 (5) Pediatric ID
Survey to ATN providers (N = 21)
If CDC recommended the mpox vaccine for 12–17-year-o lds with risk
factors, would you recommend it for eligible patien ts?
20 1
Yes
No NP/PA, family medicine
What are your concerns about recommending mpox vacc ine for your
eligible 12–17-year-old patients? Survey to ATN providers (N = 21)
20 1
I have no concerns.
I have concerns. “I am not sure if it is effective in preventing mpox”
What are challenges associated with offering the mp ox vaccine in your practice?Survey to ATN providers (N = 21)
N = 21
n (%) Statement
5 (24) There are no challenges in my practice
16 (76) There are challenges
7 (33) It is costly for the clinic to stock
5 (24) Patients are unfamiliar with mpox vaccine
4 (19) I do not know if there are challenges
3 (14) It is costly for patients
2 (10) I do not know how to access mpox vaccine
1 (5) I do not have enough staff trained to administer th is vaccine
1 (5) I am unfamiliar with mpox
1 (5) I am unfamiliar with mpox vaccine
1 (5) Other
Data available for acceptability domain
Survey administered to
Adolescent Medicine Trials
Network (ATN) providers Survey of mothers of
adolescents and younger
children
•Total surveyed: 566
•Unclear the age of all children of the mothers
-Oldest child mean age 9.6 (SD 4.8)
-43% of the population had their oldest child age between 12-17 years
•Timeframe: July 2022
•Variety of household incomes were represented Online survey of Mothers with children ≤18 years
Liu S, Chu H. Patient Educ Couns. 2023 Sep;114:1078 42.
n (%) Variable
510 (90) Receipt of all or some CDC recommended immunizations Race/Ethnicity
59 (10) Black
40 (7.1) Hispanic
19 (3.4) Asian/NHOPI/Native American
439 (78) White
9 (1.6) Other
Number of children
238 (42) One
205 (36) Two
78 (14) Three
45 (8.0) More than three
$150,000 or more $100,000 -$149,999 $75,000 -$99,999 $50,000 -$74,999 $35,000 -$49,999 $25,000 -$34,999 $15,000 -$24,999 Below $15,000
62 81 105 119 66 70 39 24
Liu S, Chu H. Patient Educ Couns. 2023 Sep;114:1078 42. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% It is likely that my children will get mpox My children are at risk of getting mpox It is possible that my children will get mpox
Strongly disagree Disagree Neither agree nor disagree Agree Strongly Agree Low belief that children were at risk of getting mp ox
Some agreement that vaccination will impact disease
Liu S, Chu H. Patient Educ Couns. 2023 Sep;114:1078 42. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Mpox vaccine will work in preventing disease If my children get the vaccine, they will be less
likely to get mpox
Strongly disagree Disagree Neither agree nor disagree Agree Strongly Agree
•Asked “what is the likelihood that you will”: Likelihood to vaccinate is numerically low, but hig her
than expected
Liu S, Chu H. Patient Educ Couns. 2023 Sep;114:1078 42. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Consider getting an mpox vaccine for your children Try to get an mpox vaccine for your children Actually get your children an mpox vaccine
Very unlikely Unlikely Neutral Likely Very Likely
•Mothers from the survey do not view their children at r isk for mpox.
-However, the intent to vaccinate is higher than exp ected.
•Vaccines were primarily given to adolescents both through public health
and STI clinics.
•Among 21 surveyed ATN providers who provide care for at-risk adolescents:
-Over half already offer the mpox vaccine.
-95% would recommend mpox vaccines for eligible pati ents and do not have
concerns about recommending the vaccine.
-Majority expressed challenges associated with offer ing the vaccine; most
common concern was financial cost to the clinic. Summary of Acceptability data
Is the intervention acceptable to key stakeholders?
No Probably no Uncertain Yes
Varies
Probably Yes
EtR Domain: Health Equity
Vaccine administrations* and cases in adolescents by
race and ethnicity, May 2022 – March 2025
n=92 n=798
*Vaccine administration through September 2024 Case dat a
through March 2025 +Includes 3 mpox cases indicating Multiple races. Mul tiple
races was not reported for vaccine administration da ta.
If Hispanic or Latino was indicated for ethnicity, Race/ethnicity is indicated as Hispanic or Latino; if Hispanic or
Latino ethnicity was not indicated, Race/ethnicity is indicated
as Race Vaccine Administrations Mpox Cases
+
•No groups or settings would be disadvantaged by recomm endation for
JYNNEOS use during mpox outbreaks.
•Immunogenicity is the same for immunocompetent persons 12-17 years.
•Implementation of vaccine should assure equitable access.
•Endorsement by ACIP could facilitate broad acceptance o f recommendation
(e.g., insurance, health departments, pharmacies). Health Equity
What would be the impact on health equity?
Reduced Probably Reduced Probably no impact Increased
Varies
Probably Increased
Don’t know
EtR Domain: Feasibility
•Wide range of vaccinators can administer vaccine (e.g., pediatricians,
pharmacists, public health nurses)
•Wide range of potential facilities: public health, STI clinic, a dolescent health
clinic, pediatrician offices
•Same Immunization Information Systems (IIS) requirement s and reporting
infrastructure as other vaccines
•Limitations to access
-Poor access in rural communities
-Cost of vaccine and 10 vial minimum ordering quanti ty could hinder practices
stocking vaccine
-Pediatricians may defer to STI/adolescent clinics Feasibility Considerations
•Two doses, 28 days apart requires follow up and reminde rs
•JYNNEOS, once thawed/refrigerated, is good for either 4 or 8 weeks,
allowing some time to schedule a second dose.
•Frozen storage is ~18 months Feasibility considerations (cont.)
Is the intervention feasible to implement?
No Probably no Uncertain Yes
Varies
Probably Yes
EtR Domain: Resource Use
•JYNNEOS is commercially available
-Similar mechanisms for billing/reimbursement
•Medicaid/Medicare/317 funding
-Requires similar resources to other vaccine outbrea k responses
•Generally, vaccines are a good use of resources during an outbreak
•Cost-effectiveness of vaccination during a future outbr eak in adolescents is
uncertain Resource Use
Is the intervention a reasonable and efficient allocation of resources?
No Probably no Uncertain Yes
Varies
Probably Yes
Balance of Consequences
Summary of Work Group Interpretation of EtR Domains
Work Group Interpretation EtR Domain
Yes Public Health Problem Benefits and Harms
Large Benefits
Small Harms
Favors intervention Benefit>Harm?
Values
Probably yes Desirable>Undesirable?
Possibly important OR probably no important
uncertainty or variability Uncertainty?
Probably yes Acceptability
Probably increased Equity
Probably yes Feasibility
Probably yes Resource Use
Balance of consequences
There is
insufficient evidence to determine the balance of consequences Desirable consequences clearly
outweigh
undesirable consequences in most settings Desirable consequences
probably
outweigh
undesirable consequences in most settings The balance
between the desirable and undesirable consequences is closely
balanced or
uncertain Undesirable consequences
probably
outweigh
desirable consequences in most settings Undesirable consequences clearly
outweigh
desirable consequences in most settings
•ACIP recommends the 2-dose* JYNNEOS vaccine series fo r persons 12 to 17
years of age at risk of mpox during an mpox outbreak §.
*Dose 2 administered one month after dose 1 §Public health authorities determine whether there i s an mpox outbreak; a
single case may be considered an mpox outbreak at t he discretion of public
health authorities. Other circumstances in which a public health response may
be indicated include ongoing risk of introduction o f mpox into a community
due to disease activity in another geographic area.Proposed Recommendation 1