National Center for Emerging and Zoonotic Infectious Diseases

Evidence to Recommendations Framework: Vaccination with JYNNEOS During Mpox OutbAdvisory Committee on Immunization PracticesFebruary 22, 2023Agam Rao, MDCAPT, US Public Health ServicePoxvirus and Rabies BranchCenters for Disease Control and Prevention
Evidence to Recommendations Fram
Evidence to Recommendations (EtR) Framew

 Structure to describe information considered in moving from 

ACIP vaccine recommendations

 Provide transparency around the impact of additional factors 

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 

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 paged 18 years and older at risk of mpox during an mpox outbrea

*Dose 2 administered one month after dose 1§ Public health authorities determine whether there is an mpox outbreak; a single case ma

an mpox outbreak at the discretion of public health authorities. Other circumstances in w

health response may be indicated include ongoing risk of introduction of mpox into a comdisease activity in another geographic area.
EtR Domain: Public Health Probl
Timeline of Notable Human Mpox Events*

-First human case identified-Rural settings

1970 2017 2018 2019

Imported cases to UK and Israel: 3

Imported cases to USingapore

Outbreak in Nigeria involving 17 states: 138 cases

US outbreak from pet prairie dogs (cohoused with infected small mammals from Ghana): 47 cases

2003

*During 1970-2021, mpox was endemic in 9 African countries: Cameroon, Central African ReDemocratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone; 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 investigatio

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 internat

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 mpo
Typical manifestations of mpox

From Basgoz N, Brown CM, Smole SC, et al. Case 24-

2022: A 31-Year-Old Man with Perianal and Penile Ulcers, 

Rectal Pain, and Rash. Epub ahead of print. Copyright 

©

Jun 15 2022. Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society

Above: Shared with permission from patients

• Lesions often 

perianal and/or affecting genitals

• Rectal pain• Abdominal pain• Rectal bleeding• Tenesmus

https://www.cdc.gov/mmwr/volumes/71/w
Severe manifestations: Ocular lesions, neurolog

complications, myopericarditis, and some muco

Cash Goldwasser S, Labuda SM, McCormick DW et al. (2022) Ocular monkeypox, United States—July-September 2022. MMWR. 2022 Oct

Left: Keratitis and conjunctival ulcer

Above: encephalitisRight: transverse myelitis

Cole J, Choudry S, Kular myelitis in a female pati3099(22)00741-1. 

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 myocarditisRodriguez-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.

Complications associated with some mucosal lesions• Painful or 

obstructing rectal, urinary tract, oral and genital lesions and strictures

• Lesions might 

expose muscle or bone
Severe manifestations from uncontrolled vira

severely immunocompromised patients

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. 

Menezes YR, Mirapresentation of moimmunosuppresseSoc Bras Med Trop
Public health importance

Work group interpretationAre outbreaks of mpox of public health importance?
EtR Domain: Benefits and Harm
Early Estimates and Population-based, adjuste

measures*

 Vaccine performance

– Comparison of incidence between vaccinated and unvaccinated pers

jurisdictions: Mpox incidence among unvaccinated was 7.4 (95% CI=6

among persons who received only 1 dose of JYNNEOS vaccine ≥14 da(95% CI = 6.9–13.2) times that among persons who received dose twearlier

 Population-based, adjusted measures of vaccine effectiveness (VE) 

medical records

– Retrospective, population-based cohort study conducted in Israel; 5 

among subjects vaccinated with 1 SC dose and 16 among unvaccinatfor dose 1 was 86% (95% CI = 59-95%)

– Nationwide U.S. case-control study with 1:4 ratio of cases matched to 

adjusted VE was 35.8% (95% CI: 22.1-47.1%) for one dose and 66.0% 78.1%) for 2 doses, regardless of vaccination route
Early Estimates and Population-based, adjus

VE measures*

 Population-based, adjusted measures of VE using case-control stud

– Case-control study of adult MSM (18-49 years of age) in 12 U.S

adjusted VE was 76% (95% CI: 48-89%) for two doses (interim r

– New York State case-control study of adult male mpox cases ma

STI controls; adjusted VE was 68% (95% CI: 25-86%) for one do(95% CI: 44-98%) for two doses (preliminary results)
PEP effectiveness and infections following sin

 France: 10% (11 of 108) of those administered JYNNEOS after 

exposure became symptomatic with mpox disease soon after (IQR 1-6, median 5 days), although clinical course mild among persons

 France: Observational study involving people who received sin

4% (12 of 276) infected during month after vaccination, none infection

 NYC: Cohort study of individuals with high-risk exposure; VE w

PEP <14 days after last exposure and 79% with PEP <14 days after first exposure
Benefits

Work group interpretationHow substantial are the desirable anticipated effects of mpoxvaccine during an outbreak?
Vaccine Safety: Subcutaneous administratio

 During May 22, 2022 

– January 13, 2023, a total of 1,125,168 

vaccine doses were administered. CDC monitored JYNNEOS s

VAERS and VSD for vaccine recipients of all ages

 Adverse events (AEs)

– The most common AEs reported were nonserious and inc

injection site reactions, consistent with prelicensure stud

– Reported at similar rates for doses received by intraderm

subcutaneous administration

– Serious adverse events were rare among adults
Harms

Work group interpretationHow substantial are the undesirable anticipated effects of mpox vaccine during an outbreak?
Benefits / Harms

Work group interpretationWhat is the balance between the desirable effects relative to the undesirable effects?

Do the desirable effects outweigh the undesirable effects?

Favors intervention Favors comparison Favors both Favors neit
EtR Domain: Values
Vaccination values extrapolated from 2022 outb

 Populations at highest risk concerned about mpox

– In August, 53.1% of American Men’s Internet Survey (AMIS) res

concerns about getting mpox

– During October-December, an AMIS survey showed that those w

concern had 3.5 times odds of being vaccinated

 Interest in vaccine high

– During Aug-Nov, >85% of respondents in the American Transfor

Study (AMETHST) were interested in vaccine

– During Aug-Dec, 50% of Porter-Novelli survey responders who i

LGBTQ+ felt that vaccination is important to protect from mpox

– During Oct-Nov, >70% of MSM in a San Francisco survey of pers

experiencing homelessness reported that they would accept or vaccination
Target population sentiments

Work group interpretationDoes the target population feel that the desirable effects are large relative to undesirable effects?

Does the target population feel that the desirable effects are large relundesirable effects

No Probably no Uncertain Probably yes Yes Va
Uncertainty or variability in how much peopl

value vaccination During 2022 mpox outbreak, willingness to be vaccinated wa

and dependent on perceived vulnerabilities

 There is clear demand for JYNNEOS vaccination, but many re

unvaccinated for unclear reasons

 Demographics of future outbreaks unclear; unknown if value

population most affected by the 2022 mpox outbreak can be to all other populations
Target population sentiments

Work group interpretationIs there important uncertainty about or variability in how mucpeople value the main outcomes?

Is there important uncertainty about or variability in how much peopoutcomes

Important Possibly important Probably no No importa

uncertainty uncertainty or important uncertainty oor variability variability uncertainty or variability 

variability 
EtR Domain: Acceptability
Stakeholder perceptions: Sermo survey of cl

 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.serm
Stakeholder perceptions: Health departmen

 Health departments have been requesting JYNNEOS and orga

vaccination campaigns

https://aspr.hhs.gov/SNS/Pages/JYN
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 interpretationIs the intervention acceptable to key stakeholders

Is the intervention acceptable to key stakeholders

No Probably no Uncertain Probably yes Yes Va
EtR Domain: Resource Use
Resource Use

 JYNNEOS vaccine is provided from HHS’ Strategic National St

free-of-charge

 Vaccines are a good use of resources during an outbreak Costs and challenges associated with mobile, pop-up vaccina Cost-effectiveness analysis of vaccine implementation during 

outbreak planned, but not currently available 
Resource Use

Work group interpretationIs 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 
EtR Domain: Equity
Equity

 No groups or settings disadvantaged by recommendation for 

during mpox outbreaks

 Effectiveness same for all immunocompetent persons Implementation to assure equitable access will be important 

among persons who are at high risk for severe outcomes

 Might facilitate broad acceptance of the recommendation (e

insurance companies, health departments) because endorserigorous review of evidence
Equity

Work group interpretationWhat would be the impact on health equity

What would be the impact on health equity?

Reduced Probably Reduced Probably no impact Pro

Increased Varies Don’t know
EtR Domain: Feasibility
Feasibility

 Feasibility of conducting vaccine campaigns in communities, 

and within public health facilities demonstrated in 2022

 Can be integrated into providers’ practices – Standing orders available – Immunization Information Systems requirements for reporting 

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 interpretationIs the intervention feasible to implement?

Is the intervention feasible to implement

No Probably no Uncertain Probably yes Yes 
Summary of EtR #1

Domains Domains DomBenefits: How substantial are the desired anticipated effects

Large Values: Does the 

target population feel desirable effects are large

Probably Yes

Impachealth equity

Harms: How substantial are undesirable anticipated effects?

Small Is there important 

uncertainty about or variability in values?

Possibly important uncertainty or variability

Feasibimplem

Benefit / Harm: Favors 

intervention

Acceptable to stakeholders?

Yes Balanc

conseq

Overall certainty of the evidence for the critical outcomes

Moderate Reasonable and 

efficient allocation of resources?

Varies
Balance of Consequences

Undesirable Undesirable Balance 

consequences clearly consequences probably desirable outweigh desirable outweigh desirable consequeconsequences in most consequences in most balanced osettings settingsDesirable consequences Desirable consequences There is in

probably outweigh clearly outweigh to determundesirable consequences undesirable consequences consequein most settings in most settings

X
Proposed wording

ACIP recommends the 2-dose* JYNNEOS vaccine series for persoaged 18 years and older at risk of mpox during an mpox outbrea

*Dose 2 administered one month after dose 1§ Public health authorities determine whether there is an mpox outbreak; a single case ma

an mpox outbreak at the discretion of public health authorities. Other circumstances in w

health response may be indicated include ongoing risk of introduction of mpox into a comdisease activity in another geographic area.
Clinical Considerations

 In outbreak setting, vaccine is ideally given pre-exposure but 

given as post-exposure prophylaxis (PEP) , although evidence reviewed by ACIP for PEP at this time

 Complete 2-dose vaccine series should be given regardless of 

exposure

 Although ACIP has not reviewed the evidence, if there are va

shortages, ID route of administration can be used
Tentative timeline for ACIP discussions and v

Mpox outbreaks: Use of 2-dose JYNNEOS for persons aged ≥ 18 years

February 2023 June 2023 Oc

Mpox outbreaks: Use of 2-dose JYNNEOSfor persons aged <18 years -Updates about vaccine effectiveness and safety

Consider vaccinatJYNNEOS

Current U.S. mpox vaccination strategy remains in effect

Current US mpox vaccination strategy remains active: Popula

at high risk should continue to be vaccinated

§

*February 2023 and June 2023 votes do not impact existing recommendations for the current mpox outbreak. § https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.html
Acknowledgements

 Amanda Cohn Rosalind Carter Kevin Delaney Catherine McLean Faisal Minhaj Sascha Ellington Jonathan Duffy Dani Moulia Anna Chard Manisha (Mo) Patel

 Adam Cohen Tom Shimabukuro Rita Helfand Melinda Wharton Emily Mosites Dan Filardo Grace Marx Amy Lansky Rachel Kachur Christine Prue

          
For more information, contact CDC

1-800-CDC-INFO (232-4636)TTY: 1-888-232-6348 www.cdc.govThe 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 DiseasesDivision of High-Consequence Pathogens and Pathology

Questions?