Vaccination Overview

Vaccines

Two vaccines may be used to prevent mpox:

• JYNNEOS^® vaccine is licensed to prevent smallpox and mpox and recommended by the Advisory Committee on Immunization Practices (ACIP) for certain people at risk for exposure to orthopoxvirus infections, including mpox. During the ongoing clade II mpox outbreak, JYNNEOS has been the dominant vaccine used in the U.S.
• ACAM2000^® vaccine is licensed to prevent smallpox and recommended by the ACIP for certain people at risk for exposure to orthopoxvirus infections. It has not been used in the ongoing clade II mpox outbreak that started in 2022.

JYNNEOS is a third-generation vaccine based on a live, attenuated orthopoxvirus, Modified Vaccinia Ankara (MVA). MVA is a live virus that does not replicate efficiently in humans. JYNNEOS is known internationally as Imvamune^® or Imvanex^®; it is manufactured by Bavarian Nordic. It is fully licensed in the U.S. for subcutaneous administration in individuals 18 years of age and older. As of April 1, 2024, JYNNEOS is commercially available in the U.S.

In addition, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) in August 2022 to allow JYNNEOS vaccine to be used:

• By intradermal injection for prevention of mpox disease in individuals 18 years of age and older determined to be at high risk for mpox, and
• By subcutaneous injection for prevention of mpox disease in individuals younger than 18 years of age determined to be at high risk for mpox.

ACAM2000 is a second-generation vaccine that contains a live vaccinia virus that replicates efficiently in humans. It is manufactured by Emergent Bio Solutions and is indicated for the prevention of smallpox. It has been made available for use against mpox in the clade II outbreak under an Expanded Access Investigational New Drug (EA-IND) protocol, which requires informed consent along with completing additional forms. Available evidence supporting the use of smallpox vaccine for mpox prevention is derived from experience with Dryvax^®, the vaccine used during smallpox eradication. Dryvax was a first-generation smallpox vaccine manufactured by Wyeth Laboratories. Routine use of this vaccine ended in the United States in 1972, and smallpox was declared eradicated globally in 1980 by the World Health Assembly. The license for Dryvax was withdrawn in 2008 and no supplies of this vaccine remain. Although the United States has a large supply of ACAM2000, this vaccine has more side effects and contraindications than JYNNEOS.

Recommendations for use of JYNNEOS vaccine

JYNNEOS vaccine is licensed as a series of two doses administered 28 days (4 weeks) apart. It was first made available through the U.S. Strategic National Stockpile during the start of the 2022 global mpox outbreak.

• Data collected since the 2022 outbreak have found that JYNNEOS is effective for the prevention of mpox.
• Two doses are more effective than one dose.
• Even when infections have occurred after 2 vaccine doses, they have typically been milder than the infections among people who are not vaccinated.

The Advisory Committee on Immunization Practices (ACIP) recommends the 2-dose JYNNEOS series to several populations and for different indications.

• For pre-exposure vaccination of people at risk for occupational exposure to orthopoxviruses (as an alternative to ACAM2000)
• For people aged 18 years and older at risk of mpox during an mpox outbreakA
  
  • CDC has determined that ongoing human-to-human transmission of clade I MPXV in Central and East Africa meets the criteria to be considered an outbreak and is issuing recommendations for vaccine use among travelers at increased risk of mpox exposure who are planning to travel to those specific countries.
  • Travelers to affected countries who anticipate the following activities should be offered vaccination with the 2-dose JYNNEOS series: sex with a new partner; sex at a commercial sex venue (e.g., sex club or bathhouse); sex in exchange for money, good, drugs, or other trade; or sex in association with a large public event (e.g., rave, party, or festival).
• For peopleB aged 18 years and older with the following risks:
  • 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: a new diagnosis of ≥1 sexually transmitted disease; more than one sex partner; sex at a commercial sex venue; or sex in association with a large public event in a geographic area where mpox transmission is occurring
  • Sexual partners of people with the risks described above
  • People who anticipate experiencing any of the above

Currently, CDC does not recommend routine immunization against mpox for the general public. JYNNEOS is not recommended as a routine vaccination for healthcare personnel unless sexual risk factors are present. Recommendations by the Advisory Committee on Immunization Practices (ACIP) are available for laboratory personnel and health care worker response teams who may be at risk for exposure to orthopoxviruses.

Why people who recovered from mpox do not need JYNNEOS vaccine

Recovery from MPXV infection (regardless of clade) likely confers protection from either clade of mpox. It is possible for individuals who have recovered from mpox to experience a reinfection, but reinfections are very rare. Unpublished data suggest that reinfection has occurred in less than 0.001% of people in the United States who previously had mpox. In these rare instances, the second infection was generally milder than the initial infection. Because of this, people who have recovered from mpox are not recommended to receive JYNNEOS vaccine doses at this time.

Why boosters aren’t currently recommended

Two doses of JYNNEOS vaccine can prevent MPXV infection and reduce the severity of mpox symptoms in people who have been vaccinated. Data from a multijurisdictional study in the U.S. demonstrated significant JYNNEOS vaccine effectiveness against mpox:

• 75% for one dose
• 86% after two doses

In addition, a recent study from the United Kingdom Health Security Agency estimated the effectiveness of the two-dose primary series of JYNNEOS at 80% for cases diagnosed in 2023.

No vaccine is 100% effective, but there are very few reports to CDC of mpox after vaccination with two doses of JYNNEOS vaccine. Data collected from May 2022-May 2024 during the clade IIb mpox outbreak in the United States show that infections after the two dose JYNNEOS vaccine series were rare. These infections:

• Were observed in <1% of people vaccinated with two doses of JYNNEOS vaccine (271 cases), which is consistent with the expected high degree of effectiveness after two doses
• Occurred at disparate time intervals after vaccination with no pattern that can be attributed to waning immunity
• Were associated with less severe infections when they occurred.

Why CDC does not recommend booster doses for the general population vaccinated during the ongoing clade IIb mpox outbreak.

Unpublished data from a CDC study in the Democratic Republic of the Congo that began in 2017 with 1,600 healthcare personnel receiving two doses of JYNNEOS demonstrated only one reported laboratory-confirmed infection in this region of high clade I mpox transmission. This study indicated that a booster dose five years after receiving the JYNNEOS primary series leads to a rapid and robust antibody response irrespective of circulating antibody levels at the time of booster dose. These results suggest that immunity does not wane for at least five years; a seven-year time point is currently being evaluated.

Serologic studies have shown antibody titers decrease a few months after vaccination. However, it is not known if a specific antibody titer is required to provide protection. Further, the levels of circulating titers are not the only marker of protection. Cell-mediated immunity and innate immunity are important components of the immune response and do not corelate with level of antibody titer. Thus, the clinical significance of decreasing titers is unknown.

Additionally, the recent United Kingdom study that estimated JYNNEOS effectiveness at 80% following the 2-dose primary series of JYNNEOS looked at cases that occurred from January 1 to December 31, 2023. As most people in this study received JYNNEOS from July 2022-March 2023, these findings further support the durability of JYNNEOS protection.

Based on currently available data from the unpublished CDC study, protection after the two doses JYNNEOS vaccine series does not wane for at least five years. Thus, booster doses are not recommended for anyone in the general population who was vaccinated during the ongoing clade II mpox outbreak in the United States that began in 2022.

Why does CDC recommend booster doses for certain healthcare providers and laboratorians with potential exposure to high levels of monkeypox virus?

Booster doses have always been recommended for certain laboratory workers at risk for orthopoxvirus infection due to their increased occupational risk. MPXV research laboratorians and certain clinical laboratorians (i.e., those performing orthopoxvirus and MPXV diagnostic testing) may work with high concentrations of virus (i.e., 100-1000 times higher than concentrations encountered from an mpox lesion) and occasionally experience needlestick accidents and other unusual virus exposures. For these reasons, booster doses are recommended every two years to maintain high levels of protection.

CDC recommendations on boosters may differ from those of some other countries.

Another country recently recommended a booster dose for people vaccinated two or more years ago, given studies showing a reduction in neutralizing antibodies in the two years following a two-dose primary vaccination. Although neutralizing antibody titers are known to decrease 6 months following the two-dose primary series, there is no established correlate of protection. This also does not consider that cell-mediated immunity and innate immunity are important components of the immune response and don't corelate with antibody titer levels. As noted above, CDC studies in DRC have shown a robust antibody response following booster doses up to five years following the primary vaccine series. This suggests that there would be a robust immune response from exposure to MPXV in a person vaccinated within the last five years. Therefore, at this time CDC does not recommend booster doses for those vaccinated during the ongoing clade IIb mpox outbreak, which began in 2022.

CDC vaccination recommendations for immunocompromised individuals may differ from those recommended by other countries.

Another country has recommended two doses plus a third dose at least 28 days after the second dose for immunocompromised individuals. There are data to support additional doses for immunocompromised individuals for some vaccine-preventable diseases. However, there are limited data to support this practice for JYNNEOS vaccine given the newness of its wide use. JYNNEOS has been studied as a 2-dose, double dose, and 3-dose series in patients with HIV, including those with low (<200 cells/mm³) CD4 counts. There was no significant difference in seroconversion rates with the addition of the third dose or by doubling the dose, with similar seroconversion rates across groups. Additional doses were discussed in the June 2023 meeting of the U.S. Advisory Committee on Immunization Practices (ACIP), and the ACIP did not believe the available data supported an additional dose in people who are immunocompromised. Therefore, CDC does not recommend additional doses of vaccine for that population.

CDC will continue to monitor JYNNEOS vaccination data from these and other studies.

Evaluating patients

Evaluating and counseling patients who could benefit from mpox vaccination is critical. To do so, healthcare professionals should perform a comprehensive social and sexual history.

Attention should be paid to sexual behaviors (e.g. frequency and types of sex) and partners (e.g. number and frequency), due to the populations that have been disproportionately affected by the ongoing clade II mpox outbreak.

Such evaluation should have health equity principles as a foundation and allow individuals to self-attest vaccine eligibility (i.e., providing mpox vaccination without requiring individuals to specify which criterion they meet).

Post-exposure prophylaxis (PEP)

Mpox vaccine can be given as post-exposure prophylaxis (PEP) both to people with known or presumed exposure to Monkeypox virus (MPXV). Mpox vaccine can also be given to people with certain risk factors and recent experiences that might make them more likely to have been exposed to mpox. As PEP, vaccine should be given as soon as possible, ideally within four days of exposure; administration 4 through 14 days after exposure may still provide some protection against mpox.

After 14 days, clinicians should consider the benefits of receiving vaccine on a case-by-case basis; benefits might still outweigh risks when administering vaccine in some clinical situations (e.g., for a severely immunosuppressed person with a recent sex partner confirmed to have mpox).

Any person with ongoing risk of mpox exposure should be offered vaccination, even if previously exposed, and regardless of time since exposure, as long as they have not yet developed signs or symptoms of mpox.

Vaccination given after the onset of signs or symptoms of mpox, after a diagnosis of mpox, or after recovery from mpox is not expected to provide benefit. At this time, naturally acquired mpox is believed to confer immune protection, although duration of immunity is unknown.

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, to make more doses available at a time when vaccine supply was limited. The authorized alternative regimen involves an intradermal (ID) route of administration with an injection volume of 0.1mL. 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. There is currently adequate supply of JYNNEOS vaccine. Therefore, clinicians can preferentially administer JYNNEOS via the subcutaneous route.

Vaccination schedule and dosing regimens for JYNNEOS vaccine

Duration of immunity

Peak immunity is expected to be reached 14 days after the second dose of JYNNEOS vaccine. Administration of additional vaccine doses (more than 2 doses) is currently not recommended for most people. For people at risk for occupational exposure to orthopoxviruses (e.g., certain research laboratoriansC), booster doses are recommended at 2-10 years depending on the type of work being performed. See ACIP Recommendations: Orthopoxviruses (Smallpox and Mpox) Vaccines.

Dosing intervals

Recommended interval: The second dose of JYNNEOS vaccine should be given 28 days (4 weeks) 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).

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.

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 (i.e., 28 days). 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."

Administration

Subcutaneous (Subcut) administration

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 and job aid [PDF – 1 page, 200KB].

Intradermal (ID) administration

Learn about intradermal administration of JYNNEOS.

Interchangeability of dosing regimens

In eligible individuals, the dosing regimens are interchangeable. For example, a person aged 18 years or older who received one JYNNEOS vaccine dose intradermally may receive a second dose subcutaneously at the recommended interval (i.e., 28 days) to complete the vaccination series. There is currently adequate supply of JYNNEOS vaccine. Therefore, clinicians can preferentially administer JYNNEOS via the subcutaneous route. Doses that were previously administered intradermally are equally effective as doses administered subcutaneously and do not need to be repeated.

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.

There is no required minimum interval between receiving any COVID-19 vaccine (i.e., Moderna, Novavax, or Pfizer-BioNTech) and JYNNEOS vaccine, regardless of which vaccine is administered first. People, particularly adolescent or 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 is at increased risk for mpox or severe disease due to COVID-19 disease, administration of JYNNEOS and COVID-19 vaccines should not be delayed.

JYNNEOS vaccine administration considerations for specific populations

Most adults age ≥18 years who are eligible for vaccination

There is currently adequate supply of JYNNEOS vaccine. Therefore, clinicians can preferentially administer JYNNEOS via the subcutaneous route.

For patients <18 years of age

Adolescents at risk for mpox may receive the JYNNEOS vaccine before an exposure. JYNNEOS is available for use as post exposure prophylaxis (PEP) for children and adolescents under 18 years determined to be at high risk for mpox under the Emergency Use Authorization (EUA) issued by the US Food and Drug Administration. Vaccination with JYNNEOS for children and adolescents aged <18 years should be administered via subcutaneous injection.

For patients <6 months of age, Vaccinia Immune Globulin Intravenous (VIGIV) should be considered in lieu of JYNNEOS vaccine. Clinicians should first contact their jurisdictional health department (Jurisdictional Contacts). Jurisdictional health departments can facilitate consultation with CDC and access to VIGIV.

People who are pregnant or breastfeeding

Available human data on JYNNEOS administered to people who are pregnant are insufficient to determine if there are any vaccine-associated risks in pregnancy. Studies of JYNNEOS vaccine in animals have shown no evidence of harm to a developing fetus.

While there are no data for people who are breastfeeding, animal data do not show evidence of reproductive harm; breastfeeding is not a contraindication to receiving JYNNEOS. It is not known whether JYNNEOS is excreted in human milk. Data are not available to assess the impact of JYNNEOS on milk production or the safety of JYNNEOS in breastfed infants. However, because JYNNEOS vaccine is replication-deficient, it likely does not present a risk of transmission to breastfed infants.

JYNNEOS can be offered to people who are pregnant or breastfeeding who are otherwise eligible. The risks and benefits of JYNNEOS should be discussed with the patient using shared clinical decision-making.

People with atopic dermatitis, eczema, or other exfoliative skin conditions

Studies evaluating JYNNEOS in people with atopic dermatitis have demonstrated immunogenicity in eliciting a neutralizing antibody response. No concerning safety signals were revealed.

People of any age who have a history of developing keloid scars

Administer 0.5mL subcutaneously.

People with congenital or acquired immune deficiency disorders, including those taking immunosuppressive medications and people living with HIV (regardless of immune status)

Administer as indicated based on age and history of keloids.

People with prior history of smallpox vaccination

Previous smallpox vaccination probably does provide some protection, but it may not necessarily be lifelong. During the 2003 mpox outbreak and during the ongoing clade II outbreak, several people who were infected with mpox had previously been vaccinated against smallpox decades prior. In response to the ongoing clade II outbreak, vaccines and other medical measures should be given to eligible people who were previously vaccinated against smallpox.

People with prior history of mpox

In the context of the ongoing clade II mpox outbreak the following are exceptions to the recommended two-dose series:

• A person who is diagnosed with mpox after their first dose of JYNNEOS is not recommended to receive the second dose at this time, because mpox likely confers additional immune protection.
• A person who would be eligible for vaccination but has been diagnosed with mpox is not recommended to be vaccinated at this time, because mpox infection likely confers immune protection.

For laboratorians

The only people recommended to receive booster vaccinations are certain research and diagnostic laboratorians who work with orthopoxviruses in a laboratory setting. It is not unusual for vaccine recommendations to differ for these laboratorians compared to others at risk for exposure to infections. Mpox research laboratorians work with research grade (i.e. high concentration) virus and occasionally experience needlestick accidents and other unusual exposures. Clinical laboratorians who test for mpox may similarly be at an increased risk. For these reasons, they are recommended to maintain high antibody levels via frequent booster doses.

Clinical laboratory personnel in hospitals (e.g., who handle blood, urine, and other bodily fluids from patients) are not recommended to receive booster doses at this time. As more data become available, recommendations may change.

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 intradermal administration would be appropriate if it is being considered. 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.

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.

Contraindications and precautions

JYNNEOS is contraindicated in patients with severe allergic reaction (e.g., anaphylaxis) after a previous dose, or to a vaccine component. JYNNEOS vaccine contains small amounts of gentamicin and ciprofloxacin and is produced using chicken embryo fibroblast cells. See package insert [PDF – 11 pages, 301 KB] for a full list of vaccine ingredients.

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).

People presenting with minor illnesses, such as a cold, may be vaccinated. People who are moderately or severely ill with or without fever should usually wait until they have recovered to their baseline state of health before routine vaccination; waiting might not be appropriate if vaccination is used for post exposure prophylaxis.

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 following requirements are stipulated as part of the HHS mpox vaccine provider agreement:

• 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
  • SeriousD adverse events (irrespective of attribution to vaccination)
  • Cases of cardiac events, including myocarditis and pericarditis
  • Cases of thromboembolic events and neurovascular events
• 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.

Resources

• JYNNEOS Package Insert
• JYNNEOS Vaccine Information Statement (VIS)
• JYNNEOS Vaccine Information Statement (VIS) in Spanish
• Vaccine Storage and Handling Toolkit
• JYNNEOS Standing Orders (Standard Regimen)
• Vaccination Operational Planning Guide
• FDA EUA Fact Sheet for Providers
• FDA EUA Fact Sheet for Patients and Caregivers
• FDA EUA Fact Sheet for Patients and Caregivers in Other Languages