Mpox (monkeypox), Vaccines

by David Freedman last updated Jul 10, 2023 12:41 PM © Antimicrobial Therapy, Inc.
Vaccinia, Modified Vaccinia Ankara, monkeypox,


  • U.S. CDC Mpox vaccination interim clinical considerations.
  • As of February 2023, >86,000 cases in 110 countries with few new incident cases.
    • ACIP (February 2023);  Mpox vaccination (2 doses SC)  is recommended on an ongoing basis to people with the highest potential for exposure to mpox during an outbreak.
      • outbreak is defined by local health authorities and can include just a single case.
      • US outbreak is currently considered ongoing and vaccination of before exposure vaccination (see Table below) should continue especially for persons attending summer 2023 pride festivals.
    • Cumulative cases: US 30,193 (32 deaths);  Brazil 10,808 (15);  Spain 7,538;  France 4,128;  Colombia 4,080.
  • Mpox will replace monkeypox as the disease name in late 2023.
    • Monkeypox virus continues, at present, to be the name of the causative agent of mpox.
    • Clade I (previously Congo Basin Clade)
    • Clade II (previously West African Clade)
  • Jynneos (non-replicating live virus) FDA approved since 2019 is the preferred vaccine given the current high levels of HIV in MSM predominantly affected in the current (2022) outbreak.
  • ACAM2000, a traditional vaccinia virus live replicating virus vaccine has a high rate of myocarditis and some life-threatening adverse effects.
    • >100 million doses are in the Strategic National Stockpile.
    • For practical purposes has not been used and is not available in the US in the current outbreak.
  • Jynneos remains in constrained supply in the US.
    • 1.2 million doses administered in US as of  February 2023.
    • US government supply of finished vials expected to reach 7 million by mid-2023.
  • Supply of both vaccines is completely controlled by CDC but local public health authorities have control over local use guidelines.
    • No mpox vaccine has ever been commercially available in the US

Indications for Vaccination

Vaccination prior to exposure should be given to:

  • ACIP guidelines herein for pre-exposure vaccination were developed prior to the 2022 outbreak
  • Research-laboratory and clinical-laboratory personnel working with orthopoxviruses or clinical investigators working recombinant vaccinia-virus vaccines
  • Response team members (designation at the discretion of local public health authorities)

Vaccination prior to exposure should be offered to:

  • HCWs who administer ACAM2000 replicating vaccinia virus vaccine or care for patients infected with replication-competent orthopoxviruses based on shared clinical decision-making. 
  • Residents of mpox-endemic areas 
  • Travelers to high-risk areas during outbreak situations, especially HCWs.
  • Caregivers who are close contacts of persons with monkeypox infection in either endemic or nonendemic areas

CDC Guidance for Outbreaks

  • Postexposure vaccination (within 4 days of exposure; but up to 14 days).  
  • Discretion for categorization of risk situations defining an outbreak is made by state and local heath authorities. See CDC Interim Guidance (Last updated: 10/19/2022)
  • Mpox vaccination (2 doses SC)  is recommended on an ongoing basis to people with the highest potential for exposure to mpox during an outbreak.
    • Other circumstances for vaccination include ongoing risk of introduction of mpox into a community due to disease activity in another geographic area.

Component Definition Eligible Populations
Post-exposure Prophylaxis (PEP) Vaccination after known or presumed exposure to monkeypox virus
  • People who are known contacts to someone with mpox who are identified by public health authorities, for example via case investigation, contact tracing, or risk exposure assessment
  • People who are known contacts to someone with mpox who are identified by public health authorities, for example via case investigation, contact tracing, or risk exposure assessment
  • People who are aware that a recent sex partner within the past 14 days was diagnosed with mpox
  • Gay, bisexual, or other men who have sex with men, or transgender or nonbinary people, who have had any of the following within the past 14 days: sex with multiple partners (or group sex); sex at a commercial sex venue; or sex in association with an event, venue, or defined geographic area where monkeypox virus transmission is occurring
Vaccination prior to exposure Vaccination before exposure to monkeypox virus
  • People in certain occupational exposure risk groups*
  • Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who in the past 6 months have had
    • A new diagnosis of one or more nationally reportable sexually transmitted diseases (i.e., acute HIV, chancroid, chlamydia, gonorrhea, or syphilis)
    • More than one sex partner
  • People who have had any of the following in the past 6 months:
    • Sex at a commercial sex venue
    • Sex in association with a large public event in a geographic area where monkeypox virus transmission is occurring
  • Sexual partners of people with the above risks
  • People with HIV infection or other causes of immunosuppression who have had recent or anticipate potential mpox exposure.
  • People who anticipate experiencing the above risks
  • Exceptions to 2-dose series (give 1 dose only)  in the 2022 outbreak
    • Monkeypox breakthrough after JYNNEOS dose 1. 
      • give dose 2 to immunocompromised persons in this category.
    • Monkeypox since May 17, 2022 (natural immunity).

CDC Guidance for Contacts in the Community

  • High Degree of Exposure:  Give PEP
    • Exposure Characteristics
      • Contact between an exposed person’s broken skin or mucous membranes with skin lesions or bodily fluids from a mpox case -OR-
      • Any sexual or intimate contact involving mucous membranes (e.g., kissing, oral-genital, oral-anal, vaginal, or anal sex (insertive or receptive)) with a mpox case -OR-
      • Contact between an exposed person’s broken skin or mucous membranes with materials (e.g., linens, clothing, objects, sex toys, shared food) that have contacted the skin lesions or bodily fluids of a mpox case  
  • Intermediate Degree of Exposure: PEP Case by Case
    • Exposure Characteristics
      • Being within 6 ft for a total of 3 hours or more (cumulative) of an unmasked mpox case without a surgical mask or respirator -OR-
      • Contact between an exposed person’s intact skin with the skin lesions or bodily fluids from an mpox case -OR-
      • Contact between an exposed individual’s intact skin with materials (e.g., linens, clothing, sex toys) that have contacted the skin lesions or bodily fluids from a person with mpox -OR-
      • Contact between an exposed person’s clothing with the person with mpox case’s skin lesions or bodily fluids, or their soiled linens

Dose and Schedule

  • Recent mpox infection precludes need for an initial or a second dose of Jynneos.
  • Based on US CDC experience to June 2023, no recommendation for third JYNNEOS dose at this time, including for persons with HIV or severe immunocompromise.
  • No efficacy data yet in current outbreak for <18 yrs of age.
  • No studies or data on dosing in children <6 yrs.
Tradename (Manufacturer) Jynneos (Bavarian Nordic); labelled as Imvamune or Imvanex outside US ACAM2000 (Emergent Biosolutions)
Vaccine (type, CDC acronym)1
Replication-deficient vaccinia virus (Modified vaccinia Ankara). FDA and EMA approved for both mpox and smallpox. Replication competent vaccinia virus (cloned NYCBOH strain). FDA approved for smallpox only. IND in place for mpox
Age ≥18 yrs (IND available for <18 yrs). Use VIGIV for children <6 mos. ≥1 yr
Dose and Route FDA approved: 0.5 ml sc (deltoid preferred).  EUA: 0.1 ml id for dose sparingwhenever possible during 2022 outbreak if >18 yrs of age. Discuss preference with patient. FDA approved: 2.5ul percutaneous3
Primary Schedule - routine
0, 4 wks (up to 5 wks preferred); gives as soon as possible otherwise) Single dose
Primary Schedule - accelerated
None4 None

1st Booster

Jynneos preferred for persons previously given ACAM2000

2 yrs if continued occupation exposure to variola or monkeypox virus; 10 years if exposure is to vaccinia or cowpox 3 yrs if continued occupation exposure to variola or monkeypox virus; 10 years if exposure is to vaccinia or cowpox
Subsequent Booster 2 or 10 years as above 3 or 10 years as above

1Neither vaccine contains variola (smallpox) or monkeypox virus and cannot spread or cause mpox or smallpox.

2Need to use 0.5 ml vial for 5 doses, no human data on fractional id dosing of Jynneos but traditional vaccinia vaccine approved at this dose against smallpox for use in emergencies.  Use only special low dead space syringes in order to get 5 doses per vial.

3 One drop into deltoid using 15 punctures with a special bifurcated needle by specially trained vaccinators who must be themselves vaccinated

4Delay of dose 2 being considered during vaccine shortage. Some supportive antibody data from trials (see Efficacy above) shows peak nAbs against vaccinia after a complete 2-dose course of Jynneos are 2-fold higher than after a completed single-dose course of ACAM2000. Two weeks after a single dose of either vaccine, at a time when ACAM2000 produces a "take," nAb titers against vaccinia virus are equal with either vaccine. However, ACIP concluded that Jynneos provides a small increase in disease prevention compared to ACAM2000.

Efficacy, Duration of Protection

  • Prior smallpox vaccination provides long-term immunity to mpox in ~80% of vaccinees.
  • However, if otherwise, indicated administer mpox vaccine to persons with a history of previous smallpox vaccine; mpox breakthroughs have occurred in such persons.


  • In primates,  2-doses resulted in a 100% protective efficacy against death versus 0% to 40% survival in controls. 
  • In humans, a single dose of Jynneos induced  titers at 2 weeks that leveled off from day 14 to day 28.
  • Peak antibody levels 14-days after dose 2.
  • In animals a single dose may provide post-exposure protection,
  • Peak vaccinia nAbs at day 42 from initiation that were 2-fold higher than those stimulated by a single dose of ACAM2000
  • An open-label efficacy trial in HCWs at specific risk in DRC resulted in no monkeypox disease (n = 1,000) in an area with annual monkeypox incidence rate of 4.4/10,000 [17.4/10,000 among HCWs]).
  • Duration of immunity after either 1 or 2 doses not known.  
  • US 2022 outbreak experience (n=>10,000 multiple studies).
    • Peak antibody levels 14-days after dose 2 (day 42)
    • Highest protection provided by 2 doses, regardless of SC or ID; VE similar SC vs ID 
    • VE ranges from 76% - 83% for 2 doses and 65%-86% for 1 dose.
    • Mpox incidence among unvaccinated persons 9.6X compared to 2 vaccine doses and 7.4X compared to 1 dose with no difference between sc and id routes. MMWR 2022;71:1560
    • Further research needed on immunocompromised
  • 2020 Israeli experience with single dose Jynneos VE=86% after at least 90 d follow-up. Nat Med 2023; Jan31, 1-5 (online ahead of print)


  • Historic African data from the early 1980s indicates that persons vaccinated against smallpox (Dryvax, ACAM2000 precursor) had 85% protection against mpox; duration of the cross-protection was not studied.
  • Data from 2 NHP studies indicate that pre-challenge vaccination resulted in a protective efficacy against death of 100% vs 0% survival in controls.
  • nAbs peak at day 28


Jynneos (vaccine of choice):

  • No history or screening is required because Jynneos is safe to use in all persons, including immunocompromised and HIV 
  • Compared to ACAM2000 (a replication-competent vaccine), Jynneos (a replication-deficient vaccine), has fewer contraindications
  • Administration is via the standard SC route
  • Cardiac (myocarditis or pericarditis) or other toxicities much lower risk
  • Special injection-site care of a replicating virus-containing scab is not required (no scab is formed).


  • A successful single-dose primary series results in a "take" at the site of the vaccination as a measure of proven protective efficacy.  However, the lesion may take up to 6 weeks or more to heal.
  • In case of imminent traveler departure, a completed single-dose primary series may be more effective than a single dose of Jynneos.
  • Replication-competent vaccine can be diluted to increase vaccine supply.
  • Less stringent freezer requirements
  • Is a derivative of Dryvax, a previous vaccinia-virus vaccine used with a track record of successfully eradicating smallpox; Jynneos has no proven track record in public health settings.


  • Jynneos is preferred over ACAM2000 for monkeypox due its safety profile. 
    • The vaccines are interchangeable if needed for booster doses.  A primary 2 dose series that is begun with Jynneos should be completed with Jynneos.




  • Anaphylactic reaction to a previous dose of either Jynneos (gentamicin, ciprofloxacin, egg protein) or ACAM2000 or a vaccine constituent contraindicates further vaccination with that vaccine or any vaccine containing that constituent. In an outbreak situation the risk for severe mpox may outweigh the risk of vaccination.
  • No other contraindications exist for the administration of Jynneos.


  • Non-emergent vaccination of persons or their close contacts with atopic dermatitis or other exfoliative skin conditions
  • Persons who are immunocompromised (HIV included), autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies or their close contacts. 
  • Women who are pregnant or breastfeeding or might become pregnant within 28 days after vaccination
  • Persons with 1 or more significant underlying heart conditions


  • Caution should be used when considering administration of Jynneos (preferred) or ACAM2000 to children and adolescents aged < 18 years due to risk of myopericarditis.
  • Counsel on myopericarditis in persons with 3 or more cardiac risk factors prior to Jynneos.
  • Moderate or severe acute illness, with or without fever; defer until resolved.

Adverse Effects


  • US outbreak experience:  All AE's 600/million doses; Serious AE's 22/million doses.
  • Myocarditis 7 cases not above population background..
  • No unexpected adverse effects.
  • No SAE's in IND group <18 yrs of age.


  • One of every 3 persons may feel ill enough to miss work, school, or recreational activities or have trouble sleeping.
  • Myocarditis and pericarditis (with signs/symptoms of chest pain, elevated troponin/cardiac enzymes, or ECG abnormalities) have been reported following smallpox vaccination at a rate of 5.7 per 1,000.
  • Eczema vaccinatum (vaccinia), postvaccinial encephalitis, progressive vaccinia, and several other potentially fatal reactions are frequent enough to be of concern

Drug Interactions

  • No data on co-administering Jynneos with other vaccines.
    • May administer without regard to timing of most other vaccines.
  • Administration of Jynneos or ACAM2000 should not be delayed in the setting of an outbreak because of recent receipt of an mRNA COVID-19 vaccine; no minimum interval is necessary.
  • For persons already vaccinated with Jynneos or ACAM2000, consider delaying administration of an mRNA COVID-19 or Novavax vaccine by at least 4 week

Special Populations

Pregnancy, Breastfeeding

  • No contraindication to Jynneos in pregnancy; nonreplicating vaccine is preferred for use over replicating vaccines for preexposure or postexposure vaccination.
    • Unknown if Jynneos given during pregnancy during 2022-3.
  • Whether Jynneos is excreted in human breast milk is unknown but is non-replicating.
    • Jynneos is not a contraindication to breastfeeding

Immunocompromised / HIV

  • Immunogenicity of Jynneos in HIV  (Open Forum Infect Dis, 2015 Apr; 2(2):ofv040).
  • People with HIV or other causes of immunosuppression who have had recent or anticipate potential mpox exposure are a priority for vaccination before exposure.
  • No absolute contraindications to vaccination exist if a person has been exposed to monkeypox virus.
  • Persons with severe immunocompromise exposed to monkeypox virus may not benefit from vaccination but Jynneos is safe if antivirals are not immediately available.
  • Persons with weakened immune systems and their close personal or household contacts should not receive ACAM2000


  • CDC Guidance for administration errors (dose too low/high, wrong intervals, wrong route):
  • Current Jynneos presentation is frozen liquid with optimal long-term storage at -90°C to -70°C  Lower temperatures shorten shelf-life.  
    • may be stored locally at 2-8o C for 4 weeks after thawing from -20oC at longer term storage points
  • A lyophilized presentation to be available as early as 2023 is not yet FDA-approved does not require ultra-low freezers.  Vaccine
  • ACAM2000 can be stored at -25°C to -15°C for long periods
  • LC16-Kaketsuken (LC16m8; KM Biologics): Japan is a minimally replication-competent vaccinia-virus vaccine approved and available in Japan for both children and adults.
  • CNJ-016 (VIGIV; Emergent BioSolutions) is a purified IgG fraction containing anti-vaccinia antibodies that is approved for complications from vaccinia virus in ACAM2000 (e.g., eczema vaccinatum; progressive vaccinia; severe generalized vaccinia) especially in immunocompromised persons.
    • VIGIV may be considered for prophylactic use in severely immunocompromised persons with exposure to monkeypox virus.
    • No VIGIV is commercially available in the US
    • All stocks are owned by the Strategic National stockpile
    • CDC is responsible for allocation to state and other public health authorities for distribution
  • See related topic:
  • Other resources:
    • U.S. CDC Vaccine Considerations: Mpox
    • U.S. CDC  MMWR (pre-outbreak) on Jynneos use for mpox