Mpox (monkeypox), Vaccines

Introduction

• In October 2023 CDC moved from earlier outbreak-based recommendations to standing recommendations.
• 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.
  • Jynneos will be available via the commercial market beginning in 2024.
• 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: 
  • At least 1 sexually transmitted disease 
  • More than one sex partner 
  • Sex at a commercial sex venue 
  • Sex in association with a large public event in a geographic area where mpox transmission is occurring 
• Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who
  in the past 6 months have had one of the following: 
  • Sexual partners of persons with the risks described in above 
  • Persons who anticipate experiencing any of the above 
  • Persons deemed at risk by health authorities in outbreak situations including travelers.
• Healthcare workers:  Should not receive Jynneos unless they have a sexual risk factor as above.

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.

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 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 66% - 89% for 2 doses and 36-75% for 1 dose.
  • 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 

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.

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

• 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 2-8^o C for 4 weeks after thawing from -20^oC 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:
  • Monkeypox
• Other resources:
  • U.S. CDC Vaccine Considerations: Mpox
  • U.S. CDC  MMWR (pre-outbreak) on Jynneos use for mpox