Smallpox And Mpox Vaccine, Live, Non-Replicating

Introduction Overview

Generic Name

smallpox and Mpox vaccine, live, non-replicating

Brand Name

Jynneos

Dosage Form

injectable suspension for subcutaneous use

Drug Class

Viral vaccines

Pharmacokinetics

Absorption:
Jynneos vaccine is administered via subcutaneous injection, which allows for direct introduction of the live, non-replicating Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) virus into the subcutaneous tissue. Upon injection, the vaccine antigen is absorbed primarily through the lymphatic system where it is taken up by antigen-presenting cells such as dendritic cells. These cells then migrate to regional lymph nodes where they initiate the adaptive immune response. The absorption kinetics are influenced by the site of injection, with the upper arm typically preferred for optimal immune stimulation. Intradermal administration, under Emergency Use Authorization, involves the injection of a smaller volume into the dermis layer, which is rich in antigen-presenting cells, potentially enhancing immune response despite lower doses.

Distribution:
Since Jynneos contains a live, attenuated but non-replicating virus, it does not disseminate widely beyond the injection site and regional lymph nodes. The vaccine virus is designed to elicit a local and systemic immune response without establishing productive infection or viremia. Clinical studies and post-marketing pharmacokinetic assessments have demonstrated that the MVA-BN virus remains localized and is not detected in blood or distant tissues in significant amounts. This limited biodistribution profile contributes to its improved safety profile compared to replicating smallpox vaccines.

Metabolism:
The MVA-BN viral particles in Jynneos are metabolized primarily through the host’s cellular processing pathways upon antigen exposure. The non-replicating virus cannot replicate within host cells but is processed via the endosomal and proteasomal pathways to present viral antigens on major histocompatibility complexes (MHC) to activate T-cell mediated immunity. Metabolic clearance involves enzymatic degradation of viral proteins and nucleic acid components, as well as immune-mediated clearance. Exogenous metabolic pathways for vaccine constituents such as stabilizers and preservatives follow typical processes for proteins and small molecules.

Elimination:
Elimination of the vaccine components follows a combination of cellular degradation and immune system clearance mechanisms. The live, non-replicating virus is cleared by immune cells once it has presented antigen, leading to degradation of viral particles and proteins. The excipients such as Tris, sodium chloride, dextran, and sucrose are eliminated via renal and metabolic pathways consistent with their chemical nature. The non-replicating viral platform significantly reduces risks associated with prolonged viral shedding or dissemination, contributing to the vaccine’s safety and tolerability profile.

Dosage Forms

Available Dosage Forms:
- Injectable suspension for subcutaneous use.
- Two formulations:
- Liquid-frozen, single-vial presentation requiring storage at -25°C to -15°C (-13°F to +5°F).
- Freeze-dried (lyophilized), two-vial presentation (lyophilized antigen and diluent) stored refrigerated at +2°C to +8°C (+36°F to +46°F).

Dosages for Adults and Adolescents:
- Standard subcutaneous dose: Two doses of 0.5 mL each administered 4 weeks apart.
- Emergency Use Authorization alternative intradermal dosing: Two doses of 0.1 mL each administered 4 weeks apart, to extend vaccine supply during public health emergencies.

Specific Patient Populations:
- Adults aged 18 years and older at high risk for smallpox or Mpox infection.
- Pediatric/adolescent patients younger than 18 years for Mpox prevention, authorized under EUA, receiving the same dosing schedule as adults (2 doses of 0.5 mL subcutaneously, 4 weeks apart).
- Immunocompromised individuals receive the vaccine with caution, understanding potential for diminished immune response.
- Pregnant and breastfeeding patients should discuss vaccination benefits and risks with their healthcare provider.

Storage and Handling:
- Liquid-frozen single vial: Maintain frozen prior to use; once thawed, can be refrigerated for up to 4 weeks but not refrozen.
- Lyophilized two-vial presentation: Antigen component stored refrigerated, diluent stored at room temp or refrigerated.
- After reconstitution, the vaccine should be used immediately or stored refrigerated for up to 12 hours, avoiding light exposure, and not refrozen.

Mechanism Of Action

Jynneos vaccine utilizes a live, non-replicating virus platform known as Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), a highly attenuated strain of vaccinia virus. This engineered virus is incapable of replication in human cells but retains the ability to express viral antigens, effectively simulating a natural infection to stimulate a robust immune response while ensuring an improved safety profile compared to replicating vaccinia vaccines.

Once administered via subcutaneous or intradermal injection, the MVA-BN virus infects antigen-presenting cells, including dendritic cells and macrophages, at the injection site. These cells process and present viral antigens via MHC class I and II molecules, activating both CD8+ cytotoxic T lymphocytes and CD4+ helper T cells. This activation promotes the development of cellular immunity essential for identifying and eliminating orthopoxvirus-infected cells, including smallpox and Mpox viruses.

Additionally, the vaccine induces humoral immunity by stimulating B cells to produce neutralizing antibodies targeting vaccinia virus antigens. These antibodies cross-react with related orthopoxviruses, providing protective immunity against smallpox and Mpox infection. The combination of cellular and humoral immune responses ensures comprehensive protection.

Compared to traditional smallpox vaccines like ACAM2000, which use replicating vaccinia virus, Jynneos’s non-replicating MVA-BN vector avoids systemic viral dissemination, reducing the risk of adverse events such as myocarditis. Clinical trials have validated that Jynneos elicits an effective immunogenic response with significantly lower incidence of serious complications, advancing it as a safer alternative for high-risk populations. Ongoing research continues to explore its efficacy in diverse cohorts and emergency use scenarios.

Pharmacological Actions

Induces active immunity against smallpox and Mpox viruses by stimulating both humoral and cellular immune responses.
Utilizes a live, non-replicating Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) viral vector to present orthopoxvirus antigens.
Elicits production of neutralizing antibodies that cross-react with orthopoxviruses, conferring protection.
Activates antigen-presenting cells leading to T-cell mediated cytotoxic responses essential for virus clearance.
Non-replicating nature reduces risk of vaccine-related adverse events common to replicating vaccinia virus vaccines.
Demonstrates immunogenicity in adult and pediatric populations with a favorable safety profile.
Stimulates memory B-cell and T-cell populations to provide long-lasting immunity.
Can be administered via subcutaneous or intradermal routes with proven immunological efficacy.
Does not cause systemic viral infection or spread, minimizing complications in immunocompromised patients.
Functions as a prophylactic immunization against potential smallpox bioterrorism exposure and emerging Mpox outbreaks.

Therapeutic Or Clinical Uses

Prevention of smallpox infection in adults determined to be at high risk of exposure.
Prevention of Mpox (monkeypox) disease in adults and adolescents 18 years and older at high risk of infection.
Emergency Use Authorization for use in pediatric and adolescent populations under 18 years at high risk of Mpox infection.
Prophylactic vaccination for laboratory personnel and healthcare workers potentially exposed to orthopoxviruses.
Recommended for use in public health emergency settings involving potential bioterrorism or infectious disease outbreaks involving orthopoxviruses.
Alternative to replicating vaccinia vaccines for individuals contraindicated for traditional live vaccinia vaccines.
Pre-exposure immunization for populations with occupational or epidemiological risk of smallpox or Mpox.
Immunization strategy component included in national stockpiles for biodefense preparedness.
Considered for administration in immunocompromised individuals with assessment of risk-benefit ratio due to non-replicating virus properties.
Used to support control of Mpox outbreaks in conjunction with public health measures.

Side Or Adverse Effects

Pain, redness, swelling, and induration at the injection site are the most common local reactions.
Itching at the injection site may occur following vaccination.
Muscle pain (myalgia) reported in vaccinated individuals.
Headache is a frequently observed systemic side effect.
Fatigue or tiredness commonly occurs post-vaccination.
Nausea may occur transiently after receiving the vaccine.
Chills have been reported in some vaccine recipients.
Individuals previously vaccinated may experience fewer systemic symptoms but similar local injection site reactions.
Rare severe allergic reactions (anaphylaxis) can occur; immediate medical treatment is essential.
No documented vaccine virus dissemination or vaccine-related severe adverse events typical of replicating vaccinia virus vaccines.
Post-vaccination lymphadenopathy may rarely be observed due to immune activation.
Injection site induration may persist for several days before resolution.
Side effects are generally mild to moderate and self-limiting in duration.
Adverse effect profiles are consistent across adult and authorized pediatric populations under EUA.
Immunocompromised patients may have a diminished immune response without increased adverse events.

Precautions

Do not administer to individuals with a known life-threatening allergy to any component of the vaccine or prior smallpox or Mpox vaccine.
Use caution in persons with immunocompromising conditions or those receiving immunosuppressive therapies as immune response may be reduced.
Inform healthcare providers about any current medications including steroids, chemotherapy agents, or biological immunomodulators prior to vaccination.
Pregnant and breastfeeding women should discuss the risks and benefits of vaccination with their healthcare professional.
Patients with a history of severe allergic reactions to vaccines should be closely monitored after administration.
Avoid administration in patients with active, untreated skin conditions at the injection site.
Follow local and federal guidelines regarding vaccination schedules and contraindications specific to vulnerable populations.
Ensure emergency medical treatment is readily available during and post administration for management of rare anaphylactic reactions.
Do not freeze the vaccine after thawing or after reconstitution for two-vial presentations to maintain vaccine efficacy.
Instruct patients to report any unexpected or persistently severe side effects following vaccination.
Vaccination may not provide complete protection—continue to practice other disease prevention measures.
Consult healthcare professionals if prior vaccine reactions or underlying health issues exist.
Consider timing of concomitant vaccinations or immunosuppressive therapies to optimize immune response.
Monitor for signs of infection or adverse reactions especially in individuals receiving multiple immunomodulating treatments.
Adhere to storage and handling recommendations to preserve vaccine integrity.

Warnings

Jynneos should only be used as directed under professional healthcare supervision.
Serious allergic reactions, including anaphylaxis, have been reported; immediate emergency medical care is required if symptoms such as hives, difficulty breathing, or facial swelling occur.
Immunocompromised persons may have reduced protective response to the vaccine, and additional precautions should be considered.
Vaccination may not fully protect all recipients from smallpox or Mpox disease.
Do not administer to individuals with known severe allergies to any vaccine components or prior smallpox/Mpox vaccines.
Vaccine effectiveness has not been established in pregnant or breastfeeding populations; use only if clearly needed.
Avoid use in patients with active eczema or atopic dermatitis due to potential increased risk of adverse skin reactions.
Ensure vial handling recommendations to avoid loss of potency, especially in freeze-dried and frozen formulations.
Emergency Use Authorization dosing (intradermal) is reserved for public health emergencies and should follow specific regulatory guidance.
Monitor vaccine recipients for immediate adverse reactions in clinical settings equipped to manage emergencies.
Delayed hypersensitivity or local reactions could occur; patients should be informed of symptoms requiring medical evaluation.
Not recommended for use outside authorized indications and populations without appropriate clinical oversight.
Healthcare providers should report adverse events to appropriate vaccine safety monitoring systems promptly.
Vaccine must not be reused once thawed or reconstituted beyond recommended storage times.
The safety and efficacy of Jynneos in patients with severe immunodeficiency remain under ongoing investigation.

Contraindication

History of life-threatening allergic reaction to Jynneos or any of its components.
Previous severe allergic reaction to any smallpox or Mpox vaccine.
Known hypersensitivity to vaccine excipients, including Modified Vaccinia Ankara virus or stabilizers.
Patients with active severe eczema or other exfoliative skin conditions should avoid vaccination due to risk of serious adverse skin reactions.
Contraindicated in individuals with certain severe immunodeficiency disorders where live vaccines pose undue risk.
Individuals who have had previous adverse reactions to vaccinia-based vaccines that preclude re-vaccination.
Do not administer outside of approved dosage and indications as established by regulatory authorities.
Persons lacking clinical assessment for risk of smallpox or Mpox exposure without an indication for vaccination.
Contraindication applies to vaccine formulations as labeled unless alternate dosing approved under EUA.
Known allergy to gentamicin, ciprofloxacin, or other trace antibiotics in vaccine preparation may require evaluation.
Patients who are febrile or acutely ill at time of intended vaccination should defer until recovery.
Pregnancy is generally considered a precaution; however, vaccination is contraindicated only when potential risks outweigh benefits.
Individuals unable to tolerate subcutaneous or intradermal injections due to hypersensitivity or severe skin conditions.
Contraindicated in case of unauthorized or improper vaccine storage leading to loss of potency or contamination.
Individuals with a history of anaphylaxis to any vaccine component must not receive Jynneos.

Drug Interactions

Concomitant administration with other vaccines may interfere with immune response; inform healthcare provider of recent vaccinations.
Immunosuppressive drugs including corticosteroids, chemotherapy agents, and radiation therapy may diminish vaccine immunogenicity.
Medications used to treat autoimmune diseases, such as biologics and disease-modifying agents, may affect vaccine efficacy.
Drugs used to prevent organ transplant rejection (e.g., calcineurin inhibitors) can reduce immune response elicited by the vaccine.
No direct pharmacokinetic drug interactions reported due to the live, non-replicating viral platform.
Concomitant use with immunomodulatory supplements or herbal products should be reported to ensure clinical monitoring.
Vaccination timing may need adjustment around treatments that cause temporary lymphopenia or leukopenia.
Live vaccines can sometimes interact with immune system modifiers; close monitoring is indicated.
Co-administration with systemic corticosteroids at immunosuppressive doses should be avoided or deferred if possible.
Interactions with antiviral agents targeting orthopoxviruses are not well characterized; clinical judgment advised.
Use caution when scheduling vaccination with other biologic agents or immune checkpoint inhibitors.
Patients on antiretroviral therapy for HIV should be assessed to ensure adequate immune status before vaccination.
Potential interactions with antibiotics trace amounts (gentamicin, ciprofloxacin) are unlikely but may require allergy assessment.
Inform the provider of all prescription, over-the-counter, and herbal medications to avoid unforeseen immunological interactions.
Drug interaction data continues to evolve; consult latest clinical guidelines and product monographs.

Preparations Of The Drug

One-vial liquid-frozen presentation containing ready-to-use MVA-BN vaccine in a single vial with a yellow cap; does not require reconstitution.
Two-vial lyophilized presentation comprising: - Lyophilized Antigen Component (yellow cap vial) requiring reconstitution. - Diluent Component (blue cap vial) used to reconstitute antigen prior to administration.
Dose strength: each 0.5 mL dose contains 0.5 × 10^8 to 3.95 × 10^8 infectious units of MVA-BN live virus.
Excipients include Tris (0.61 mg), Sodium chloride (4.09 mg), Dextran 40 (9.45 mg), Sucrose (22.5 mg), and Potassium L-glutamate monohydrate (0.054 mg) post-reconstitution.
May contain trace amounts of host-cell DNA (≤20 mcg), protein (≤500 mcg), benzonase (≤0.0025 mcg), gentamicin (≤0.400 mcg), and ciprofloxacin (≤0.005 mcg).
Storage requirements: - Liquid-frozen: stored at -25°C to -15°C, protected from light, no refreezing after thawing. - Lyophilized antigen: refrigerated at +2°C to +8°C, protected from light. - Diluent: stored at room temperature or refrigerated. - Reconstituted vaccine: used immediately or refrigerated for up to 12 hours, protected from light.
Formulated for subcutaneous injection, with EUA permitting intradermal administration at reduced volume for dose-sparing.
Manufactured by Bavarian Nordic A/S located in Hellerup, Denmark.
Vials are single-dose, intended for single use only with disposal of unused portions per standard biomedical waste procedures.
Packaging designed for protection during storage and transport, complying with cold chain logistics.
Quality control and potency testing ensure safe and consistent vaccine preparations for clinical use.
The vaccine is supplied for administration in healthcare settings including clinics, pharmacies, and hospitals.
Instructions emphasize proper reconstitution technique for two-vial presentations to ensure vaccine efficacy.
Labeling includes detailed usage instructions, expiration dates, and lot identification for pharmacovigilance.