Document text
National Center for Emerging and Zoonotic Infectious Diseases
Evidence to Recommendations Framework:
Vaccination with JYNNEOS During Mpox Outbreaks
Agam Rao, MD
CAPT, US Public Health Service
Poxvirus and Rabies Branch
Centers for Disease Control and Prevention
Advisory Committee on Immunization Practices
February 22, 2023
Evidence to Recommendations Framework
Evidence to Recommendations (EtR) Framework
Structure to describe information considered in moving from evidence to
ACIP vaccine recommendations
Provide transparency around the impact of additional factors on
deliberations when considering a recommendation
EtR Domains
EtR Domain Question(s)
Public Health Problem • Is the problem of public health importance?
Benefits and Harms • How substantial are the desirable anticipated effects?
• How substantial are the undesirable anticipated effects?
• Do the desirable effects outweigh the undesirable effects?
Values • Does the target population feel the desirable effects are large relative to the undesirable
effects?
• Is there important variability in how patients value the outcome?
Acceptability • Is the intervention acceptable to key stakeholders?
Equity • What would be the impact of the intervention on health equity?
Feasibility • Is the intervention feasible to implement?
Resource Use • Is the intervention a reasonable and efficient allocation of resources?
EtR question
Does ACIP recommend the 2-dose* JYNNEOS vaccine series for persons
aged 18 years and older at risk of mpox during an mpox outbreak?§
*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 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.
EtR Domain: Public Health Problem
Timeline of Notable Human Mpox Events* Multinational
outbreak
Imported human cases to UK and US: 3 Imported Imported
cases to UK cases to UK,
and Israel: 3 Singapore: 2
-First human case identified -Rural settings US outbreak from pet prairie dogs (cohoused with infected small mammals from Ghana): 47 cases
Outbreak in Nigeria involving 17 states: 138 cases
1970 2003 2017 2018 2019 2021 2022
*During 1970-2021, mpox was endemic in 9 African countries: Cameroon, Central African Republic, Cote d’Ivoire,
Democratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone; during recent years, there has been a re-emergence of human cases after decades of no reported cases
U.S. mpox case trends as of February 9, 2023
Many contacts monitored during investigations and
some secondary cases have occurred
United States, July 2021: Traveler returning from Nigeria
– 223 contacts monitored
– No high-risk exposures and no secondary transmissions
– Contacts included flight crew and fellow passengers on international and
domestic flights, friends, Ride-share driver
United Kingdom, 2019 and 2021
– 2019: Healthcare personnel developed mpox
after presumed exposure while changing
bedding of mpox patient
– 2020: Two household contacts of mpox patient developed mpox
Typical manifestations of mpox
Fro m Basgoz N , Brown CM , Smole SC , e t al . Case 24-
2022 : A 31-Year-Old Man with Periana l and Penile Ulcers ,
Recta l Pain , and Rash . Epub ahead of print . Copyrigh t ©
Jun 15 2022 . Massachusetts Medica l Society . Reprinted
with permission fro m Massachusetts Medica l Society
Above : Shared with permission fro m
patients
• Lesions often
perianal and/or
affecting genitals
• Rectal pain
• Abdominal pain
• Rectal bleeding
• Tenesmus
https://www.cdc.gov/mmwr/volumes/71/wr/mm7132e3.htm?s_cid=mm7132e3_w
Severe manifestations: Ocular lesions, neurologic
complications, myopericarditis, and some mucosal lesions
Left: Keratitis
and conjunctival
ulcer
Complications
associated with
some mucosal
lesions
• Painful or Above:
encephalitis obstructing
rectal, urinary Right:
tract, oral and transverse
myelitis genital lesions
and strictures
• Lesions might expose muscle or
bone
Cole J, Choudry S, Kular S,et al. Monkeypox encephalitis with transverse
myelitis in a female patient. Lancet Infect Dis. 2022 Dec 2:S1473-
Rodriguez-Nava G, Kadlecik P, Filardo TD et al. Myocarditis Attributable to Monkeypox Virus
Infection in 2 Patients, United States, 2022. Emerg Infect Dis. 2022 Dec;28(12):2508-2512. 3099(22)00741-1.
Cash Goldwasser S, Labuda SM, McCormick DW et al. (2022 )
Ocular monkeypox, United States—July-September 2022 .
MMWR. 2022 Oct
Above: NSR with TWI in inferior and anterolateral leads of ECG. Patient
with mpox and no underlying medical conditions. Other signs and symptoms: SOB, decreased exercise tolerance, elevated Tn (0.35ng/mL reference <0.07 ng/mL) indicating myocarditis
Severe manifestations from uncontrolled viral spread i n
severely immunocompromised patients
Menezes YR, Miranda AB. Severe disseminated clinical
presentation of monkeypox virus infection in an immunosuppressed patient: first death report in Brazil. Rev Soc Bras Med Trop. 2022 Aug 29;55:e0392. Carrubba S, Geevarghese A, Solli E et al. Novel severe oculocutaneous manifestations of human monkeypox virus infection and their historical analogues. Lancet Infect Dis. 2023 Jan 23:S1473-3099(22)00869-6.
Public health importance
Work group interpretation
Are outbreaks of mpox of public health importance?
EtR Domain: Benefits and Harms
Early Estimates and Population-based, adjusted VE
measures*
Vaccine performance
– Comparison of incidence between vaccinated and unvaccinated persons in 43 U.S.
jurisdictions: Mpox incidence among unvaccinated was 7.4 (95% CI=6.0-9.1) times that
among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier, and 9.6
(95% CI = 6.9–13.2) times that among persons who received dose two ≥ 14 days
earlier
Population-based, adjusted measures of vaccine effectiveness (VE) using electronic
medical records
– Retrospective, population-based cohort study conducted in Israel; 5 mpox infections
among subjects vaccinated with 1 SC dose and 16 among unvaccinated subjects. VE
for dose 1 was 86% (95% CI = 59-95%)
– Nationwide U.S. case-control study with 1:4 ratio of cases matched to controls;
adjusted VE was 35.8% (95% CI: 22.1-47.1%) for one dose and 66.0% (95% CI: 47.7 -
78.1%) for 2 doses, regardless of vaccination route
Early Estimates and Population-based, adjusted
VE measures*
Population-based, adjusted measures of VE using case-control studies
– Case-control study of adult MSM (18-49 years of age) in 12 U.S. jurisdictions;
adjusted VE was 76% (95% CI: 48-89%) for two doses (interim results)
– New York State case-control study of adult male mpox cases matched to STI controls; adjusted VE was 68% (95% CI: 25-86%) for one dose and 89% (95% CI: 44-98%) for two doses (preliminary results)
PEP effectiveness and infections following single dose
France: 10% (11 of 108) of those administered JYNNEOS after mpox
exposure became symptomatic with mpox disease soon after vaccination
(IQR 1-6, median 5 days), although clinical course mild among those
persons
France: Observational study involving people who received single, SC dose; 4% (12 of 276) infected during month after vaccination, none with serious
infection
NYC: Cohort study of individuals with high-risk exposure; VE was 77% with PEP <14 days after last exposure and 79% with PEP <14 days after first exposure
Benefits
Work group interpretation
How substantial are the desirable anticipated effects of mpox
vaccine during an outbreak?
Vaccine Safety: Subcutaneous administration
During May 22, 2022 –January 13, 2023, a total of 1,125,168 JYNNEOS
vaccine doses were administered. CDC monitored JYNNEOS safety using
VAERS and VSD for vaccine recipients of all ages
Adverse events (AEs)
– The most common AEs reported were nonserious and included
injection site reactions, consistent with prelicensure studies
– Reported at similar rates for doses received by intradermal and
subcutaneous administration
– Serious adverse events were rare among adults
Harms
Work group interpretation
How substantial are the undesirable anticipated effects of
mpox vaccine during an outbreak?
Do the desirable effects outweigh the undesirable effects?
Favors intervention Favors comparison Favors both Favors neither Unclear Benefits / Harms
Work group interpretation
What is the balance between the desirable effects relative to
the undesirable effects?
EtR Domain: Values
Vaccination values extrapolated from 2022 outbreak data
Populations at highest risk concerned about mpox
– In August, 53.1% of American Men’s Internet Survey (AMIS) respondents had
concerns about getting mpox
– 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 Aug-Nov, >85% of respondents in the American Transformative HIV Study (AMETHST) were interested in vaccine
– During Aug-Dec, 50% of Porter-Novelli survey responders who identified as LGBTQ+ felt that vaccination is important to protect from mpox
– During Oct-Nov, >70% of MSM in a San Francisco survey of persons experiencing homelessness reported that they would accept or have accepted vaccination
Does the targe t population feel that the desirable effects are large relative to
undesirable effects
No Probably no Uncertain Probably ye s Yes Varies Target population sentiments
Work group interpretation
Does the target population feel that the desirable effects are
large relative to undesirable effects?
Uncertainty or variability in how much people might
value vaccination
During 2022 mpox outbreak, willingness to be vaccinated was dynamic,
and dependent on perceived vulnerabilities
There is clear demand for JYNNEOS vaccination, but many remain unvaccinated for unclear reasons
Demographics of future outbreaks unclear; unknown if values expressed by population most affected by the 2022 mpox outbreak can be extrapolated to all other populations
Possib ly important
uncertainty or
variability Pr obably no
importan t
uncertainty or
variabilit y No impor tant
uncertainty or
variabilit y No kn own
undesirable
outcomes
Target population sentiments
Work group interpretation
Is there important uncertainty about or variability in how much
people value the main outcomes?
Is there important uncertainty about or
outcomes vari ability in how much people value the main
Importan t
uncertaint y
or variabilit y
EtR Domain: Acceptability
Stakeholder perceptions: Sermo survey of clinicians
Sermo*: Online community of >1.3 million
clinicians
July 31 - August 1, 2022 survey results of U.S.
clinicians (n=415): 69% felt U.S. without enough mpox vaccine to handle outbreak
September 12, 2022 survey of U.S. clinicians
(n=62)
• 66% had treated at least one mpox patient
• 76% knew where a patient could get
JYNNEOS vaccination
• 86% wanted to be able to provide vaccination in their office *
https://app.sermo.com/barometer/unitedstates
Stakeholder perceptions: Health departments
Health departments have been requesting JYNNEOS and organizing
vaccination campaigns
https://aspr.hhs.gov/SNS/Pages/JYNNEOS-Distribution.aspx
Vaccine equity pilot program
Enabled jurisdictions to request more than
their allotted amount of JYNNEOS vaccine
Established to
– Support innovative ways to address
vaccination disparities
– Encourage vaccination coordination between health departments and community-based organizations
– Promote innovation to strengthen existing vaccination infrastructure
Acceptability
Work group interpretation
Is the intervention acceptable to key stakeholders
Is the intervention acceptable to key stakeholders
No Probably no Uncertain Probably yes Yes Varies
EtR Domain: Resource Use
Resource Use
JYNNEOS vaccine is provided from HHS’ Strategic National Stockpile (SNS)
free-of-charge
Vaccines are a good use of resources during an outbreak
Costs and challenges associated with mobile, pop-up vaccination sites
Cost-effectiveness analysis of vaccine implementation during the current outbreak planned, but not currently available
Resource Use
Work group interpretation
Is the intervention a reasonable and efficient allocation of
resources
Is the intervention a reasonable and efficient allocation of resources
No Probably no Uncertain Probably yes Yes Varies
EtR Domain: Equity
Equity
No groups or settings disadvantaged by recommendation for JYNNEOS use
during mpox outbreaks
Effectiveness same for all immunocompetent persons
Implementation to assure equitable access will be important particularly among persons who are at high risk for severe outcomes
Might facilitate broad acceptance of the recommendation (e.g., by insurance companies, health departments) because endorsed by ACIP after rigorous review of evidence
Equity
Work group interpretation
What would be the impact on health equity
What would be the impact on health equity?
Reduced Probably Reduced Probably no impact
Increased Varies Don’t know Probably increased
EtR Domain: Feasibility
Feasibility
Feasibility of conducting vaccine campaigns in communities, at events,
and within public health facilities demonstrated in 2022
Can be integrated into providers’ practices
– Standing orders available
– Immunization Information Systems requirements for reporting vaccinations
same as COVID-19 vaccines
– JYNNEOS can be stored refrigerated for 8 weeks
Wide range of vaccinators can administer JYNNEOS
WG discussions
JYNNEOS vaccination probably sustainable during outbreaks
Vaccine access is an important concern
– Increased and convenient access
– Low stigma
Considerations to ensure vaccine equity
– Strong ties with community-based organizations
– Support vaccination events
– Engage trusted messengers
– Ensure access (including in rural areas)
Feasibility
Work group interpretation
Is the intervention feasible to implement?
Is the intervention feasible to implement
No Probably no Uncertain Probably yes Yes Varies
Summary of EtR #1
Domains Domains Domains
Benefits: How
substantial are the desired
anticipated effects Large Values: Does the
target population feel desirable
effects are large Probably
Yes Impact on health equity Probably increase d
Harms: How substantial are undesirable
anticipated
effects? Small Is there important uncertainty about or variability in
values? Possibly
important uncertainty
or
variability Feasible to implement? Yes
Benefit / Harm: Favors intervention Acceptable to stakeholders? Yes Balance of consequences:
Overall certainty of the evidence for the critical
outcomes Moderate Reasonable and
efficient allocation of resources? Varies
Undesirable
consequences probab ly
outweigh desirable
consequences in most
settings
Balance of Consequences
Undesirable
consequences clear ly
outweigh desirable
consequences in mos t
settings Balance between
desirable and undesirable
consequences is close ly
balanced or uncertain
Desirable consequence s
probably outweigh
undesirable consequence s
in mos t setting s X Des irable consequences
clearl y outweig h
undesirable consequence s
in mos t settings There is insufficient evidence
to determine the balance of
consequences
Proposed wording
ACIP recommends the 2-dose* JYNNEOS vaccine series for persons
aged 18 years and older at risk of mpox during an mpox outbreak§
*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 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.
Clinical Considerations
In outbreak setting, vaccine is ideally given pre-exposure but may also be
given as post-exposure prophylaxis (PEP) , although evidence not been
reviewed by ACIP for PEP at this time
Complete 2-dose vaccine series should be given regardless of timing of exposure
Although ACIP has not reviewed the evidence, if there are vaccine supply shortages, ID route of administration can be used
Tentative timeline for ACIP discussions and votes*
Current U S mpox vaccination strateg y remains active : Populations
3Curreantt hUi.Sg. h mripsoxk vsahccoinulatid ocn ostntriatneugy e treo mbaie nsv ian cecfifnecatted
February 2023 June 2023 October 2023
*February 2023 and June 2023 votes do not impact existing recommendations for the current mpox outbreak.
3https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.htmlMpox outbreaks: Use of 2-
dose JYNNEOS for person s
aged ≥ 18 years Mpox outbreaks: Use of 2-dose JYNNEOS
for persons aged <18 year s
-Updates about vaccine effectiveness an d
safetyCo nsider need for longer ter m
vaccination strategy for 2-dose
JYNNEOS
Acknowledgements
Amanda Cohn
Rosalind Carter
Kevin Delaney
Catherine McLean
Faisal Minhaj
Sascha Ellington
Jonathan Duffy
Dani Moulia
Anna Chard
Manisha (Mo) Patel Adam Cohen Saskia Voss
Tom Shimabukuro Dan Payne
Rita Helfand Michael Yeh
Melinda Wharton David Hopkins
Emily Mosites Brett Petersen
Dan Filardo Jane Zucker
Grace Marx Jennifer Rosen
Amy Lansky Eli Rosenberg
Rachel Kachur Sara Oliver
Christine Prue Robbie Goldstein
Questions?
For more information, contact CDC
1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
National Center for Emerging and Zoonotic Infectious Diseases
Division of High-Consequenc e Pathogens and Pathology