Monkeypox in the U.S. (2023)

Interim Guidance

CDC recommends that vaccination with JYNNEOS can be considered for people determined to be at high risk for infection to prevent monkeypox disease.

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.

In the context of the current nationalPublic Health Emergency (PHE), analternative regimenmay 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).

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 18 years, 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, can cause 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 ofSafe 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:

• ACIP’sgeneral best practices andEpidemiology and Prevention of Vaccine-Preventable Diseases(CDC Pink Book)and
• CDC’sVaccine Administration Toolsand
• CDC’sOne and Only CampaignandFAQs regarding safe injection practiceslike preparation, administration, and handling of single-dose vials.

For further instructions on use of JYNNEOS monkeypox vaccine, refer to the Provider Agreement for the HHS Monkeypox 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 two doses of JYNNEOS is 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 monkeypox disease in individuals 18 years of age and older at high risk for monkeypox 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 versus the standard regimen (Frey SE et al, Vaccine, 2015; 33(39):5225-5234). This study supported the authorization of the alternative dosing regimen 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 Immunizationsfrom 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.

Administration

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 torelated resources, including intradermal administration teaching tools and the 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.

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. The manufacturer of JYNNEOS has agreed that it is acceptable to administer this vaccine in the subcutaneous tissue over the triceps area, even though the package insert for JYNNEOS states the site of administration is “deltoid.” CDC offers a short trainingvideo about subcutaneous vaccine administration. Please refer to the for further details on subcutaneous vaccine administration.

Interchangeability of Dosing Regimens

When necessary, 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. For example, a person who received only one dose of the standard regimen before the date of initial Emergency Use Authorization for the alternative regimen (August 9, 2022), may receive one dose with the alternative regimen to complete the series. Also, a person whose 18^thbirthday occurs between their first and second dose may complete the series with the alternative regimen.

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 other vaccines. This includes simultaneous administration of JYNNEOS and other vaccines 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)

• If an orthopoxvirus vaccine is offered for prophylaxis in the setting of an orthopoxvirus (e.g., monkeypox) outbreak, orthopoxvirus vaccination should not be delayed because of recent receipt of a Moderna, Novavax, or Pfizer-BioNTech COVID-19 vaccine; no minimum interval between COVID-19 vaccination with these vaccines and orthopoxvirus vaccination is necessary.
• People, particularly adolescent or young adult males, might consider waiting 4 weeks after orthopoxvirus vaccination (either JYNNEOS or ACAM2000) before receiving a Moderna, Novavax, or Pfizer-BioNTech COVID-19 vaccine, because of the observed risk for myocarditis and/or pericarditis after receipt of ACAM2000 orthopoxvirus vaccine and mRNA (i.e., Moderna and Pfizer-BioNTech) and Novavax COVID-19 vaccines and the unknown risk for myocarditis and/or pericarditis after JYNNEOS administration.

Best practicesfor 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 practicesandEpidemiology 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. 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 shouldnotbe 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 infectionby avoiding close, skin-to-skin contact, including intimate contact, with someone who has monkeypox.

Clinical studies have not detected an increased risk for myopericarditis in recipients of JYNNEOS. However, people with underlying heart disease orthree or more major cardiac risk factorsshould 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 monkeypox 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.

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 are available to provide consultation to U.S. healthcare providers and health departments about complex monkeypox vaccine safety questions for their patients. (Clinical Immunization Safety Assessment (CISA) Project).

Reporting of AdverseEvents

Vaccination providers are responsible for MANDATORY reporting of the following listed events following JYNNEOS vaccination to the Vaccine Adverse Event Reporting System (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 and neurovascular events

Reporting is encouraged for any clinically significant adverse event, even if it is uncertain whether the vaccine caused the event.

Information on how to submit a report to VAERS is available athttps://vaers.hhs.govor by calling 1-800-822-7967.