Mpox (monkeypox), Vaccines

by David O. Freedman, M.D. last updated 2022-11-29 15:29:23.086709-05:00 © Antimicrobial Therapy, Inc.
Vaccinia, Modified Vaccinia Ankara, monkeypox,


  • Mpox will replace monkeypox as the disease name in late 2023 with the transition to begin immediately.
    • Monkeypox virus continues, at present, to be the name of the causative agent of mpox.
  • Jynneos (non-replicating) 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 although at least 100 million doses are in the Strategic National Stockpile
  • Jynneos is in constrained supply until sometime in 2023
  • Supply of both vaccines is completely controlled by CDC and local public health authorities.  Neither vaccine has ever been sold commercially

Indications for Vaccination

  • No mpox vaccine 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 and guidelines for use may differ in some states from CDC recommendations
  • ACIP guidelines for pre-exposure vaccination were developed prior to the 2022 outbreak

Preexposure vaccination should be given to:

  • Research-laboratory and clinical-laboratory personnel working with orthopoxviruses or clinical investigators working recombinant vaccinia-virus vaccines
  • Designated response team members (vaccination may be offered at the discretion of public health authorities)

Preexposure vaccination 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 for 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).  Guidance will evolve as the outbreak progresses and will be updated as it changes. State health authorities have discretion to categorize risk situations to a level mandating vaccination in designated areas. See CDC Interim Guidance (10/19/2022)
Component Definition Eligible Populations
Post-exposure Prophylaxis (PEP) Vaccination after known 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
Expanded 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 aware that a recent sex partner within the past 14 days was diagnosed with mpox
  • Certain 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
Pre-exposure Prophylaxis (PrEP) 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 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).

Dose and Schedule

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) ≥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 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

  • If indicated administer to persons with 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=5,000)
    • average mpox incidence (per 100,000) among unvaccinated persons was 14.3 (95% CI = 5.0-41.0) times that among persons who received 1 dose of JYNNEOS vaccine (full or fractional dose) ≥14 days earlier. MMWR 71(40):1278, 10/9/2022
    • Peak antibody levels 14-days after dose 2 (day 42).  In vaccinees (n=7339) 90 breakthroughs before day 42 and 2 beyond day 42 (JAMA online 09/30/2022).


  • 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 subcutaneous (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 as a result of HIV or AIDS, 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


  • Adverse reaction rates following vaccination with Jynneos (dose 1, 2, or booster) were similar with each dose.
  • Most commonly injection-site reactions (pain [85%], redness [61%], swelling [52%], induration [46%], and itching [43%]), muscle pain (43%), headache (35%), fatigue (30%), nauseas (17%), and chills (10%).
  • Serious adverse events occurred in 1.5% of Jynneos recipients versus 1.1% of placebo recipients; attributable cardiac adverse events (all nonserious) occurred in 0.08% of Jynneos recipients.
  • Elevated troponin levels (> 2 times the upper limit of normal) were reported in 3 of 3,003 subjects but shown to be not causally related to vaccination.


  • 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.
  • Whether Jynneos is excreted in human breast milk is unknown. Receipt of Jynneos is not a contraindication to breastfeeding

Immunocompromised / HIV

  • Immunogenicity of Jynneos in HIV  (Open Forum Infect Dis, 2015 Apr; 2(2):ofv040).
  • 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.  A lyophilized presentation to be available as early as 2023 is not yet FDA-approved
  • 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