05 RSV Mat Ped Jones 508

Centers for Disease Control and Prevention
Clinical considerations for RSVpreF maternal vaccine
and nirsevimab
Jefferson Jones MD MPH FAAP
CDR USPHS
Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal
Work Group
Coronavirus and Other Respiratory Viruses Division
National Center for Immunization and Respiratory Diseases
June 22, 2023
2Policy questions for ACIP vote
▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose IM given 24 -
36 weeks gestation) be recommended for pregnant people to prevent RSV disease
in infants?
▪Should one dose of nirsevimab be recommended for infants born during or
entering their first RSV season and <8 months of age at time of immunization?
▪Should one dose of nirsevimab be recommended for children who are at increased
risk of severe RSV disease entering their second RSV season and <20 months of age
at time of immunization?
3Potential advantages of maternal vaccination versus a
monoclonal antibody (mAb)
▪ A maternal vaccine may be lower in price
▪ A mAb is not a traditional vaccine and many issues may complicate implementation
–Insurance coverage, vaccine schedule, immunization registries, safety monitoring
▪ Maternal vaccine provides protection from birth, when infants are at highest risk
–A mAb must be timed correctly to provide protection during the RSV season, and atypical RSV
transmission may lead to unprotected infants
▪ Maternal vaccine induces a polyclonal antibody response, which should be more resilient to
mutations than a monoclonal antibody
–Evidence suggests that mutations resulting in nirsevimab resistance are rare, but naturally
occurring resistant mutations have been detected1,2
–Mutations resulted in poor efficacy of a previous mAb product ( suptavumab )3
1 Abram IDweek 2022. 2 Abram 12th RSV International Symposium 2022. 3Simões CID 2021 .
4Potential advantages of mAb over maternal
vaccination
▪Imbalance for preterm birth observed after RSVpreF vaccine vs. placebo in maternal clinical
trials, but not statistically significant1
▪No head -to-head trials comparing efficacy, but protection from maternal vaccination likely
wanes more quickly1–4
▪Estimated half-lifein nirsevimab trials
–Nirsevimab : 63–73 days5,6
–Infection -induced maternal RSV antibodies: 36 –38 days5
▪Nirsevimab administration can be timed to be given when infant is entering RSV season
1 Kampmann NEJM 2023 . 2 Muller NEJM 2023 . 3Madhi NEJM 2020 . 4Nunes F1000Res 2018 . 5Wilkins Nat Med 2023 . 6Griffin NEJM 2020 .
5Potential advantages of mAb over maternal
vaccination (continued)
▪Protection from maternal vaccination relies on sufficient transplacental transfer of
antibodies, which may be reduced in
–Infants born soon after maternal immunization1
–Infants born premature2
–Maternal disease2
▪Maternal uptake of flu and Tdap vaccines lower than routine childhood vaccines3,4
–Unclear if pregnant people willing to accept multiple vaccines during pregnancy
–However, flu vaccine uptake among children only mildly higher than among pregnant
people
–Uptake of maternal RSVpreF vaccine and nirsevimab unknown
1https://www.cdc.gov/vaccines/pregnancy/vacc -during -after.html. 2Palmerira Clin Dev Immunol 2012 .
3https://www.cdc.gov/flu/fluvaxview/pregnant -women -apr2022.htm. 4Hill MMWR 2023
6Benefits of both products being available
▪Each product has certain advantages
▪Parental preferences may differ, as suggested by survey asking pregnant people
about product preference if both available1
–28% only maternal vaccine
–25% only RSV antibody injection
–38% both
▪Some populations lack access or do not present for prenatal care, precluding
maternal vaccination
▪Scenarios may exist for which use of both products may be warranted to maximize
protection from RSV -associated severe disease–8% none
–1% other
1 Unpublished CDC and University of Iowa/RAND survey of 523 people currently pregnant or pregnant within last 12
months of survey conducted December 21, 2022 -January 2, 2023
7Cost effectiveness summary
▪Cost effectiveness of giving nirsevimab if mother had been vaccinated
–$668,735/QALY if given to all infants
–$486,882/QALY if given to infants born April to September
▪Cost effectiveness of giving RSVpreF to mother if nirsevimab will be
given
–More than $10,000,000/QALY on average
8Challenges if nirsevimab recommendations relate to
maternal vaccination status
▪Maternal vaccination status might be unknown
▪Transferring documentation of maternal vaccination to the healthcare
provider of infant may be difficult
–Limited information available during birth hospitalization
–Less information regarding receipt of prenatal vaccinations may be
available to infant primary care providers
9Draft clinical considerations if both RSVpreF and
nirsevimab are licensed and recommended
▪Either maternal vaccination with RSVpreF or nirsevimab is recommended to
prevent RSV disease, but both products are not needed for most infants
▪Risks and benefits of both RSVpreF and nirsevimab should be considered
when deciding on maternal vaccination
▪If mother vaccinated, nirsevimab can be considered if infant considered to
have insufficient protection from vaccine or is at high risk of severe disease
10Scenarios to consider administration of nirsevimab
when mother has been vaccinated
▪Receipt of maternal vaccine not confirmed by healthcare record
▪Infant born within 14 days of vaccination
▪Infant born premature
▪Healthcare provider recommends maximizing protection because infant at
high risk of severe disease
–Especially important if born >3 months prior to peak of RSV season
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.

Summary: Centers for Disease Control and Prevention Clinical considerations for RSVpreF maternal vaccine  and nirsevimab Jefferson Jones MD MPH FAAP CDR USPHS Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal  Work Group Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases June 22, 2023 2Policy questions for ACIP vote ▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose IM given 24 - 36 weeks gestation) be…


01 mpox Sanchez 508

National Center for Emerging and Zoonotic Infectious Diseases
Mpox Vaccine Work Group
ACIP Meeting
June 23, 2023
Pablo Sanchez MD
The Ohio State University−Nationwide Children’s Hospital
Chair, ACIP Mpox Work Group
Mpox outbreaks
▪Before 2022, rare outside of Africa
▪In Africa, have involved 2 clades:
–Clade I (previously Congo Basin Clade)
–Clade II (previously West African Clade)
▪In United States, have involved Clade II
–Clade IIa:  2003 U.S. outbreak associated with pet prairie dogs
–Clade IIb:  2022/2023 global outbreak associated with male -to-male
sexual contact
▪Historically: Clade I believed to be associated with more severe disease
than Clade II
Severe manifestations observed in severely
immunocompromised persons during the 2022/2023 outbreak:
Clade IIb
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, 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.
ACIP recommendations
▪
▪
▪
–
–With global eradication of smallpox, routine vaccinations against
orthopoxviruses were no longer needed
Routine smallpox vaccinations stopped globally in 1980 (USA, 1972)
ACIP recommendations for persons at occupational risk for orthopoxvirus
infections since 1980
Largest proportion of people recommended to be vaccinated are
research laboratorians who work with orthopoxviruses (including
monkeypox virus [MPXV])
ACAM2000 and JYNNEOS are the vaccines recommended
Current ACIP recommendations for persons at risk for
occupational exposure:  ACAM2000 and JYNNEOS
▪Since 2015, ACAM2000 recommended
▪In November 2021, JYNNEOS recommended as alternative to ACAM2000

ACAM2000 compared to JYNNEOS
Vaccine virus
AdministrationVia multiple percutaneous puncture
technique (single dose)Subcutaneously* via 2 vaccine doses,
28 days apartvirus
TakeInadvertent inoculation and
autoinoculation can occur via vaccine
site lesionNo risk of inadvertent inoculation
and autoinoculation with vaccinia
virus
*During the 2022/2023, intradermal was the preferred route of administration; vaccine effectiveness data
indicates this route has been equally effective
virusACAM2000
Live, replication competent vaccinia Live, replication deficient vaccinia JYNNEOS
Contraindications for ACAM2000 and JYNNEOS

2022/2023 U.S. mpox outbreak:  JYNNEOS
recommended
▪
▪Fewer contraindications and adverse events with JYNNEOS
Before this outbreak, no real -world experience with JYNNEOS
https://www.cdc.gov/poxvirus/mpox/vaccines/index.html
Short-term goal of the Work Group
▪
▪Currently no ACIP recommendation for use of JYNNEOS during mpox
outbreaks
Develop ACIP recommendations for use of JYNNEOS during mpox
outbreaks*
*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.
February 2023 ACIP meeting:  Vote passed for use of
JYNNEOS during outbreaks
ACIP recommends the 2-dose* JYNNEOS vaccine series for persons
aged 18years 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.
Timeline that was proposed during February 2023*
Mpox outbreaks: Use of 2-
dose JYNNEOS for persons
aged ≥ 18 years
February 2023 June 2023 October 2023-Mpox outbreaks: Use of 2-dose JYNNEOS
for persons aged <18 years
-Updates about vaccine effectiveness and
safetyConsider need for longer term
vaccination strategy for 2-dose
JYNNEOS
*These votes do not impact existing recommendations for the current mpox outbreak.
§https://www.cdc.gov/poxvirus/monkeypox/interim -considerations/overview.html
Agenda for today’s meeting
▪Updates about epidemiology, vaccine safety, and vaccine effectiveness
during the ongoing outbreak:  Faisal Minhaj
▪Clinical guidance about the use of 2 -dose JYNNEOS (subcutaneous) series
during mpox outbreaks:  Agam Rao
▪Considerations for long -term protection against mpox :  Discussion in the
context of the ongoing outbreak:  Agam Rao
Tentative timeline for ACIP discussions and votes
ACIP meeting: Clinical
guidance about use of
JYNNEOS during outbrea
June 2023kPublication of MMWR
about use of JYNNEOS
during mpox outbreaks
August/September 2023ACIP meeting: Consider need
for longer term vaccination
strategy for 2-dose JYNNEOS
October 2023 Current US mpox vaccination strategy remains active:  Populations at high
Current U.S. risk mposhox vaculd cinacontiontinue t strategy o be v remains accina in etedffect*
*MMWR publication will not change the clinical guidance posted for the ongoing outbreak:
https://www.cdc.gov/poxvirus/monkeypox/interim -considerations/overview.html
WG members
ACIP Member
Pablo Sánchez
Beth Bell
Ex Officio and Liaison Members
CSTE: Chris Hahn / Paul Cieslak
ASTHO: Ericka McGowan
NACHO: Philip Huang
FDA: Sixun Yang, Clement
Meseda & Alonzo García
ACOG: Howard Minkoff
AAP: Jim CampbellAIM: Rob Schechter / Jane Zucker
APHL:  Jafar Razeq
NIH: Janet Lathey / Kimberly Taylor
IHS: Matthew Clark
NACI: Nicole Forbes / Oliver Baclic
IDSA: Shireesha Dhanireddy / Rajesh Gandhi
Invited Consultants
Subject matter experts: Inger Damon, Stuart
Isaacs, Mike Merchlinsky & Amanda
Zarrabian (HHS/BARDA)
Clinician experts in STIs, HIV, pediatrics,
maternal vaccination, vaccine safety, health
equity, smallpox vaccination strategies,
occupational health
Clinician experts
STIs, HIV, and mpox
(adult and peds):
Jason Zucker
Jeanne Marrazzo
Pablo Tebas
Vince Marconi
Kim Workowski
Bonnie Maldonado
Immunizations (including for special
populations) and vaccine safety:
Ruth Karron
Flor Munoz -Rivas
Kathy EdwardsHealth equity, vaccination strategies
including for smallpox:
Joel Breman
Gerard Vong
Occupational Medicine and worker safety:
Mark Russi
CDC contributors
Mpox epi, lab, and vaccine experts
Brett Petersen
Andrea McCollum
Christy Hutson
Laboratory Response Network:
Julie Villanueva
Infection control, worker safety:
Marie de Perio
David Kuhar
Special populations (e.g., Persons
experiencing homelessness)
Emily MositesVaccine safety
Michael McNeil
Jonathan Duffy
Regulatory Affairs
Yon Yu
STIs and HIV
Laura Bachmann
Leandro Mena
John Brooks
Alexa OsterDrug Services
Julian Jolly
Vaccine
implementation
Liz Velasquez
James Lee
DoD Liaison to CDC
Alan Lam
Work group lead
Agam Rao
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.Thank you!

Summary: National Center for Emerging and Zoonotic Infectious Diseases Mpox Vaccine Work Group ACIP Meeting June 23, 2023 Pablo Sanchez MD The Ohio State University−Nationwide Children’s Hospital Chair, ACIP Mpox Work Group Mpox outbreaks ▪Before 2022, rare outside of Africa ▪In Africa, have involved 2 clades: –Clade I (previously Congo Basin Clade) –Clade II (previously West African Clade) ▪In United States, have involved Clade II –Clade IIa:  2003 U.S. outbreak associated with pet prairie dogs –Clade…


02 mpox Minhaj 508

National Center for Emerging and Zoonotic Infectious Diseases
Updates from the 2022 –2023 U.S. Mpox Outbreak:
Epidemiology, Vaccine Safety, and Vaccine
Effectiveness
ACIP Meeting
June 23, 2023Faisal Syed Minhaj, PharmD, MPH, DABAT
Epidemic Intelligence Service Officer
Poxvirus and Rabies Branch
United States Mpox Case Counts April 2022 –June 2023
https://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html
United States Mpox Case Counts January 1 –June 6, 2023
Uptick in
cases in
Chicago
https://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html
Mpox cases reported to CDC by age and gender May
2022 –June 14, 2023
https://www.cdc.gov/poxvirus/mpox/response/2022/demographics.htmlData were available for 98.9% of cases
reported to CDC
Mpox cases reported to CDC by race and ethnicity May
2022 –June 14, 2023
56      1050    8859   11782  5289   1894     753     340      196       64        71        42        81        10    Count within columns
https://www.cdc.gov/poxvirus/mpox/response/2022/demographics.htmlSubject to reporting
irregularities
Data were available for 93.7%
of cases reported to CDC
Chicago Mpox Cases
Increases in mpox
cases detected
https://www.chicago.gov/city/en/sites/monkeypox/home/data.html
Cluster of cases in Chicago
▪From March 18 –June 12, Chicago identified 40 laboratory confirmed mpox
cases
–All males with a median age of 36 years (IQR 23 –49)
–22 (55%) were vaccinated with 2 doses of JYNNEOS or 1 -dose of ACAM2000
–5 (13%) were partially vaccinated (i.e., 1 dose JYNNEOS)
–13 (33%) were unvaccinated
▪11 were living with HIV
–10 were vaccinated with 2 doses of JYNNEOS or 1 dose of ACAM2000 had
well controlled HIV
▪Median time from 2nddose of JYNNEOS to mpox diagnosis was 8.4 months (IQR
7.9–8.8 months)
https://www.cdc.gov/mmwr/volumes/72/wr/mm7225a6.htm
Cluster of cases in Chicago
▪Individuals with 2 doses of JYNNEOS or 1 dose of ACAM2000 had self -limiting
illness
–Lower prevalence of mucosal lesions
–None were hospitalized
▪Individuals with 2 doses of JYNNEOS or 1 dose of ACAM2000 had a higher
number of sexual partners 3 weeks before symptom onset compared to
partially or unvaccinated
▪Preliminary sequencing indicates the virus is the same B.1 variant of Clade IIB
which is the predominant variant of the 2022 –2023 outbreak
–There were no mutations that would confer increased pathogenicity
▪This investigation is ongoing, however no similar clusters are being seen
elsewhere in the U.S.
https://www.cdc.gov/mmwr/volumes/72/wr/mm7225a6.htm
Epidemiology of Mpox in Less Affected
Populations
Mpox in Pregnant People in the U.S.
▪From May 11, 2022 –May 31, 2023, 27 cases of mpox reported to CDC
occurred in pregnant people
▪All exposure were through close contact with a person with confirmed
infection (including sexual or household contact)
▪Infections occurred in all trimesters of pregnancy
▪11 (40.7%) received tecovirimat without adverse events reported
▪Outcomes
–3 (11.1%) pregnancy losses at <20 weeks
–6 (22.2%) live births
–18 (66.7%) pregnancies ongoing
Neonatal Transmission and Breastfeeding
Considerations
▪Of 6 live births, two neonates developed lesions within one week after
their mothers became symptomatic.
–Both neonates received oral tecovirimat; one received VIGIV.
–Both neonates responded to treatment and were discharged home.
–One breastfeeding neonate developed face and chest lesions 6 days
after the mother developed breast lesions.
▪One woman with isolated ocular lesions continued to breastfeed her 2 -
year -old infant without transmission
–Breastmilk tested on two separate occasions was MPXV PCR negative
VIGIV: vaccinia immune globulin intravenous
Mpox in a U.S. Neonate
▪12 hours after vaginal delivery, it was learned
that dad had active mpox and had contact with
mom prior to delivery
▪Mom developed lesions 1 day after delivery on
the abdomen and tested positive for mpox
▪Baby was given VIGIV as post -exposure
prophylaxis
▪At 4 days old, baby developed scalp lesions and
tested negative for HSV, positive for mpox
▪Baby was given tecovirimat and discharged at 17
days old
▪Full resolution 4 weeks after discharge
Scalp
lesion,
4 days old
Scalp
lesion,
13days
old
Nowalk A, Dunmore E (unpublished) VIGIV: vaccinia immune globulin intravenous
Mpox in a neonate in the United Kingdom
•Nine days before birth, dad developed a
febrile illness, followed by a rash that
resolved prior to the baby’s birth
•Four days after birth, a similar rash
appeared on mom
•Nine days after birth, the infant also
developed a similar rash and diagnosed
with both mpox and adenovirus
•Treated with 14 days of enteral
tecovirimat and intravenous cidofovir
•Critically ill, requiring 4 weeks in ICU and
14 days on mechanical ventilation before
discharged home
Ramnarayan P , Mitting R, N Engl J Med . 2022 Oct 27;387(17):1618 -1620.
Epidemiologic Characteristics of Pediatric Cases in the
U.S., May 17 –September 24, 2022
Characteristic% by age group, yrs
0–4 5–12 13–17
(n = 16) (n = 12) (n = 55)
Sex
Male 75% 50% 89%
Female 25% 50% 11%
Race or ethnicity
Black, non -Hispanic 44% 42% 49%
Hispanic or Latino 31% 42% 34%
White, non -Hispanic 19% 17% 9%
Asian, non -Hispanic — — 4%
American Indian or Alaska Native, non -Hispanic — — 2%
Native Hawaiian or other Pacific Islander, non -Hispanic 6% — —
Other, non -Hispanic — — 2%
Exposure setting and route
Sexual contact — — 97%
Household contact 93% 100% —
Other 7% — 3%
•<1% of U.S. cases among persons <18 years of age
•Among adolescents, cases predominantly after male -to-male sexual
contact
•Among younger children, predominantly household contact
Hennessee I. MMWR Morb Mortal Wkly Rep 2022;71:1407 –1411.
MPXV Infections Among
Children Aged ≤12 Years —
U.S., September 25 –
December 31, 2022
▪Mpox cases in children ≤12
years are rare
▪Transmission to children is
primarily from mpox positive
caregiver interactions
Nemechek K, MMWR Morb Mortal Wkly Rep 2023;72:633 –635.
Healthcare Personnel (HCP) Infections Reported to
CDC
▪During investigation of cases where HCP was noted within a case report
form, the exposure was often outside the workplace
▪After excluding all other more likely exposures, only 23 (0.08%) cases
potentially involved HCP exposed at work
▪HCP infections are very rare
Healthcare Personnel Cases That Consulted CDC (n=6)
▪Three were sharps injuries while trying to aspirate/unroof lesions
–CDC has since revised its recommendations to discourage unroofing
lesions
–Globally, this constitutes the majority of HCP infections
▪Two cases among HCP where improper personal protective equipment was
worn
▪One case where the exposure route was unclear
Vaccine:  Coverage, Safety and Effectiveness
First and Second Doses of JYNNEOS Vaccine
Administrations−United States, May, 2022 to May 2023
Overall vaccine coverage
1-dose: 36.7% and 2-dose: 22.7%
Risk for recurrent mpox outbreak lasting >3 months,
by immunity level —United States, 2023
Pollock ED . MMWR Morb Mortal Wkly Rep 2023;72:568 –573.
Cumulative Monkeypox virus infections relative to
2022, by immunity level —United States, 2023
Pollock ED . MMWR Morb Mortal Wkly Rep 2023;72:568 –573.
Cumulative Monkeypox virus infections relative to
2022, by immunity level —United States, 2023
Pollock ED . MMWR Morb Mortal Wkly Rep 2023;72:568 –573.>50% is needed
to significantly
decrease the risk
of large outbreaks
JYNNEOS Vaccine Safety Monitoring
▪CDC vaccine safety monitoring is ongoing using two surveillance systems:
–Vaccine Adverse Event Reporting System (VAERS)
–Vaccine Safety Datalink (VSD)
▪V-safe data collection for mpox vaccines was available from November
2022 through March 21, 2023
JYNNEOS Vaccine Safety Findings Summary
▪The adverse events most commonly reported to VAERS have been injection
site symptoms (redness, swelling, pain, itching)
▪Uncommon, but expected, adverse events that have been reported to
VAERS include:
–Syncope:        49 reports per million doses administered
–Anaphylaxis:  2 reports per million doses administered
▪Myocarditis and pericarditis are adverse events of special interest
–Observed rates are consistent with expected background rates
JYNNEOS Vaccine Safety Conclusions
▪VAERS and VSD data do not suggest an increased risk for myocarditis or
pericarditis following JYNNEOS, but the possibility of a small risk cannot be
excluded
▪The frequencies of local and systemic reactions reported to v -safe after
mpox vaccine were similar to those reported in clinical trials
▪No new or unexpected safety concerns have been identified
Epic Cosmos Study: Methods
▪Data Source: Epic’s electronic health record (EHR) platform, Cosmos, which includes
records from >173 million patients across the U.S.
▪Design: Case -control analysis, matched 1:4 based on week of index event, HHS region,
and gender identity
–Cases : Patients with anmpox diagnosis or positive orthopoxvirus or MPXV laboratory
result from 8/15 -11/19/2022
–Controls: Patients with an incident HIV diagnosis or HIV pre -exposure prophylaxis
(PrEP ) prescription from 8/15 -11/19/2022
▪Analysis:
–Vaccine effectiveness (VE) estimated using conditional logistic regression
–Adjusted for age, race/ethnicity, social vulnerability index, immunocompromising
conditions
–Stratified by route of administration and immunocompromised status
Epic Cosmos Case -Control Study: VE for 1-Dose and 2-
Dose JYNNEOS vaccination
https://www.nejm.org/doi/full/10.1056/NEJMoa2215201?query=featured_home*Adjusted for age, race/ethnicity, social vulnerability index, and immunocompromising conditions.
Cases/controls matched on week of index event, HHS region, gender identity.
Multi -jurisdictional Case -Control Study: Methods
▪Design: Case -control study
▪Population: Men who have sex with men; ages 18 -49; 12 U.S. jurisdictions
▪Methods:
–Cases identified from jurisdictions’ probable and confirmed mpox case
lists
–Controls identified from healthcare settings providing HIV PrEP or
sexually transmitted infection (STI) clinics
–Demographics, exposure history, and vaccination history collected using
electronic surveys
–Vaccination status confirmed by state immunization registries
–Analysis:
–VE estimated using conditional logistic regression
–Adjusted for age, race/ethnicity, immunocompromising conditions
–Stratified by route of administration and immunocompromised status
Multi -jurisdictional Case -Control Study Results: VE for
1-Dose and 2-Dose JYNNEOS vaccination
https://www.cdc.gov/mmwr/volumes/72/wr/mm7220a3.htm?s_cid=mm7220a3_w

Multi -jurisdictional Case -Control Study Results: VE for
1-Dose and 2-Dose JYNNEOS vaccination
https://www.cdc.gov/mmwr/volumes/72/wr/mm7220a3.htm?s_cid=mm7220a3_w

New York State Case -Control Study: Methods
▪Design: Case -control study
▪Data source: Linkage of case surveillance to immunization registry in New York
State, excluding New York City
▪Population: males at birth aged ≥18 years
▪Methods:
▪Cases : Adult male mpox cases during July 24 –October 31, 2022
▪Controls : Adult male STI cases (rectal gonorrhea or primary syphilis) during July
24 –October 31, 2022
▪Vaccination status obtained from immunization registries
▪Analysis: Conditional logistic regression model adjusted for week of diagnosis,
race, age, region within state
New York State Case -Control Study Results: VE for 1-
Dose and 2-Dose JYNNEOS vaccination
*Adjusted for age, race/ethnicity, week of diagnosis, and geographic region
https://www.cdc.gov/mmwr/volumes/72/wr/mm7220a4.htm

VE against mpox ranges from 36% –75% for 1-Dose and
66% –89% for 2 -Dose JYNNEOS vaccination
Vaccine effectiveness of JYNNEOS against mpox
▪JYNNEOS vaccine is effective at reducing risk of mpox disease
▪Protection provided by both 1 and 2 doses of JYNNEOS vaccine
▪Highest protection provided by 2 doses, regardless of route of
administration
▪Further research needed to evaluate whether immunocompromised status
modulates VE
▪Further research needed to understand the duration of protection
Acknowledgements
▪Sarah Guagliardo
▪Andrea McCollum
▪Agam Rao
▪Omoshalewa Bamkole
▪David Yankey
▪Rosalind Carter
▪Romeo Galang
▪Amanda Cohn
▪Ian Kracalik▪Taina Joseph
▪Anne Kimball
▪Allie Tuttle
▪Marie de Perio
▪David Kuhar
▪Jonathan Duffy
▪Emily Faherty
▪Ian Spicknall
▪Chris Braden▪Varsha Neelam
▪Andrew Nowalk
▪Elizabeth Dunmore
▪Shama Cash -Goldwasser
▪Mukesh Hamal
▪Marisa Hast
▪Rebecca Free
▪Jim Matthias

Summary: National Center for Emerging and Zoonotic Infectious Diseases Updates from the 2022 –2023 U.S. Mpox Outbreak:  Epidemiology, Vaccine Safety, and Vaccine  Effectiveness ACIP Meeting June 23, 2023Faisal Syed Minhaj, PharmD, MPH, DABAT Epidemic Intelligence Service Officer Poxvirus and Rabies Branch United States Mpox Case Counts April 2022 –June 2023 https://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html United States Mpox Case Counts January 1 –June 6, 2023 Uptick in  cases in …


03 mpox Rao 508

National Center for Emerging and Zoonotic Infectious Diseases
Use of JYNNEOS During Mpox Outbreaks:  Clinical
Guidance
Agam Rao, MD
CAPT, US Public Health Service
Medical Officer
Poxvirus and Rabies Branch
Advisory Committee on Immunization Practices
June 23, 2023

  Vote passed during February 2023 ACIP meeting
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.

 Vaccination with JYNNEOS is a 2 -dose series
▪Post -exposure:  Concerning exposure should trigger consideration for
vaccination regardless of where the exposure occurs (e.g., healthcare
setting vs. community)
▪Pre-exposure: Whether specific populations (e.g., children, pregnant
persons) should receive vaccinations is dependent on the risk during a
specific outbreak
▪Goal of clinical guidance:  Provide general information that can inform
decision -making for specific mpox outbreaks

 Clinical guidance
▪Vaccinating at -risk populations during an outbreak
– Persons <18 years of age
– Pregnant persons
– Breastfeeding persons
▪Vaccinating HCP and certain laboratorians during an outbreak
– Healthcare personnel (HCP)
– Certain laboratorians
▪Administration guidance
– Coadministration with COVID -19 vaccines
– Immunoglobulin products
– Other guidance

Vaccinating at -risk populations during an
mpox outbreak

 Mpox in persons <18 years of age, 1970 -2022
▪Central and West Africa, Clades I (n= <1638*) and IIa (n= 6)
–
–
–
–
– 1970 -1985: Increased incidence and severity in children ≤ 8 years of age
compared to adolescents and adults, likely because younger children had not
been routinely vaccinated to prevent smallpox
2006 -2015: No difference in incidence or severity in children compared to
adults, likely reflecting cessation of childhood smallpox vaccinations among
persons who were adults at the time of evaluations
▪United States and United Kingdom, Clades IIa (n= 12) and IIb (n= 125)
2 children hospitalized during 2003 U.S. outbreak and 1 child hospitalized during
2021 in United Kingdom; all recovered
No severe manifestations among U.S. children during current outbreak
Severe manifestation reported among a neonate in UK (adenovirus co -infection)
*Includes 18 –19-year -olds from the Democratic Republic of the Congo

Use of JYNNEOS in persons aged <18 years
▪
▪
▪12-17 years of age, n=349
• No safety signals identified via CDC surveillance  systems
• No efficacy data from pre-licensure trials
• Unable to  evaluate real-world VE during current outbreak
 U.S. JYNNEOS first doses§
administered to pediatric patients by
age and gender

girl
boy
• NIH  clinical trial underway to evaluate safety and efficacy
0-11 years of age, n=377
• No safety signals identified via CDC surveillance  systems
• No efficacy data from pre-licensure trials
• Unable to evaluate real-world VE during current outbreak
• Concerns that dose may be different for those in the
younger ages
• No clinical trials or other studies planned at this time
Data from recent publication* is encouraging § Fewer children  received  2 doses (compared
to 1  dose);  CDC unpublished  data (does not
include data from one state)
* Ladhani et  al. Lancet In  fect  Dis. 20 23

 Clinical guidance for children and adolescents
▪For persons 6 months -17 years, JYNNEOS should be administered as PrEP or PEP
(as indicated by public health authorities for a specific outbreak) if a high -risk
exposure has occurred
–
–
– For younger children (e.g., <6 years of age), clinicians should be aware that no studies involving
JYNNEOS have been performed to determine appropriate dose
Decisions about vaccination with JYNNEOS should involve risk/benefit assessment for every
pediatric age group during a specific outbreak
After completion of ongoing clinical trial, ACIP may consider a vote re: use of JYNNEOS in
children 12 -17 years of age during mpox outbreaks
▪For children < 6 months of age, VIGIV should be administered in lieu of JYNNEOS if
PEP is indicated

 Detection and transmission of MPXV during the
current outbreak
* DNA has been detected at Ct values <35 in recovered patients more than 30 days after illness onset in an upper respiratory tract swab, saliva, and semen.
† The preponderance of existing data support exposure to anorectal and vulvovaginal tissues and fluids as capable of transmit ting infection; however, it is difficult with current evidence to definitively isolate these exposures
from other concomitant exposures (see text).
‡ Includes body modification with piercings and tattooing.
https://www.cdc.gov/poxvirus/monkeypox/about/science -behind -transmission.html

 Mpox in pregnant persons
▪Historically*
–
–
–
– Mpox known to have been transmitted pre and perinatally to at least 2
neonates
Neonatal outcomes among neonates born to mothers who had mpox
(n=5) included a stillbirth, self -limited rash, and healthy neonates
▪During 2022/2023 U.S. outbreak
Outcomes among pregnant women are being evaluated
Transmission to neonate known to have occurred
*This information is limited to published reports
from countries where MPXV is endemic

 Use of JYNNEOS in pregnant persons
▪Unknown if JYNNEOS administered to pregnant persons during 2022/2023
outbreak
▪No adverse events (passively reported via VAERS) have been received
▪2022 ACIP recommendations for persons at risk for occupational exposure
explicitly states JYNNEOS not contraindicated in pregnant persons

 Mpox spread during breastfeeding and use of
JYNNEOS among breastfeeding persons*
▪Mpox known to be transmitted when child exposed to mpox skin lesions
(e.g., under breast)
▪Mpox not known to be transmitted via breast milk; for one patient during
2022 outbreak, breast milk samples negative for MPXV DNA by PCR
▪No information about whether breast -feeding persons received JYNNEOS
during ongoing outbreak; however, no VAERS reports were received that
mentioned breast -feeding persons
*https://www.cdc.gov/mmwr/volumes/72/wr/mm7201a2.htm?s_cid=mm7201a2_w

 Proposed clinical guidance for pregnant and breastfeeding persons
▪JYNNEOS not contraindicated in persons who are pregnant or breastfeeding
▪Available human data insufficient to determine vaccine -associated risks in
pregnancy.  However, animal models including rats and rabbits have shown no
evidence of harm to developing fetus
▪Safety and efficacy of JYNNEOS not been evaluated in breastfeeding women.  It is
not definitively known whether JYNNEOS is excreted in human milk. Data are not
available to assess the impact of JYNNEOS on milk production or the safety of
JYNNEOS in breastfed infants. However, because JYNNEOS vaccine is replication -
deficient, it likely does not present a risk of transmission to breastfed infants and
can be administered to women who are breastfeeding after weighing the benefits
and harms
▪If high -risk exposures cannot be avoided or have already occurred, persons who are
pregnant or breastfeeding may receive JYNNEOS

Vaccinating HCP and certain laboratorians
during an mpox outbreak

  Mpox acquired via laboratory or healthcare exposures
▪2022/2023 U.S. mpox outbreak
– Laboratory personnel: No reports
– HCP: 23 potential exposures
• Most associated with sharps injuries while attempting to unroof, open, or
aspirate mpox lesions*
• Some associated with suboptimal PPE use
▪Historical data from endemic countries
– Laboratory personnel:  No data
– HCP:  Acquired providing care to family members/friends in homes or with
little PPE
*Unroofing or aspirating lesions is discouraged https://www.cdc.gov/poxvirus/mpox/clinicians/prep -
collection -specimens.html

 Detection and transmission of MPXV during the
current outbreak
* DNA has been detected at Ct values <35 in recovered patients more than 30 days after illness onset in an upper respiratory tract swab, saliva, and semen.
† The preponderance of existing data support exposure to anorectal and vulvovaginal tissues and fluids as capable of transmit ting infection; however, it is difficult with current evidence to definitively isolate these exposures
from other concomitant exposures (see text).
‡ Includes body modification with piercings and tattooing.
https://www.cdc.gov/poxvirus/monkeypox/about/science -behind -transmission.html

  Use of JYNNEOS for preexposure vaccination of persons at risk for
occupational exposure to orthopoxviruses :  Recommendations of the
ACIP—United States, 2022
▪For research laboratory personnel* and clinical laboratory personnel
performing diagnostic testing for orthopoxviruses§, ACIP recommends use
of JYNNEOS for primary vaccination as an alternative to ACAM2000
▪For healthcare personnel who administer ACAM2000 or care for patients
infected with orthopoxviruses , ACIP recommends use of JYNNEOS (as an
alternative to ACAM2000) based on shared clinical decision -making
*Research laboratory personnel are those who directly handle cultures or animals contaminated or infected with replication -compe tent vaccinia virus,
recombinant vaccinia viruses derived from replication -competent vaccinia strains (i.e., those that are capable of causing clinic al infection and producing
infectious virus in humans), or other orthopoxviruses that infect humans (e.g., Monkeypox virus, Cowpox virus, and Variola virus)
§Clinical laboratory personnel who perform routine chemistry, hematology, and urinalysis testing, including for patients with suspected or confirmed
orthopoxvirus infections, are not included in this recommendation because their risk for exposure is low

       Pre-exposure prophylaxis:  Use of JYNNEOS during
mpox outbreaks
▪For research laboratory personnel* and clinical laboratory personnel performing
diagnostic testing for mpox§, ACIP recommends use of JYNNEOS for pre-exposure
vaccination as an alternative to ACAM2000
▪For clinical laboratory personnel who handle specimens that may have a higher
possibility of containing replication competent MPXV (e.g., lesion material, throat
swabs, oral swabs, rectal swabs), and certain healthcare personnel who care for
patients infected with mpox or administer ACAM2000 §, ACIP recommends use of
JYNNEOS (as an alternative to ACAM2000) based on shared clinical decision -making
*Research laboratory personnel are those who directly handle cultures or animals contaminated or infected with monkeypox viru s (MPXV)
§Vaccination is not routinely recommended for clinical laboratory personnel who perform routine chemistry, hematology, and urinalysis testing,
including for patients with suspected or confirmed MPXV infection , healthcare personnel who care for patients with mpox or administer ACAM2000.
Recommended infection prevention and control practices are effective in minimizing transmission. Vaccination can be offered b ased on site -and
activity -specific biosafety risk assessments (e.g., identification of laboratory procedures with a high likelihood of generatin g aerosols or inadequate PPE
availability)

 Administration guidance

 Coadministration of JYNNEOS with COVID -19 vaccines
▪There is no required minimum interval between receiving any COVID -19 vaccine
and JYNNEOS vaccine (e.g., for mpox prevention), regardless of which vaccine is
administered first
▪People, particularly adolescent and young adult males, who are recommended to
receive both vaccines might consider waiting 4 weeks between vaccines. This is
because of the observed risk for myocarditis and pericarditis after receipt of
ACAM2000 orthopoxvirus vaccine and COVID -19 vaccines and the hypothetical risk
for myocarditis and pericarditis after JYNNEOS vaccine. However, if a patient’s risk
for mpox or severe disease due to COVID -19 is increased, administration of
JYNNEOS and COVID -19 vaccines should not be delayed

  Implications of JYNNEOS administration in close
temporal proximity to immunoglobulin products
▪Antibodies to measles and varicella high in immune globulin products;
administration of these in close temporal proximity can prevent the
vaccine from entering cells and being effective
▪Antibodies to orthopoxviruses are believed to be low in most immune
globulin products (e.g., IVIG) and will likely remain low in the future
▪Antibodies to orthopoxviruses are present in VIGIV (purified
immunoglobulin from persons vaccinated against smallpox); however,
whether these could prevent the vaccine from being effective is unknown

  Clinical guidance when JYNNEOS and immunoglobulin
products are temporally administered
▪Most immunoglobulin products: No precautions are necessary if JYNNEOS
is administered in close temporal proximity to IVIG
▪VIGIV
– VIGIV could interfere with immune response to JYNNEOS
• Ideally, administration of JYNNEOS should be delayed if VIGIV was recently administered
• The duration for which it should be delayed is unknown; during outbreaks, it is acceptable
to administer a dose of JYNNEOS; however, public health consultation should be obtained
for case specific guidance about an additional dose at a later time
– Unlikely that VIGIV would be administered in close proximity to JYNNEOS

 Other administration guidance
▪Unintentional delays do not require restarting the series; the second dose
should be administered as soon as possible even if >1 year has elapsed
▪In settings where subcutaneous administration is not preferred (e.g.,
vaccine is in short supply), the vaccine can be administered intradermally
▪In settings where intradermal administration is not possible (e.g., because
staff are not trained or uncomfortable)
– Jurisdictions may administer subcutaneous vaccinations and prioritize first doses of the 2 -dose
JYNNEOS series
– Second doses should be administered as soon as vaccine availability allows
▪Decisions about vaccine administration should ensure equitable
distribution of vaccine doses

 Acknowledgements
▪Faisal Minhaj ▪Amanda Cohn
▪Jim Campbell ▪Melinda Wharton
▪Jafar Razeq ▪Manisha (Mo) Patel
▪Mark Russi ▪Paul Rota
▪Howard Minkoff ▪Rosalind Carter
▪Sathesh Panayampalli ▪Catherine McLean
▪Christina Hutson ▪Jonathan Duffy
▪David Kuhar ▪Ian Kracalik
▪Marie de Perio ▪Leora Feldstein
▪John Brooks ▪Andrea McCollum ▪ACIP Mpox WG
▪Sara Oliver
▪Tara Anderson
▪Evelyn Twentyman
▪Allie Tuttle
▪AAP’s COID and
Redbook

   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 -Consequence Pathogens and Pathology

Summary: National Center for Emerging and Zoonotic Infectious Diseases  Use of JYNNEOS During Mpox Outbreaks:  Clinical  Guidance  Agam Rao, MD  CAPT, US Public Health Service  Medical Officer  Poxvirus and Rabies Branch  Advisory Committee on Immunization Practices  June 23, 2023                      Vote passed during February 2023 ACIP meeting  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…


04 mpox Rao 508

National Center for Emerging and Zoonotic Infectious Diseases
Considerations for long -term protection against mpox
Advisory Committee on Immunization Practices
June 23, 2023Agam Rao, MD
CAPT, US Public Health Service
Medical Officer
Poxvirus and Rabies Branch
CDC collaborative studies examining serologic
response to JYNNEOS vaccinations
Study Goals Timepoints/Duration Participant Information
•DRC
•Healthcare personnel
•Democratic Republic of the
Congo, Tshuapa Province•Safety
•Immunogenicity
•Effectiveness•2-year studies
•Serum obtained on days 0,
14, 28, and 42, and 6, 12,
18, 24 months
•Booster: 5 years
•Serum obtained on days 0,
7, 14•1000 participants SC/SC liquid
formulation
•600 participants SC/SC lyophilized
formulation
•~170 participants (Booster)
•DC PEP++
•Expanded post -exposure
prophylaxis in MSM with
behaviors that increase risk
for mpox
•DC Health
•Washington, DC•Immunogenicity
•Comparison between
different routes of
vaccination•2-year study
•Days 0, 28, and 42 -56 and 6
months
•12, 18, and 24 months
planned. •330 participants
•Participants with 2 timepoints (n=216),
3 timepoints (n=70), or all 4 timepoints
(n=66)
CDC studies examining serologic response to JYNNEOS
vaccinations
Study Goals Timepoints/Duration Participant Information
•DRC
•Healthcare personnel
Democratic Republic of the
Congo, Tshuapa Province•Safety
•Immunogenicity
•Effectiveness•2-year studies
•Serum obtained on days 0,
14, 28, and 42, and 6, 12,
18, 24 months
•Booster dose: 5 years
•Serum obtained on days 0,
7, 14•1000 participants SC/SC liquid
formulation
•600 participants SC/SC lyophilized
formulation
•~170 participants (Booster)
•DC PEP++
•Expanded post -exposure
prophylaxis in MSM with
behaviors that increase risk
for mpox
•DC Health
•Washington, DC•Immunogenicity
•Comparison between
different routes of
vaccination•2-year study
•Days 0, 28, and 42 -56 and 6
months
•12, 18, and 24 months
planned. •330 participants
•Participants with 2 timepoints (n=216),
3 timepoints (n=70), or all 4 timepoints
(n=66)

CDC studies examining serologic response to JYNNEOS
vaccinations
Study Goals Timepoints/Duration Participant Information
•DRC
•Healthcare personnel
Democratic Republic of the
Congo, Tshuapa Province•Safety
•Immunogenicity
•Effectiveness•2-year studies
•Serum obtained on days 0,
14, 28, and 42, and 6, 12,
18, 24 months
•Booster dose: 5 years
•Serum obtained on days 0,
7, 14•1000 participants SC/SC liquid
formulation
•600 participants SC/SC lyophilized
formulation
•~170 participants (Booster)
•DC PEP++
•Expanded post -exposure
prophylaxis in MSM with
behaviors that increase risk
for mpox
•DC Health
•Washington, DC•Immunogenicity
•Comparison between
different routes of
vaccination•2-year study
•Days 0, 28, and 42 -56 and 6
months
•12, 18, and 24 months
planned. •330 participants
•Participants with 2 timepoints (n=216),
3 timepoints (n=70), or all 4 timepoints
(n=66)
CDC studies examining serologic response to JYNNEOS
vaccinations
Study Goals Timepoints/Duration Participant Information
•DRC
•Healthcare personnel
Democratic Republic of the
Congo, Tshuapa Province•Safety
•Immunogenicity
•Effectiveness•2-year studies
•Serum obtained on days 0,
14, 28, and 42, and 6, 12,
18, 24 months
•Booster dose: 5 years
•Serum obtained on days 0,
7, 14•1000 participants SC/SC liquid
formulation
•600 participants SC/SC lyophilized
formulation
•~170 participants (Booster)
•DC PEP++
•Expanded post -exposure
prophylaxis in MSM with
behaviors that increase risk
for mpox
•DC Health
•Washington, DC•Immunogenicity
•Comparison between
different routes of
vaccination•2-year study
•Days 0, 28, and 42 -56 and 6
months
•12, 18, and 24 months
planned. •330 participants
•Participants with 2 timepoints (n=216),
3 timepoints (n=70), or all 4 timepoints
(n=66)
DRC study:  Detection of IgG antibody after JYNNEOS
vaccination
▪ Serum specimens tested for
presence of orthopoxvirus -specific
IgG antibody using an enzyme -
linked immunosorbent assay (ELISA)
▪ Positivity determined by Optical
Density (OD) –cutoff value (COV)
▪ Circulating IgG levels peaked slower
and lower in persons who received
no previous orthopoxvirus vaccine
▪ Circulating IgG levels stayed higher
for a longer period of time in
persons previously vaccinated
No previous orthopoxvirus
vaccinationPrior Vaccination*
Days from JYNNEOS dose 1

2022 ACIP recommendations for persons at
occupational risk for orthopoxvirus exposures
▪Reviewed data indicated an anamnestic response occurs 2 years after the
2-dose series
▪ACIP recommendations:  persons (typically laboratorians) at occupational
risk for variola virus and MPXV exposures should receive JYNNEOS booster
doses every 2 years
▪No data to indicate whether anamnestic response would occur >2 years
after 2 -dose series; standard -of-care for these persons working with
research grade virus has been booster doses
WG’s interpretation
•Significance of waning circulating antibody levels is unknown
•Anamnestic response elicited 2 years after JYNNEOS primary series
•2022 ACIP recommendations were for exposures that are different from
those experienced during the current outbreak
Real -world data during 2022/2023 U.S. mpox outbreak
▪VE studies
–3 studies: NY State, Epic Cosmos, and Multijurisdictional Case -Control Studies
–VE ranged from 36% –75% for 1 dose and 66% –89% for 2 doses
▪Mpox cases among persons who received 2 doses have occurred:  Some
cases expected; reported as early as August 2022
▪2023 Chicago cluster involving persons who received 2 JYNNEOS doses*
–No U.S. clusters of a similar size reported
–No hospitalizations; opiates not typically prescribed for pain control
–Sequences typical of B.1 variant of MPXV Clade IIb; no mutations that would
confer increased pathogenicity
*For most, at least one dose (and often both doses) were administered
subcutaneously
WG’s interpretation
Third dose currently not indicated for entire population eligible for vaccination
Additional vaccine doses for
immunocompromised persons, including
persons with HIV
Safety of third dose of JYNNEOS
Minhaj et al, unpublished data, 2023020406080100
Any Reaction Pain Edema Pruritis Induration Erythema Tenderness OtherPercentDose 1 Dose 2 Dose 3Select vaccine -associated adverse events, by dose, healthcare personnel in
Democratic Republic of Congo (n=706 for first and second doses and n=170 for 3rd
dose)Limitation
▪Study population may not be
representative of U.S. populationCurrent Knowledge
CDC’s DRC study: Study of HCP shows
increased adverse events among
recipients of 3rddose at 5 years after
primary series
Safety of third dose of JYNNEOS in persons with HIV
Overton 2020 VaccineLimitation
Small numbers of total subjects;
only 30 patients received third
dose; difficult to know likelihood of
increased adverse eventsCurrent Knowledge
Study of persons with HIV (CD4 100 –
500) shows increased adverse events
(albeit not significant) among
recipients of third dose at week 12
020406080100
Any AE Grade 3 AE Site Pain Pruritis Induration Myalgia FatiguePercent2 doses, standard volume 2 doses, double volume 3 doses, standard volumeSelect vaccine -associated adverse events, by dose, among persons with HIV in the United States (n=87 for 1stand
2nddoses, n= 30 for third dose)
WG’s interpretation
Third dose might result in more adverse events; this could deter some persons
from receiving first and second doses
Serologic Response to JYNNEOS among persons with HIV
Current Knowledge
▪For nearly 600 persons with CD4
>200*, serologic response to 2 -dose
series equivalent to response in
persons without HIV
* measured in cells/mm3Limitation
▪No assessment of serologic
response for persons with CD4
<100
Greenberg 2013 J Infect Dis ; Overton 2015 Open Forum Infect Dis ;

Serologic Response to JYNNEOS among persons with HIV
Current Knowledge
▪For persons with CD4 100 -500*
and lifetime nadir <200*, serologic
response of 3 doses is similar to 2
doses
▪Review of unpublished data:  No
correlation between low CD4 count
and antibodies after vaccine
* measured in cells/mm3Limitation
▪Serologic correlate of protective
immunity unknown
▪Small number of subjects: only
26 subjects in 3 -dose arm
Overton 2020 Vaccine

Cases Controls Adjusted †VE (95% CI)
Partial vaccination VE,
immunocompromised22 52 51.0% ( -27.6 –81.2)
Full vaccination VE,
immunocompromised9 31 70.2% ( -37.9 –93.6)VE of JYNNEOS in persons with self -reported
immunocompromise (including HIV)
Current Knowledge
VE point estimates for persons who are
immunocompromised* lower than for
general population of vaccinated
persons for both 1 and 2 dosesLimitation
▪Estimates do not differ statistically
from estimates for general
population
▪Few persons for whom this was
evaluated; Confidence Intervals wide
https://www. cdc.gov/mmwr/volumes/72/wr/mm7220a3.htm?s_cid=mm7220a3_w* predominately HIV (CD4 cell count not specified)
Vaccine Effectiveness (%)
†Adjusted for age, race/ethnicity, immunocompromised status, reported close contact with a
confirmed/suspected mpox case in 3 weeks prior to index event, and month of index event
Severity of infections among fully vaccinated: National
reporting and anecdotal reports
Limitation
▪Data e xtrapolated from surveillance
and consultation data ; no formal
review of electronic health records
linked to vaccine registries
▪Not known whether persons who do
not respond to 2 doses of JYNNEOS
would respond to a third doseCurrent Knowledge
▪>10,000 mpox cases among persons with
HIV; however n o confirmed reports of
severe mpox illness after full vaccination
▪CDC reviewed data reported from health
departments for fully vaccinated persons
with mpox and confirmed none were
hospitalized due to severe manifestations
of mpox
▪Anecdotally, CDC told there was a severe
case in a patient who was not fully
vaccinated; however, details not known
WG’s interpretation
There is no convincing data to indicate patients with moderate -severe
immunocompromise would benefit from an additional dose of JYNNEOS
First and Second Doses of JYNNEOS Vaccine
Administrations−United States, May, 2022 to May 2023
Overall vaccine coverage
1-dose: 36.7% and 2-dose: 22.7%
Conclusions
▪WG prefers no CDC recommendation for third JYNNEOS dose at this time,
including for persons with advanced HIV or other severe
immunocompromise
▪WG emphasized several strategies
–Encourage 2 -dose vaccinations among persons who do not have immunity*
–Prevent or minimize life -threatening manifestations
•Optimizing immune function (e.g., with HIV antiretrovirals), ideally before mpox exposure
•Using CDC interim treatment considerations§to manage patients with (or at risk of)
severe manifestations of mpox
*e.g., persons who have not had mpox
§Rao et al. 2023. MMWR
Next steps
▪Continue to collect and evaluate any existing data, particularly about use of
JYNNEOS in immunocompromised persons
▪Attempt to characterize severity of mpox cases experienced by people who
received 2 JYNNEOS doses
▪Continue ongoing VE studies
▪Update CDC interim clinical considerations* if additional JYNNEOS vaccine
doses are recommended
Acknowledgements
▪ACIP mpox WG
▪John Brooks
▪Rosalind Carter
▪Chris Braden
▪Christy Hutson
▪Sathesh Panayampalli
▪Michael Townsend
▪Shireesha Dhanireddy
▪Inger Damon
▪Faisal Minhaj▪Erin Whitehouse
▪Allie Tuttle
▪Sarah Guagliardo
▪William Bower
▪Andrea McCollum
▪Emily Faherty
▪Willie Bower
▪Christy Hughes
▪Bavarian Nordic
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 -Consequence Pathogens and PathologyQuestions and Comments?

Summary: National Center for Emerging and Zoonotic Infectious Diseases Considerations for long -term protection against mpox Advisory Committee on Immunization Practices June 23, 2023Agam Rao, MD CAPT, US Public Health Service Medical Officer Poxvirus and Rabies Branch CDC collaborative studies examining serologic  response to JYNNEOS vaccinations Study Goals Timepoints/Duration Participant Information •DRC •Healthcare personnel •Democratic Republic of the  Congo, Tshuapa Province•Safety…


01 Mening Poehling 508

National Center for Immunization & Respiratory Diseases
ACIP Meningococcal Vaccines Work Group
Introduction
Katherine Poehling, MD, MPH
Work Group Chair
June 23, 2023

2Meningococcal Vaccines Work Group
▪ ACIP Members on the WG
–Kathy Poehling (Chair)
–Lynn Bahta
–Jamie Loehr
▪ Ex Officio WG Members
–Margaret Bash (FDA)
–Mark Connelly (FDA)
–Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
–Amra Resic (AAFP)
–Samir Shah (AAP)
–Sharon McMullen (ACHA)
–Cacky Tate (AIM)
–Paul Cieslak (CSTE)
–Kathy Hsu (IDSA)
–Joseline Zafack (NACI)
–Jeff Goad (NFID)
–Jessica Cataldi (PIDS)
–Amy Middleman (SAHM)
–David Stephens (Emory)▪ CDC Contributors
–Jenn Collins (DBD/NCIRD)
–Lucy McNamara (DBD/NCIRD)
–LeAnne Fox (DBD/NCIRD)
–Susan Hariri (DBD/NCIRD)
–Amy Rubis (DBD/NCIRD)
–Noele Nelson (DBD/NCIRD)
–Alison Albert (DBD/NCIRD)
–Angela Jiles (DBD/NCIRD)
–Jonathan Duffy (DHQP/NCEZID)
–Tanya Myers (DHQP/NCEZID)
–Ismael Ortega -Sanchez (DVD/NCIRD)
–Liz Velazquez (ISD/NCIRD)
–Jessica MacNeil (ACIP Secretariat)
▪ GRADE/EtR Support
–Doug Campos -Outcalt (Arizona)
–Rebecca Morgan (Case Western Reserve)
3February ACIP Meeting Recap
▪
▪
▪Epidemiology of meningococcal disease in the United States
Pfizer’s MenABCWY vaccine clinical trials data
Work Group interpretation of Pfizer’s MenABCWY trials data
4Summary of Recent Work Group Activities Involving Pfizer Vaccine
▪
▪Pfizer and CDC staff presented their cost effectiveness models for Pfizer’s
pentavalent vaccine
Work group members reviewed GRADE and EtR findings for Pfizer’s vaccine
and deliberated about what to propose to ACIP
5Agenda for Today
▪
–
▪
–CDC’s cost effectiveness model
Dr. Ismael Ortega -Sanchez, CDC
Work group’s GRADE/EtR assessment results
Dr. Sam Crowe, CDC

Summary: National Center for Immunization & Respiratory Diseases ACIP Meningococcal Vaccines Work Group  Introduction Katherine Poehling, MD, MPH Work Group Chair June 23, 2023  2Meningococcal Vaccines Work Group ▪ ACIP Members on the WG –Kathy Poehling (Chair) –Lynn Bahta –Jamie Loehr ▪ Ex Officio WG Members –Margaret Bash (FDA) –Mark Connelly (FDA) –Francisco Leyva (NIH) ▪ WG Liaisons and Consultants –Amra Resic (AAFP) –Samir Shah (AAP)  –Sharon McMullen (ACHA) –Cacky Tate (AIM) –Paul Cieslak (CSTE)…


02 Mening Ortega Sanchez 508

The Cost -effectiveness of a Potential Pentavalent
Meningococcal Conjugate Vaccine (Men ABCWY)
versus the Current Men ACWY and Men B
vaccines for US Adolescents
Ismael R. Ortega -Sanchez, PhD
CDC/NCIRD
ACIP meeting, June 23, 2023
Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily
represent the views of the Centers for Disease Control and Prevention. 1

2Conflict of Interest
CDC/NCIRD collaborators:  All collaborators, No conflict of interest
•Ismael R Ortega -Sanchez
•Samuel James Crowe
•Lucy Alexandra McNamara
Acknowledgements
•Members of the Meningococcal ACIP working group
•Also, for review and comments provided by the economic team at ISD/NCIRD

Overview
•Policy question: Should the pentavalent vaccine (Men ABCWY) be
considered as an option for Men ACWY/Men B vaccination in people
currently recommended to receive both vaccines?
3Current vaccination Potential vaccination strategies
First dose Second dose First dose Second dose Third dose Key Label
At 11 -12 yrsold
with MenACWYAt 16 yrsold
with MenACWYAt 11 -12 yrsold with
MenACWYAt 16 yrsold with
MenABCWYAt 16 yrsold with
MenBQ-P-B
At 11 -12 yrsold with
MenABCWYAt 16 yrsold with
MenABCWYNone (N) P-P-N
At 16 yrs old
with Men BAt 16 yrsold
with Men BAt 11 -12 yrsold with
MenACWYAt 16 yrsold with
MenABCWYAt 16 yrsold with
MenABCWYQ-P-P
At 11 -12 yrsold with
MenABCWYAt 16 yrsold with
MenABCWYAt 16 yrsold with
MenABCWYP-P-P
Men ABCWY = Potential pentavalent vaccine (P) with serogroups A, B, C W Y
Men ACWY = currently recommended quadrivalent vaccine ( Q) for serogroups A, C, W, Y,
Men B =currently recommended monovalent vaccine for serogroup B
Economic analysis
Question : Is vaccinating adolescents 11 -16 years old with Pentavalent vaccine
series to prevent Invasive Meningococcal Disease in adolescents cost-effective ?
Comparator Interventions
Base -case scenario: What is the Incremental cost -effectiveness of vaccinating
healthy adolescents 11 -12 and 16 years old with Pentavalent vaccine relative to
using Men ACWY and Men B vaccines ?
4MenACWY vaccine: one
dose at 11 -12 years and
one dose at 16 years.
(Q-Q)
MenB vaccines: two
doses at 16 years.
(B-B)Use of Pentavalent
MenABCWY vaccine
combined e ither as
Q-P-B
P-P-N
Q-P-P
or P-P-P
Methods: Study question
Objectives :
•Toanalyze theimpact ofeach meningococcal vaccination strategy fortheprevention ofInvasive
Meningococcal Disease -related medical care, long-term sequalae and deaths among US
adolescents .
•Tocompare thehealth and cost impact associated with theuse ofpentavalent meningococcal
vaccine vs.current quadrivalent Men ACWY andMen Bmeningococcal vaccines, toestimate cost-
effectiveness interms ofhealth -related quality oflife,based oncurrently available data.
Perspective
•Base case ispresented from asocietal perspective, including
•Quality -of-lifeimpact tocases andindirect costs intheform ofproductivity lossandlifetime lost
earnings duetoaIMD-related acute disease, long-term sequelae ordeath .
5
Methods: Time frame and analytic horizon
Time frame and analytic horizon:
•Intervention time frame: cohort of 11yrs followed until 25yrs of age
•Meningococcal serogroup specific cases annually for 15 years
•Long term sequelae and death for 15 years
•Analytic horizon:
•Outcomes counted annually or cumulative for 15 year
•IMD disease long -term sequelae complications counted annually or cumulative for 15 years
•Lifetime medical and indirect cost of disabilities and deaths
Discounting:
•3% annual discount rate applied to cost and health outcomes .
6
Methods: the model
Static decision analytic model
•Able to track 11 -year-olds cohort yearly
with states that transition from
susceptibility, infected IMD, recovered
or death
•Monte Carlo simulations for uncertainty
and probabilistic sensitivity analyses
•Allowing pairwise incremental
comparison of hypothetical strategies
versus the standard of care
•Aggregating the associated IMD health
outcomes and costs
•With specific vaccination program
effectiveness, safety and costs
•For a cohort of 11 -year-olds followed for
15 years 7
recoveredvaccinated
Invasive Meningococcal
DiseaseNon-invasive
Disease
8Prevention of:
•IMD cases
•Associated sequelae
•Associated deaths
QALYs saved
$/Life year saved
$/QALY saved
NNV avert a:
•IMD case
•Complication
•DeathEpidemiologic
Data
Vaccine
Characteristics
Acute and
Long -term
Cost Data
Indirect
Cost
DataQuality
Of
Life
DataOther
Parameters
Cohort
ModelMethods: Inputs and main outcomes
9Epidemiologic Data
•Age-year -and B+C+Y+W serogroup -specific pre -vaccine and vaccine era
incidence rates
•1996 -2005 (pre -vaccine) and 2006 -2020 (“vaccine era” for serogroups CWY)
•1994 -2013 (pre -vaccine) and 2017 -2020 (“vaccine era” for serogroup B)
•Age-and serogroup -specific case fatality ratios
•Proportion of survivors with sequelae by condition
10Changes in the Average Annual Incidence in Vaccine Serogroups
BCYW by Age per 100,000
Source: Data from ABC Core Surveillance and NNDSS
Note: Trend and variability across years are used for range of uncertainties and sensitivity analyses •Rates of IMD disease
remain relatively
higher in late
adolescence, but in
general rates have
been declining for all
age groups.
•Overall, IMD
incidence rates are
one sixth of those
from recent pre -
vaccine era
0.000.200.400.600.801.001.201.401.60
=<10 11 12 13 14 15 16 17 18 19 20 21 22 >=23IMD incidence per 100,000
AgeCWY & B PreVaxs
CWY & B  VaxsEra
11Background mortality and IMD Case Fatality Ratios by Age Group and
Serogroups CYW ,  Serogroup B and Serogroups BCWY *
*CFR data is from NNDSS for 2008 -202000.050.10.150.20.25
0-4m 5-11m 1yr 2- 4yrs 5-10yrs 11-17yrs 18-22yrs 23-32yrs 33-64yrs >=65yrsCase fatality rate of IMD
Age group B
C Y W
B C Y WAge (years) US mortality rates
(per 100,000)
11 12.5
12 14.8
13 18.6
14 24.2
15 32.2
16 43.0
17 56.4
18 71.7
19 84.4
20 94.1
21 102.7
22 109.1
23 114.8
24 119.9
25 125.3
26 131.1
All other causes, all races, both sexes from 2020
Lifetables, Social Security Agency
https://www.ssa.gov/oact/STATS/table4c6.html
12Percent of Survivor Cases with Sequelae by Type of
Condition
*Shepard et al. Pediatrics. 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/
Ortega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/
**Edwards et al . J Pediatrics 1981; 99:540 -5   https://pubmed.ncbi.nlm.nih.gov/7277093/
*** Baraff et al . PIDJ 1993;12:389 -94 https://pubmed.ncbi.nlm.nih.gov/8327300/Skin scarring 7.6        (0 -19) Included*
Single amputation 1.9     (0.5 -10) Included*
Multiple amputations 1.2     (0.02 -6) Included*
Hearing loss** 8.8        (2 -20) Included*
Significant long term neurologic
disability***2.1   (0.02 -11) Included*
Initial vaccine effectiveness by vaccine and
serogroup
13QUADRIVALENT MEN B PENTAVALENT
Base -case Low High Base -case Low High Base -case Low High
First DOSE Men ACWY 93% 73% 98% 94% 62% 96%
2nd + DOSE Men ACWY 97% 73% 98% 97% 94% 99%
First DOSE Men B 60% -- -- 60%
2nd + DOSE Men B 85% 50% 99% 88% 79% 99%
Values and assumptions on initial protection are based on various sources:
Phase 3 noninferiority initial vaccine efficacy by single dose (at 11 -12yrs) and second -dose (16yrs) of pentavalent (Men ABCWY) vaccine as reported by Pfizer (data on
file).
Cohn AC, MacNeil JR, Harrison LH, et al. Active Bacterial Core Surveillance (ABCs) Team and MeningNet Surveillance Partners. Effectiveness and Duration of Protection
of One Dose of a Meningococcal Conjugate Vaccine. Pediatrics. 2017 Feb;139(2):e20162193. doi: 10.1542/peds.2016 -2193. PMID: 28100689; PMCID: PMC8353579.
0%20%40%60%80%100%120%
0 1 2 3 4 5 6 7 8Residual protection
Years after fully vaccinatedAssumption: Residual protection by vaccine
and serogroup
14Men ACWY Men B
Assumptions on residual protection are based on various sources:
•Sero -protection is assumed to persist 4 -5 years for a single dose of Men ACWY and Men ABCWY (based on hSBA sero bactericidal assay from Pfizer’s clinical trials report)
•Duration of protection ( DoP) for pentavalent Men ABCWY vaccines is assumed to follow Men ACWY
•Duration of protection ( DoP) for Men B is after fully immunized with 2 doses
•The pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available surveillance or Phase 3 dat a
•Cohn AC, MacNeil JR, Harrison LH, et al. Active Bacterial Core Surveillance (ABCs) Team and MeningNet Surveillance Partners. Effectiveness and Duration of Protection of One
Dose of a Meningococcal Conjugate Vaccine. Pediatrics. 2017 Feb;139(2):e20162193. doi: 10.1542/peds.2016 -2193. PMID: 28100689; PMCID: PMC8353579.0%20%40%60%80%100%120%
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15Residual Protection
Years after vaccination with first doseDoP 1st Dose Mean DoP 2nd Dose Mean
15Cost of vaccination per vaccine type, cost per
dose* and vaccine administration setting
* 2023 public and private sector cost per dose; VFC Current CDC Vaccine Price List, CDC. Although not included in these costs , rates and costs
of moderate and severe adverse event were taken from the UK experience with MCC
Trotter et al., BMJ 2002; Ortega -Sanchez et al., CID2008.  They were applied to all vaccines
**Proportions of vaccine purchased at public and private sector and procurement from either private or private providers were based on
difference sources (i.e., Glazner et al., Pediatrics 2009)
*** Calculated using a hypothetical range of prices as released by Pfizer Inc. for Men ABCWY.Quadrivalent (Q) Men B (B) Pentavalent (P)
public sector cost for vaccine $105.6 $141.84 $230.0
public sector admin cost $15.0 $15.0 $15.0
private sector cost for vaccine $156.0 $211.32 $250.0
private sector admin cost $30.0 $30.0 $30.0
% vaccine purchased at public sector price 53.75% 53.75% 53.75%
% vaccine purchased at private sector price 46.25% 46.25% 46.25%
% vaccinations obtained from public health clinics 22% 22% 22%
% vaccinations obtained from private sector providers 78% 78% 78%
% vaccine waste 4.5% 4.5% 4.5%
Weighted cost per dose + administration$162.61
($128 -$191)$ 209.70
($155 -$250) $277.92***
($255 -$290)
16Other Benchmark Elements
Sources: Shepard et al. Pediatrics. 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/
Ortega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/•Meningococcal disease incidence under vaccination
•Direct and Indirect costs of meningococcal disease
•Acute phase costs and long -term costs
•Productivity loss to deaths and sequelae
•Health related quality -of-life scores for estimating QALYs lost to sequelae
Program impact and cost -effectiveness then calculated by considering
Incremental Cost -effectiveness ratios
Monetary and quality -of-life costs associated with health outcomes
Cost of vaccination program including AEs
Quality of life outcomes
17Components of cost of illness calculation
OutcomeMed care
(mening )Parents’
Work -LossMed care
sequelaeLifetime care
(rehab, long term
care)**Productivity
Loss
No Sequelae (acute
phase√ √
Death √ √ √
Skin scarring √ √ √
Single amput √ √ √ √
Multi amput √ √ √ √ √
Hearing loss √ √ √ √
Neuro seq √ √ √ *** √Acute phase* Lifetime
*Includes caregivers' work time loss and public health response in outbreaks
** Includes special education for neurologic disability, prosthesis & rehabilitation for amputations, etc.
*** Significant neurologic disability lifetime medical costs were calculated and then annualized
Sources: Shepard et al. Pediatrics . 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/
Ortega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/
Selected Cost of Meningococcal -Associated
Events*
Event / Cost Base -case Range for SA
Invasive meningococcal disease
Medical costs $48,983 $24,459 -$87,790
Public health response costs $13,547 $1,791 -$16,008
Value of work time lost by caregivers (acute phase) $4,160
Skin scarring
Medical care $7,436 $6,849 -$11,153
Single amputation
Medical care $23,050 $11,525 -$34,575
Other (prosthesis & rehabilitation) $180,446 $90,222 -$270,668
Value of permanent disability Age-specific
Multiple amputations
Medical care $27,662 $13,830 -$41,491
Other (prothesis & rehabilitation) $216,535 $108,267 -$324,802
Value of permanent disability Age-specific
Hearing loss
Medical care $89,566 $26,190 -$113,441
Value of permanent disability Age-specific
Long -term neurologic disability
Residential care $2,704,703 $923,013 -$3,288,152
Special education $204,014 $123,350 -$245,230
Value of permanent disability Age-specific
Premature death
11-17 yrs $1,657,326
18-24 yrs $1,734,664
* Costs were in 2022 US dollars and were adjusted for their social constant value in the economy using the Gross Domestic Pro duct (GDP) deflator.
Sources: various source and some unit costs were obtained after sequalae specific intermediate estimations  18
19Productivity Loss
•Incurred in cases with premature death or permanent sequelae:
•Acute phase
•Time of work missed Caregiver
•Death
•Labor market earnings + household production*                   Patient
•Neurologic sequelae
•Labor market earnings* Patient  & caregiver
•Multiple amputations
•30% of labor market earnings** Patient
•Hearing loss
•33% of labor market earnings** Patient
*Reported in  Grosse SD, et al . J Med Econ. 2019 Jun;22(6):501 -508.. https://pubmed.ncbi.nlm.nih.gov/30384792/
Values were adjusted to 2022 US$. Age -specific values, US population, 3% discount rate
** Shepard et al. Pediatrics . 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/
Ortega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/
20Health -related Quality of Life QALY Scores*
Base case High Low
Baseline utilities 11 -25 years old ** 0.92
Survivor of IMD without sequalae (first year only) *** 0.91 0.88 0.94
Death 0
Skin scarring 0.95 1.00 0.80
Single amputation 0.70 0.80 0.31
Multiple amputations 0.61 0.71 0.31
Hearing loss/cochlear implants 0.72 0.82 0.64
Neurologic disability 0.06 0.39 0.00
*Several sources cited in: Shepard et al. Pediatrics . 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/
Ortega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/
** Age -dependent EQ -5D-5L Utilities from Jiang, R. et al. Quality of Life Research, 2020:30, 803 -816. https://pubmed.ncbi.nlm.nih.gov/33025373/
*** Assumption based on hospitalization scores (unpublished data from a JIVE Covid utilities study. University of Michigan)
Note: Among survivors, except those without sequelae, the specific score’ reduction is applied for the remaining lifetime of survivor
21Disease Incidence Under Vaccination
For each age group and for each vaccination strategy
MDIvacc= MDIno vacc * [1 -VE*DoPt*Vcov ]
Where:
•MDIvacc = Meningococcal disease incidence under vaccination for each type of vaccine
•MDInovacc = Meningococcal disease incidence without vaccination
•VE = Initial v accine efficacy from each vaccine and dose
•DoPt = Duration of protection factor ( t= time in years after vaccination)
•Vcov = Vaccination coverage for each vaccine and dose
Economic evaluation
Incremental cost -effectiveness ratio ( ICER ) :
𝐼𝐶𝐸𝑅=𝑁𝐶𝑝𝑒𝑛𝑡𝑎−𝑁𝐶𝑆𝑜𝐶
𝐻𝑂𝑆𝑜𝐶−𝐻𝑂𝑝𝑒𝑛𝑡𝑎
Where:
•NCpenta = Net Cost of IMD disease with new interventions
(vaccine program costs)
•NCSoC = Net Cost of IMD disease costs under
Standard of care
•HOpenta = Health outcome using pentavalent (ex., QALYs)
•HOSoC = Health outcome of Standard of Care (ex., QALYs)
Both Cost and QALYs are discounted using:
•t = time years after immunization (t=0, 1, 2,…, T)
•r  = discount rate (3%)
•T = Analytical horizon (age -specific, in years)Number needed to vaccinate (NNV) ratio :
𝑁𝑁𝑉=#𝑉𝑎𝑐𝑐𝑖𝑛𝑒𝑒𝑠
#𝐻𝑂𝑠𝑎𝑣𝑒𝑑
Where:
•# Vaccinees = Number of individuals vaccinated
against IMD during the time frame of the
intervention
•#HOsaved = Number of health outcomes saved or
prevented with vaccination, ex.,
•Acute IMD cases prevented
•Life-years prevented
•lives saved
23Results*
* Preliminary
Expected Cumulative Annual IMD Cases* and Deaths**
without vaccination in 11 –25-years old*
24120400
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Cumulative number of IMD cases ( in logarithms )
Age in yearsMen ABCWY
Men ACWY
Men B
010203040506070
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Cumulative number of IMD deaths
Age in yearsMen ABCWY
Men ACWY
Men B
* Using IMD incidence data from 1996 -2005 (pre -vaccine) for serogroups CWY and 1994 -2013 (pre -vaccine) for serogroup B
** Using CFR data is from NNDSS for 2008 -2020
Cumulative Number of IMD Cases Saved: Vaccination
strategy -and age -specific*
*Estimates from Monte Carlo Simulation
** Rounded to the nearest whole number25StrategyMean**
(5th& 95thpercentiles)
P-P-P229
(191 –273)
Q-P-B228
(190 –278)
P-P-N229
(189 –276)
Q-P-P226
(185 –270)
SoC207
(163 –252)
Q-Q194
(156 –241)
050100150200250300
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Cumulative number of IMD cases saved by Vaccine
Age in yearsP-P-P
Q-P-B
P-P-N
Q-P-P
SoC
Q-Q
B-B
0510152025303540
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Cumulative number of IMD deaths saved by Vaccine
Age in yearsP-P-P
Q-P-B
P-P-N
Q-P-P
SoC
Q-Q
B-BCumulative Number of IMD deaths prevented:
Vaccination strategy -and age -specific*
*Estimates from Monte Carlo Simulation
**  Rounded to the nearest whole number26StrategyMean**
(5th, 95thpercentiles)
P-P-P32
(25 –40)
Q-P-B32
(25 –40)
P-P-N32
(25 –41)
Q-P-P31
(25 –40)
SoC30
(23 –37)
Q-Q27
(21 –36)
Number needed to vaccinated to prevent a case,
save a life, a life -year or a quality -adjusted life year
With
Men ACWY
(Q-Q)With Men B
(B-B) Q-P-B P-P-P
A IMD Case 19,034 292,559 16,144 16,085
A Death 133,981 1,810,451 115,450 115,086
A Life -year 4,644 63,695 4,763 4,745
A QALY 2,609 38,169 2,694 2,682
*   Estimates from Monte Carlo Simulation
Men ABCWY = Potential pentavalent vaccine (P) with serogroups A, B, C ,W and Y
Men ACWY = Quadrivalent vaccine (Q)  for serogroups A,  C, W, and Y ,
Men B =Meningococcal serogroup B vaccine (B)
27
Baseline of SoC: Health outcomes, Vaccine and
Net Costs per ~4M Cohort, Mean (5th,95thPercentile)*
No Vaccine BCWYPrevention with
Men ACWY  (Q -Q)
Vaccine & Net CostsPrevention with
Men B  (B -B)
Vaccine & Net Costs SoC
IMD Cases428
(296 -604)194
(156 –241)13
(7 –21)207
Deaths68
(44 -95)28
(21 –36)2
(1 –4)30
Life years ***1,938
(1252 -2,701)796
(592 –1,035)58
(31 –98)854
QALY’s ***3,306
(3,084 -4,513)1,416
(1,090 –1,800)97
(53 –164)1,513
Vaccination program costs
(in Millions $) 0.0$1,120.4
(826.9 –1,471.5)$1,492.7
(1,061.2 –2,18.6)$2,613.0
Total net cost of illness
(in Millions $) ***$270
($178 -$379)$997.5
(667.0 –1,325.5)$1,485.0
(1,053.8 –2.011.3)$2,482.5
*Estimates from Monte Carlo Simulation
**  Health outcomes were rounded to the nearest whole number
**Discounted at 3%28
Health outcomes saved and Net Cost per 4M Cohort of
11yrs followed until 25yrs: Mean (5th, 95thPercentile)*
SoCQ-P-B
(for Pico 1) P-P-P Q-QP-P-N
(for Pico 2)
IMD Cases207 229
(190 –278)229
(191 –273)194
(156 –241)229
(189 –276)
Deaths30 32
(25 –40)32
(25 –40)27
(21 –36)32
(25 –41)
Life years saved ***854 775
(585 –1,000)777
(584 –995)796
(590 –1,035)778
(577 –1,012)
QALY’s saved***1,513 1,370
(1,059 –1,7281,376
(1,065 –1,762)1,417
(1,090 –1,800)1,375
(1,058 –1,742)
Vaccination program
costs (in Millions $) $2,613.0 $2,129
(1,870 –2,425)$2,788.8
(2,602.5 –2,983)$1,120.4
(826.9 –1,472)$1,915.9
(1,788 –2,049)
Total net cost of illness
(in Millions $) ***$2,482.5 $1,986.4
(1,695 –2,265)$2,645.6
(2,469 –2,847)$968.2
(703.0 –1,348)$1,773
(1,643 –1,906)
29*   Estimates from Monte Carlo Simulation
**  Health outcomes were rounded to the nearest whole number
** Discounted at 3%
Incremental Cost per QALY saved by each vaccination
strategy when compared to No vaccination*
*Estimates from Monte Carlo Simulation, numbers were rounded to nearest thousand
The pink -shaded areas highlight comparison that would corroborate the incremental analysis results  30$550,000$17,082,000
$1,498,000
$1,126,000
100,0001,000,00010,000,000100,000,000
Q-Q B-B SoC P-P-NCost per QALY saved ( in logarithms )
$1,498,000
$1,290,000$1,517,000$1,775,000
700,0001,200,0001,700,0002,200,0002,700,000
SoC Q-P-B Q-P-P P-P-PCost per QALY saved$1,498,000$17,082,000
$550,000$1,126,000
100,0001,000,00010,000,000100,000,000
SoC B-B Q-Q P-P-NCost per QALY saved ( in logarithms )
Incremental Cost -Effectiveness Analyses for QALYs
and Life -years saved ( in thousands $ )
*Estimates from Monte Carlo Simulation  (Discounted at 3%)
** the $/LY gained of P -P-N vs SoC strategy could be marginally cost-saving: Mean $/LY <0, but its 5thand 95thpercentiles from simulation range from <0 to costly
Note: SoC            = Standard of care = one quadrivalent dose 11 -12yrs and second at 16yrs (= Q -Q) and2 doses Men B at 16yrs (= B -B)
Cost-saving          = a strategy could be said to be dominant when is cost -saving 31Q-P-B vs. SoC
(Pico 1)P-P-P vs. SoCP-P-N vs. Q -Q
(Pico 2)
ICER QALY saved*Q-P-B
is cost -saving
(Cost <0)P-P-P is
incrementally costly
$1,455P-P-N
Is incrementally costly
$2,936
ICER LY saved*Q-P-B
is cost -saving
(Cost <0 ) P-P-P could be cost saving
(Cost ≤0)**
(Range from cost -saving to costly)P-P-N
is incrementally costly
$4,563 Q-P-B vs.
No vaccinationSoC vs
No vaccinationP-P-P vs
No vaccinationP-P-N vs.
No vaccinationQ-Q vs.
No vaccination
$/QALY saved*$1,256 $1,461 $1,730 $1,096 $534
$/ LY saved$2,563 $2,908 $3,401 $2,279 $1,254
Probability of Incremental Cost -Effectiveness ratio
per QALY saved: Q -P-B vs SoC: $/QALY<0 (Pico 1)
32-8.12 -0.58
5.0% 5.0% 90.0%
0.00.20.40.60.81.0
-10
-8
-6
-4
-2
0
2
4
6
Values in Millions ($)Q-P-B-vs-SoC: Cumulative Probability of ICER per QALY saved*
*Estimates from Monte Carlo Simulation using a sample of 1000 iterations (Costs were discounted at 3%)
Range are 5thand 95thpercentiles •Both 5thand 95th
percentiles are
negative (i.e., cost
saving)
•More than 95% of the
iterations were
negative (i.e., cost
saving)
Sensitivity of Incremental Cost -Effectiveness ratio per
QALY saved: P -P-N vs Q -Q  $2.9M/QALY gained (Pico 2)
33

34Strengths and Limitations
Strengths
•Complex modeling
•Explicit use of incidence and CFR surveillance data for Men BCWY vaccine -
containing serogroups
Limitations
•Data on vaccine effectiveness from pentavalent Men BCWY are from clinical trials
•Hard to ascertain decrease in IMD incidence rates due to natural decline trend vs.
vaccine induced decline
•Variability of vaccine uptake per type of vaccine
35Conclusions
•Disease rates and vaccine cost drive the incremental analyses
•Although additional cases could be prevented by all vaccination
strategies, they do it at different costs per health outcome
•Most strategies with one or more doses of the Men ABCWY vaccine would
save more or equal number of cases, but they do at a much higher costs per
QALY saved when compared to the standard of care.
•The exception is the Q -P-B, which included one dose of Men ABCWY in
substitution of the second dose of Men ACWY and first dose of Men B.
•Q-P-B  could be incrementally cost -saving (ICER QALY <0) relative to the
standard of care
•Using last 10 years of epidemiology data and current (or proposed)
vaccine prices increase the cost of all strategies compared to previous
analyses
End of Presentation

Incidence rate of IMD for serogroups CWY 1996 -
2005 and 1996 -2020 by age per 100,000
0.000.200.400.600.801.001.201.401.60
=<10 11 12 13 14 15 16 17 18 19 20 21 22 >=23IMD incidence rate for serogroups CWY per 100,000
AgeMean CWY 1996-2005
Median CWY 1996-2005
Mean CWY 1996-2020
Median CWY1996-2020
Incidence rates from 1996 -2005 for the Pre vaccine Era are from the ABC core surveillance
Incidence rates from 1996 to 2020 combined data from ABC and NNDSS.  37
Incidence rate of IMD for serogroup B before
and during vaccine era by age per 100,000
00.050.10.150.20.250.30.35
11-12 years 13-14 years 15-16 years 17-18 years 19-20 years 21-22 years 23-24 yearsIMD incidence rate for serogroup B  per 100,000
AgeABC-1994-2013
2014-2016
2017-2019
2020-2022 Pre
Data from 1994 -2013 are from the ABC core surveillance, Data from 2014 -2019 are from the NNDSS.
Data from 2020 -2022 also from NNDSS is preliminary 38
Incidence rate of IMD for serogroups CWY  before
and during vaccine era by age per 100,000
0.010.101.0010.00
=<10 11 12 13 14 15 16 17 18 19 20 21 22 >=23IMD incidence per 100,000(n logarithms)
AgeMean CWY 1996-2005
Median CWY 1996-2005
Mean CWY 2005-2020
Median CYW 2005-2020
39

Summary: The Cost -effectiveness of a Potential Pentavalent  Meningococcal Conjugate Vaccine (Men ABCWY)  versus the Current Men ACWY and Men B  vaccines for US Adolescents  Ismael R. Ortega -Sanchez, PhD CDC/NCIRD ACIP meeting, June 23, 2023 Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily  represent the views of the Centers for Disease Control and Prevention. 1  2Conflict of Interest CDC/NCIRD collaborators:  All collaborators, No conflict of…