JYNNEOS Vaccine

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Interim Guidance

CDC recommends that vaccination with JYNNEOS can be considered for persons determined to be at high risk for infection to prevent mpox.

Vaccination Schedule

JYNNEOS vaccine is licensed as a series of two doses administered 28 days (4 weeks) apart.

The standard regimen involves a subcutaneous (Subcut) route of administration with an injection volume of 0.5mL. The standard regimen is the FDA-approved dosing regimen. Since August 9, 2022, the standard regimen has also been authorized for people aged <18 years under an Emergency Use Authorization.

An alternative regimen may be used for people age ≥18 years under an Emergency Use Authorization which was issued on August 9, 2022. The authorized alternative regimen involves an intradermal (ID) route of administration with an injection volume of 0.1mL. The alternative regimen, when feasible, is preferred because this could increase the number of available JYNNEOS vaccine doses by up to five-fold. Results from a clinical study showed that the lower intradermal dose was immunologically non-inferior to the standard subcutaneous dose [Frey SE et al., Vaccine, 2015; 33(39):5225-5234]. Recently published studies show similar vaccine effectiveness for vaccines administered subcutaneously or intradermally.

Either the standard (0.5mL subcutaneous) or the alternative (0.1mL ID) regimen may be used. Providers may discuss with patients to determine which route of administration each patient prefers.

Table 2. Vaccination Schedule and Dosing Regimens for JYNNEOS Vaccine
JYNNEOS vaccine regimen Route of administration Injection volume Recommended number of doses Recommended interval between 1st and 2nd dose
Standard regimen¹
People age ≥18 years Subcut 0.5 mL 2 28 days (4 weeks)
People age <18 years² Subcut 0.5 mL 2 28 days (4 weeks)
Alternative regimen
People age ≥18 years ID 0.1 mL 2 28 days (4 weeks)

1People of any age who have a history of developing keloid scars are recommended to receive the standard regimen of JYNNEOS.

2Prior to administration in people younger than age 6 months, clinicians should first contact their jurisdictional health department (Jurisdictional Contacts). Jurisdictional health departments can facilitate consultation with CDC if needed.

Every year, unsafe injection practices by U.S. healthcare providers, such as syringe reuse and misuse of medications vials, causes outbreaks. It is the responsibility of every provider who prepares and administers injections, or supervises those that prepare and administer injections, to ensure that patients receive the correct medication and are not exposed to life-threatening infections. Providers should adhere to Standard Precautions and the principles of Safe Injection Practices, including the use of a sterile, single-use, disposable needle and syringe for each injection given, and prevention of contamination of injection equipment and medication.

See the following resources for further information, including on how to safely store, prepare, and administer vaccines:

For further instructions on use of JYNNEOS mpox vaccine, refer to the Provider Agreement for the HHS Mpox Vaccination Program.

Duration of Immunity

Peak immunity is expected to be reached 14 days after the second dose of JYNNEOS vaccine. The duration of immunity after one or two doses of JYNNEOS is currently unknown.

Dosing Intervals

Recommended interval: The second dose of JYNNEOS vaccine should be given 28 (4 weeks) days after the first dose. Based on available clinical study data [13 MB, 93 pages], the second dose may be given up to 7 days later than the minimum interval of 28 days  (i.e., up to 35 days after the first dose).

Minimum interval: The vaccine manufacturer advises against giving the second dose before the minimum interval of 28 days. However, based on ACIP’s general best practices, a dose may be administered up to 4 days before the minimum interval of 28 days (known as the “grace period,” which would be a minimum of 24 days after the first dose). Vaccine doses should not be administered before the minimum interval. Nevertheless, if the second dose is inadvertently administered before the minimum interval, the dose may not need to be repeated. Please refer to “Table 7. Vaccine Administration Errors and Deviations.

Maximum interval: If the second dose is not administered during the recommended interval, it should be administered as soon as possible based on ACIP’s general best practices. There is no need to restart or add doses to the series if there is an extended interval between doses.

Evidence Quality

JYNNEOS is approved for the prevention of mpox disease in individuals 18 years of age and older at high risk for mpox infection. Licensure was supported by animal studies as well as clinical studies demonstrating a comparable immune response to ACAM2000 (Rao AK et al, MMWR, 2022; 71(22):734-742). No immune correlate of protection (i.e., minimum threshold level of antibodies needed to prevent symptoms) has been established. One peer-reviewed study of 524 randomized subjects found that immunogenicity was non-inferior following the alternative regimen (intradermal injection) versus the standard regimen (subcutaneous injection) (Frey SE et al, Vaccine, 2015; 33(39):5225-5234). This study supported the authorization of the alternative dosing regimen with intradermal injection for people 18 years of age and older.

The evidence to support the authorized use of JYNNEOS by the subcutaneous route to individuals younger than 18 years of age is based on the data which supported the approved use of JYNNEOS and historical data on the use of smallpox vaccine in the pediatric population.

Immunogenicity of JYNNEOS has been studied among people with HIV infection (Overton ET et al, Open Forum Infect Dis, 2015 Apr; 2(2):ofv040). Studies of intradermal administration of influenza vaccines among people with HIV infection suggest similar immunogenicity compared with other routes of administration (Garg S et al, Clin Infect Dis. 2016; 62(3):383-391). No data are currently available on intradermal administration of JYNNEOS for people with severe immunosuppression (Altered Immunocompetence Guidelines for Immunizations from ACIP).

The risk for serious adverse events after either the standard regimen or the alternative regimen is expected to be low. Review of previous Vaccine Adverse Event Reporting System (VAERS) reports from influenza vaccine products that were administered intradermally identified no new or unexpected safety concerns, and injection-site reactions were the most commonly reported adverse events. The alternative regimen is likely to be acceptable and feasible.

No data are available on cost-effectiveness, values, or health equity. The level of certainty for the evidence for public health benefits is considered low, but desirable consequences probably outweigh undesirable consequences in most settings. The balance of consequences favors the intervention in the context of a current public health emergency. These interim clinical considerations may change as additional evidence is considered.

Storage and Administration

Predrawing JYNNEOS Vaccine

Predrawing vaccines can result in waste if more are drawn up than needed. In addition, once vaccines are drawn into syringes, it is difficult to tell them apart, which can lead to administration errors. However, there may be rare instances when the only option is to predraw JYNNEOS vaccine. If vaccines must be predrawn:

  • Predrawn vaccine must be labeled with vaccine name, lot number, date and time prepared, and preparer’s initials, and MUST BE refrigerated.
  • Predrawn syringes must be stored at the manufacturer-recommended [3 MB, 70 pages] refrigerated temperatures throughout the clinic day.
  • A separate clean administration station for each vaccine type should be set up to prevent medication errors.
  • Vaccines should be drawn up into syringes only after arriving at the clinic site, or mass vaccination event. Drawing up doses days or even hours before administering them is not a best practice because general-use syringes are not designed for storage.
  • Each person administering vaccines should draw up no more than 10 doses at one time.
  • Patient flow should be monitored to avoid drawing up unnecessary doses.
  • If a predrawn vaccine is not used within 8 hours of being drawn, the dose should be discarded.
  • Predrawn vaccine should never be transferred back into a vial for storage.

Intradermal (ID)

Intradermal administration involves injecting the vaccine superficially between the epidermis and the hypodermis layers of the skin, typically of the volar aspect (inner side) of the forearm. If the volar aspect of the forearm is not an option (e.g., strong patient preference),  intradermal administration of vaccine may be performed at the upper back below the scapula or at the deltoid. Producing a noticeable pale elevation of the skin (wheal) with the intradermal injection is desirable but not required. Please refer to related resources, including intradermal administration teaching tools and the JYNNEOS Preparation & Administration Summary (Alternative Regimen) for further details on intradermal vaccine administration.

A person who presents for their second JYNNEOS vaccine dose who is still experiencing erythema or induration at the site of intradermal administration of the first vaccine dose (e.g., the forearm) should have the second dose administered intradermally in the contralateral forearm or if that is not an option, in the upper back below the scapula, or at the deltoid.

Video on Administering JYNNEOS Intradermally

This video demonstrates how to administer an intradermal vaccine.
VIDEO

How to Administer Intradermal Vaccine in Forearm, Deltoid, and Scapula

Video Length: 00:02:49

Watch Video

Images on Administering JYNNEOS Intradermally

How to administer a Jynneos vaccine intradermally
Step 1: Locate and clean a site for injection in the inner (volar) surface of the forearm.
How to administer a Jynneos vaccine intradermally
Step 2a: While pulling the skin taut, position the needle with the bevel facing up and insert the needle at a 5- to 15-degree angle into the dermis.
How to administer a Jynneos vaccine intradermally
Step 2b: While pulling the skin taut, position the needle with the bevel facing up and insert the needle at a 5- to 15-degree angle into the dermis.
How to administer a Jynneos vaccine intradermally
Step 3: Slowly inject 0.1 mL intradermally. This should produce a noticeable pale elevation of the skin (wheal).
How to administer a Jynneos vaccine intradermally
Step 4: Observe patients for 15 minutes after vaccination or 30 minutes if they have a history of anaphylaxis to gentamicin, ciprofloxacin, chicken or egg protein.
Example of intradermal administration at the deltoid.

Example of locating and cleaning the site for intradermal administration at the deltoid.

Example of intradermal administration at the deltoid.

Example of intradermal administration at the deltoid.

Example of intradermal administration at the upper back below the scapula.

Example of locating and cleaning the site for intradermal administration at the upper back below the scapula.

Example of intradermal administration at the upper back below the scapula.

Example of intradermal administration at the upper back below the scapula.

Subcutaneous (Subcut)

Subcutaneous administration involves injecting the vaccine into the fatty tissue, typically over the triceps in people aged 12 months and older, or in the anterolateral thigh for people younger than age 12 months. CDC offers a short training video about subcutaneous vaccine administration. Please refer to the JYNNEOS Preparation & Administration Summary (Standard Regimen) for further details on subcutaneous vaccine administration.

Interchangeability of Dosing Regimens

When necessary in eligible individuals, the dosing regimens are interchangeable. For example, a person aged 18 years or older who received one JYNNEOS vaccine dose with the standard subcutaneous regimen may receive a second dose with the alternative intradermal regimen at the recommended interval (i.e., 28 days) to complete the vaccination series. Another example is a person who received the first dose intradermally, had a robust local reaction, and refuses a second dose unless given subcutaneously. In this situation, that second dose can be given subcutaneously.

Coadministration of JYNNEOS Vaccine with Other Vaccines

Currently, there are no data on administering JYNNEOS vaccine at the same time as other vaccines. Because JYNNEOS is based on a live, attenuated non-replicating orthopoxvirus, JYNNEOS typically may be administered without regard to timing of most other vaccines. This includes simultaneous administration of JYNNEOS and other vaccines, including influenza vaccine, on the same day, but at different anatomic sites if possible.

However, there are additional considerations if administering a COVID-19 vaccine. (Interim Clinical Considerations for Use of COVID-19 Vaccines)

  • There is no required minimum interval between receiving any COVID-19 vaccine and an orthopoxvirus vaccine, either ACAM2000 or JYNNEOS vaccine (e.g., for mpox prevention), regardless of which vaccine is administered first.
  • Use of JYNNEOS vaccine should be prioritized over ACAM2000 when co-administering a COVID-19 vaccine and an orthopoxvirus vaccine.
  • People, particularly adolescent and young adult males, who are recommended to receive both vaccines might consider waiting 4 weeks between vaccines. This is because of the observed risk for myocarditis and pericarditis after receipt of ACAM2000 orthopoxvirus vaccine and COVID-19 vaccines and the hypothetical risk for myocarditis and pericarditis after JYNNEOS vaccine. However, if a patient’s risk for mpox or severe disease due to COVID-19 is increased, administration of mpox and COVID-19 vaccines should not be delayed.

Best practices for multiple injections include:

  • Label each syringe with the name and the dosage (amount) of the vaccine, lot number, initials of the preparer, and exact beyond-use time, if applicable.
  • Administer each injection in a different injection site; separate injection sites by 1 inch or more, if possible.
  • Administer the JYNNEOS vaccine and vaccines that may be more likely to cause a local reaction in different limbs, if possible.

Review ACIP’s general best practices and Epidemiology and Prevention of Vaccine-Preventable Diseases (CDC Pink Book) for further information.

Coadministration of JYNNEOS vaccine with the tuberculin skin test

Currently, there are no data on administering JYNNEOS vaccine at the same time as the tuberculin skin test (TST). While JYNNEOS is a live virus vaccine, it is non-replicating and its effect on the response to the TST may not be the same as for live, replicating virus vaccines such as measles-mumps-rubella (MMR).

If a delay in the TST would cause substantial burden (e.g., preventing a person from working because of pre-employment screening policies) then the TST should not be delayed. If delays in the TST will not cause substantial burden, a delay of at least 4 weeks after JYNNEOS vaccination is preferred.

The TST can be performed at the same time as JYNNEOS vaccination and any sequence of vaccination and the TST may be used. If the JYNNEOS vaccine and the TST are administered on the same day, the vaccine and the TST should be administered on different forearms, one on the left and one on the right.  The location of each injection site should be recorded in order to read the TST result from the correct forearm. If the JYNNEOS vaccine and the TST are administered on the same forearm, the sites of injection should be separated by 8–10 centimeters (that is, 3–4 inches) along the length of the forearm, to reduce likelihood of overlap of any reactions from the two injections, and the location of each injection site and the antigen should be recorded.

For patients who have symptoms or signs of active tuberculosis (TB), all tests and examinations for TB diagnosis should be pursued without delay, regardless of JYNNEOS vaccination.

Patient Counseling

Pre-vaccination Counseling

Recipients should be informed of the risks and benefits of JYNNEOS prior to vaccination. Healthcare providers should determine the medical history of recipients to appropriately decide whether to administer the vaccine subcutaneously or intradermally. Recipients should be counseled about possible side effects from vaccination and be provided with a JYNNEOS vaccine information statement (VIS) or FDA JYNNEOS EUA Fact Sheet, as applicable.

Side effects after vaccination can vary from person to person. Before vaccination, each recipient should be counselled on the possibility of experiencing the following side effects:

Local Side Effects:

  • Erythema
  • Pain
  • Edema
  • Pruritis
  • Hyperpigmentation
  • Induration

Systemic Side Effects:

  • Fatigue
  • Headache
  • Myalgias
  • Nausea
  • Chills
  • Fever

Local side effects may be more severe with intradermal administration compared with subcutaneous administration. Side effects may appear soon after vaccination, and some local reactions, such as hyperpigmentation, may persist for several weeks or months. One study noted mild injection site skin discoloration lasting greater than six months for some individuals receiving intradermal administration. Recipients should be counseled that such long-lasting local reactions are expected and may be part of the normal immune response to vaccination. Patients should also be counseled that these side effects are usually self-limiting and will generally resolve over time. While the presence of local or systemic side effects may indicate the development of a robust immune response, the absence of such reactions should not be construed as not mounting adequate immune protection, as the severity and duration of side effects can vary from person to person.

Post-vaccination Counseling

Local and systemic reactions experienced after vaccination may be managed conservatively. Evidence does not support the use of antipyretics before or at the time of vaccination. However, they can be used for the treatment of fever and local discomfort that might occur following vaccination. Topical emollients, cold compresses, and oral antihistamines may be used to treat local side effects as needed. Do NOT apply topical corticosteroids or antihistamines to local reactions. Weeping or open wounds should be covered by a sterile gauze or bandage. If symptoms persist 28 days after receiving the first dose, the second dose should be placed intradermally in the contralateral forearm.

Given the unknown effectiveness of vaccination in this outbreak, people who are vaccinated should continue to take steps to protect themselves from infection by avoiding close, skin-to-skin contact, including intimate contact, with someone who has mpox.

Clinical studies have not detected an increased risk for myopericarditis in recipients of JYNNEOS. However, people with underlying heart disease or three or more major cardiac risk factors should be counseled about the theoretical risk for myopericarditis following vaccination with JYNNEOS, given the uncertain etiology of myopericarditis associated with replication-competent smallpox vaccines such as ACAM2000.

Safety

Contraindications and precautions

People presenting with minor illnesses, such as a cold, may be vaccinated. People who are moderately or severely ill should usually wait until they have recovered to their baseline state of health before vaccination. A person offered JYNNEOS vaccine due to an exposure to mpox virus or disease should be vaccinated regardless of pregnancy, breastfeeding, or weakened immune system.

Vaccine providers, particularly when vaccinating adolescents, should consider observing patients (with patients seated or lying down) for 15 minutes after vaccination to decrease the risk for injury should they faint. If syncope develops, patients should be observed until the symptoms resolve.

CDC considers vaccination with JYNNEOS to be either contraindicated (not recommended) or a precaution in the following situations.

Table 3. Contraindications and Precautions for Use of JYNNEOS Vaccine

Medical condition or history

Medical condition or history

Medical condition or history

Interim guidance

Interim guidance

Interim guidance

Suggested action(s)

Suggested action(s)

Suggested action(s)

History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of JYNNEOS

Medical condition or history

History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of JYNNEOS

Contraindication

Interim guidance

Contraindication

Do not vaccinate. Referral to an allergist-immunologist should be considered to assess the risks versus benefits of administering a dose.

Suggested action(s)

Do not vaccinate. Referral to an allergist-immunologist should be considered to assess the risks versus benefits of administering a dose.

History of severe allergic reaction (e.g., anaphylaxis) following receipt of gentamicin or ciprofloxacin1

Medical condition or history

History of severe allergic reaction (e.g., anaphylaxis) following receipt of gentamicin or ciprofloxacin1

Precaution

Interim guidance

Precaution

Discuss risks and benefits with potential recipients. Patients may be vaccinated with a 30-minute observation period following administration.

Alternatively, vaccination may be delayed until an allergist-immunologist is consulted, but the impact of delaying vaccination should be considered.

Suggested action(s)

Discuss risks and benefits with potential recipients. Patients may be vaccinated with a 30-minute observation period following administration.

Alternatively, vaccination may be delayed until an allergist-immunologist is consulted, but the impact of delaying vaccination should be considered.

History of severe allergic reaction (e.g., anaphylaxis) to chicken or egg protein AND currently avoiding exposure to all chicken or egg products1

Medical condition or history

History of severe allergic reaction (e.g., anaphylaxis) to chicken or egg protein AND currently avoiding exposure to all chicken or egg products1

Precaution

Interim guidance

Precaution

Discuss risks and benefits with potential recipients. Patient may be vaccinated with a 30-minute observation period following administration.

Alternatively, vaccination may be delayed until an allergist-immunologist is consulted, but the impact of delaying vaccination should be considered.

Suggested action(s)

Discuss risks and benefits with potential recipients. Patient may be vaccinated with a 30-minute observation period following administration.

Alternatively, vaccination may be delayed until an allergist-immunologist is consulted, but the impact of delaying vaccination should be considered.

Moderate or severe acute illness, with or without fever

Medical condition or history

Moderate or severe acute illness, with or without fever

Precaution

Interim guidance

Precaution

Consider deferring vaccination until the acute illness has improved.

Suggested action(s)

Consider deferring vaccination until the acute illness has improved.

1 JYNNEOS vaccine contains small amounts of gentamicin and ciprofloxacin and is produced using chicken embryo fibroblast cells.

Vaccine providers should be familiar with identifying immediate-type allergic reactions, including anaphylaxis, and be competent in treating these events at the time of vaccine administration. Providers should also have a plan in place to contact emergency medical services immediately in the event of a severe acute vaccine reaction. (ACIP Adverse Reactions Guidelines for Immunization)

CDC’s Clinical Immunization Safety Assessment (CISA) Project is available to provide consultation to U.S. healthcare providers and health departments about complex mpox vaccine safety questions for their patients. See Clinical Immunization Safety Assessment (CISA) Project.

Reporting of Adverse Events

The Vaccine Adverse Event Reporting System (VAERS) is the nation’s early warning system that monitors the safety of vaccines after they are authorized or licensed for use by the U.S. Food and Drug Administration. VAERS accepts and analyzes reports of adverse events following vaccination.

The vaccination provider must report all serious adverse events following administration of JYNNEOS or ACAM2000 vaccine and vaccine administration errors to VAERS.

Per the Emergency Use Authorization (JYNNEOS), the Expanded Access Investigational New Drug protocol (ACAM2000), and the HHS Mpox Vaccination Program Provider Agreement, the vaccination provider is responsible for mandatory reporting of the following listed events after JYNNEOS or ACAM2000 vaccination to VAERS:

  • Vaccine administration errors, whether or not associated with an adverse event
  • Serious* adverse events (irrespective of attribution to vaccination)
  • Cases of cardiac events, including myocarditis and pericarditis
  • Cases of thromboembolic events and neurovascular events

*Serious adverse events are defined as:

  • Death
  • A life-threatening adverse event
  • Inpatient hospitalization or prolongation of existing hospitalization
  • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
  • A congenital anomaly/birth defect
  • An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent one of the outcomes listed above

Providers are encouraged to also report to VAERS any additional clinically significant adverse events following vaccination, even if they are not sure if vaccination caused the event.

On August 9, 2022, FDA issued an EUA for JYNNEOS mpox vaccine. It authorizes the vaccine to be administered in one of two ways:

  1. Intradermally, between the layers of the skin, preferably on the inner aspect of the forearm, or
  2. Subcutaneously, under the skin, in the upper arm above the elbow.

These are considered routes of vaccination. When submitting a VAERS report, ensure that you document the Route in Section 17 of the VAERS form, by choosing “intradermal” or “subcutaneous” from the selection menu.

For information on how to submit a report to VAERS, visit VAERS—Report an Adverse Event (hhs.gov) or call 1-800-822-7967.