National Center for Emerging and Zoonotic Infectious Diseases

Considerations for long-term protection against mpox

Advisory Committee on Immunization Practices

June 23, 2023

Agam 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 enzymelinked 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

vaccination

Prior 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, 2023

0

20

40

60

80

100

Any Reaction Pain Edema Pruritis Induration Erythema Tenderness Other

Percent

Dose 1 Dose 2 Dose 3

Select 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. population

Current Knowledge

CDC’s DRC study: Study of HCP shows 

increased adverse events among 

recipients of 3rd dose at 5 years after 

primary series
Safety of third dose of JYNNEOS in persons with HIV

Overton 2020 Vaccine

Limitation

Small numbers of total subjects; 

only 30 patients received third 

dose; difficult to know likelihood of 

increased adverse events

Current Knowledge

Study of persons with HIV (CD4 100–

500) shows increased adverse events 

(albeit not significant) among 

recipients of third dose at week 12

0

20

40

60

80

100

Any AE Grade 3 AE Site Pain Pruritis Induration Myalgia Fatigue

Percent

2 doses, standard volume 2 doses, double volume 3 doses, standard volume

Select vaccine-associated adverse events, by dose, among persons with HIV in the United States (n=87 for 1st and 

2

nd doses, 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/mm3

Limitation

▪ 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/mm3

Limitation

▪ 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, 

immunocompromised 22 52 51.0% (-27.6–81.2)

Full vaccination VE, 

immunocompromised 9 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 doses

Limitation

▪ 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 extrapolated 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 dose

Current Knowledge

▪ >10,000 mpox cases among persons with 

HIV; however no 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 Pathology

Questions and Comments?