Introduction
Jynneos (Smallpox and Monkeypox Vaccine, Live, Non-Replicating) is a third-generation vaccine developed by Bavarian Nordic for active immunization against smallpox and monkeypox disease in adults. Approved by the FDA in 2019, it represents a significant advancement in biodefense preparedness and emerging infectious disease response. Unlike earlier smallpox vaccines, Jynneos uses a non-replicating modified vaccinia Ankara (MVA) virus, making it suitable for populations who cannot receive traditional replicating vaccinia virus vaccines.
Mechanism of Action
Jynneos contains a live, attenuated vaccinia virus (Modified Vaccinia Ankara - MVA strain) that has been engineered to lose its ability to replicate in mammalian cells. The vaccine stimulates both humoral and cellular immune responses by expressing multiple vaccinia virus antigens. Upon administration, antigen-presenting cells process these antigens and present them to T-cells, initiating a robust immune response that generates neutralizing antibodies and memory T-cells against orthopoxviruses, including variola (smallpox) and monkeypox viruses.
Indications
FDA-approved for:
- Active immunization for prevention of smallpox disease in adults 18 years and older
- Active immunization for prevention of monkeypox disease in adults 18 years and older
Also authorized under Emergency Use Authorization for:
- Expanded age groups during monkeypox outbreaks
- Intradermal administration to expand vaccine supply
Dosage and Administration
Standard regimen: 0.5 mL administered subcutaneously as two doses four weeks apart Alternative regimen (EUA): 0.1 mL administered intradermally as two doses four weeks apart Reconstitution: No reconstitution required - supplied as frozen suspension in single-dose vials Storage: Store frozen at -25°C to -15°C; thawed vaccine can be refrigerated at 2°C to 8°C for up to 12 weeks Special populations:- Immunocompromised patients: No dose adjustment required
- Geriatric patients: No specific recommendations
- Renal/hepatic impairment: No studies available
Pharmacokinetics
Absorption: Following subcutaneous administration, the non-replicating virus is taken up by antigen-presenting cells at the injection site Distribution: Localized immune response with systemic antibody production Metabolism: Degraded through normal protein catabolic pathways Elimination: Clearance occurs through immune-mediated mechanisms and normal catabolic processes Immunogenicity: Neutralizing antibodies detectable within 14 days after first dose, with peak response occurring 2 weeks after second doseContraindications
- History of severe allergic reaction (e.g., anaphylaxis) to any vaccine component
- Previous severe allergic reaction to a prior dose of Jynneos vaccine
Vaccine components include: tromethamine, sodium chloride, sucrose, L-histidine, L-histidine hydrochloride monohydrate, disodium edetate dihydrate, and water for injection
Warnings and Precautions
Myopericarditis: Cases have been reported following vaccination; monitor for symptoms including chest pain, palpitations, or dyspnea Vaccine effectiveness: Immunogenicity and effectiveness in immunocompromised persons may be diminished Acute illness: Consider deferring administration in persons with moderate or severe acute illness Syncope: Can occur following vaccination; observe patients for 15 minutes after administration Limitations: Data not available for use in pregnancy, breastfeeding, or children under 18 years (except under EUA)Drug Interactions
Immunosuppressive therapy: May diminish immune response to vaccine; consider deferring vaccination until immunosuppression is reduced Concurrent vaccines: Limited data available; the CDC recommends administration simultaneously with or separated by any interval from other vaccines Antiviral medications: Theoretical potential for reduced immune response if administered concurrently with antivirals active against orthopoxvirusesAdverse Effects
Very common (>10%):- Injection site reactions (pain, redness, swelling, induration)
- Fatigue
- Headache
- Myalgia
- Nausea
- Chills
- Fever
- Pruritus at injection site
- Myopericarditis (<0.1%)
- Hypersensitivity reactions (<0.1%)
Monitoring Parameters
- Local injection site reactions for 1-2 weeks post-vaccination
- Systemic symptoms (fever, fatigue, myalgia) for several days post-vaccination
- Signs of hypersensitivity reactions immediately post-vaccination
- Cardiac symptoms (chest pain, palpitations) for several weeks post-vaccination
- Vaccine effectiveness through antibody titers in immunocompromised patients
Patient Education
- Expect local reactions (redness, swelling, pain) at injection site that typically resolve within several days
- Systemic symptoms (headache, fatigue, muscle pain) are common and usually self-limited
- Use cool compresses and analgesics for symptom management if needed
- Seek immediate medical attention for signs of severe allergic reaction (hives, swelling, difficulty breathing)
- Report chest pain, palpitations, or shortness of breath to healthcare provider
- Complete both doses for optimal protection
- Continue protective measures until full immunity develops (2 weeks after second dose)
- Inform healthcare providers of vaccination history
References
1. FDA. Jynneos prescribing information. September 2019. 2. Petersen BW, et al. Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses - Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015. MMWR Morb Mortal Wkly Rep. 2016;65(10):257-262. 3. Rao AK, et al. Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(22):734-742. 4. Frey SE, et al. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects. Vaccine. 2015;33(48):5225-5234. 5. CDC. Monkeypox and Smallpox Vaccine Guidance. https://www.cdc.gov/poxvirus/monkeypox/clinicians/smallpox-vaccine.html