Introduction
- As of October 2023, >30,000 US cases with ~10 new incident cases per week.
- Mpox has replaced monkeypox as the disease name.
- 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 at present.
- As of April 2024 Jynneos is available commercially through usual vaccine wholesalers.
- Public health advice should be sought prior to use for smallpox prevention, also an FDA-approved indication.
- As of April 2024 Jynneos is available commercially through usual vaccine wholesalers.
- 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 is not available and has not been used in the US in recent years.
Indications for Vaccination
- Persons >18 yrs with risk factors should receive 2 doses of Jynneos 28 days apart.
- Persons at risk:
- Known or suspected exposure to someone with mpox.
- Sex partner in the past 2 weeks who was diagnosed with mpox.
- Gay, bisexual, or other man who has sex with men or a transgender, nonbinary, or gender-diverse person who in the past 6 months has had any of the following:
- A new diagnosis of one or more sexually transmitted diseases (e.g., chlamydia, gonorrhea, or syphilis)
- More than one sex partner
- Any of the following in the past 6 months:
- Sex at a commercial sex venue (like a sex club or bathhouse)
- Sex related to a large commercial event or in a geographic area (city or county for example) where mpox virus transmission is occurring
- A sex partner with any of the above risks.
- Anticipation of any of the above scenarios including travelers to outbreak areas who meet the above criteria
- Risk of occupational exposure to orthopoxviruses (e.g., certain people who work in a laboratory or a healthcare facility).
Vaccination prior to exposure should also be offered to:
- 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)
- HCWs who administer ACAM2000 replicating vaccinia virus vaccine.
- 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
Dose and Schedule
- Recent mpox infection precludes need for an initial or a second dose of Jynneos.
- Based on US CDC experience to date, no recommendation for a third JYNNEOS dose at this time, including for persons with HIV or severe immunocompromise.
- 2022 EUA still in effect for 12-17 yrs of age.
- NIH trial underway for full approval
- 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). (Mpox). 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 (EUA available for 12-17 yrs). Use VIGIV for children <6 mos. | ≥1 yr |
Dose and Route | FDA approved: 0.5 mL sc (deltoid preferred). | FDA approved: 2.5uL percutaneous2 |
Primary Schedule - routine |
0, 4 wks (up to 5 wks preferred); gives as soon as possible otherwise) | Single dose |
Primary Schedule - accelerated |
None | 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.
2 One drop into deltoid using 15 punctures with a special bifurcated needle by specially trained vaccinators who must be themselves vaccinated
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.
Jynneos
- 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 2024 experience
- Peak antibody levels 14-days after dose 2 (day 42)
- VE ranges from 66% - 89% for 2 doses and 36-75% for 1 dose.
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US data as of May 1, 2024 (MMWR 2024, 73:460).
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271 (0.8%) of 32,819 US mpox cases occurred among persons who were fully vaccinated (2 Jynneos doses).
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In a sample of jurisdictions, 187 Mpox infections were reported among 188,907 full vaccinees for a 0.1% infection rate.
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Cases occurred a median of 266 days after receipt of dose 2 (range = 14–621 days; IQR = 64–420 days).
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Innsufficient data was available for stratification by HIV status.
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ACAM2000
- 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
Choice
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).
ACAM2000:
- 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.
Interchangeability
- 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.
- Persons who received dose 1 of Jynneos i.d. during the mPox emergency may receive dose 2 sc
- In case of another outbreak and a vaccine shortage, persons may receive dose 2 i.d. regardless of route of administration of dose 1.
Toxicities
Contraindications
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.
ACAM2000
- 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
Precautions
- 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
Jynneos
- US outbreak experience: All AE's 600/million doses; Serious AE's 22/million doses.
- Myocarditis cases not above population background..
- No unexpected adverse effects.
- No SAE's in IND group <18 yrs of age.
ACAM2000
- 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.
- Administration of JYNNEOS should be delayed (no data on safe interval) if VIGIV was recently administered; this is an uncommon scenario.
Special Populations
Pregnancy, Breastfeeding
- No recommendation at present but pregnant persons with risk as above MAY receive Jynneos.
- 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
Comments
- Typical travelers to outbreak areas of Africa who do not meet risk criteria above are not currently recommended for vaccination.
- Preventive behaviors include avoidance of: sex or intimate contact, ill persons, health care facilities to the extent possible, and so-called bushmeat.
- 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 is not yet FDA-approved does not require ultra-low freezers. Vaccine https://pubmed.ncbi.nlm.nih.gov/36460535/
- 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: