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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?