Primary prevention

Vaccination is recommended to prevent infection with mpox. Smallpox vaccines are used for this purpose, although these vaccines are now also approved for the prevention of mpox. Vaccines are based on the vaccinia virus because it is less harmful than the variola virus, and due to the cross-protection afforded by the immune response to orthopoxviruses. Although routine vaccination against smallpox ceased in the 1970s, vaccines are stockpiled in most countries in case of an emergency. Vaccine availability varies between countries and you should consult your local public health authority for guidance on how to obtain and use vaccines.

Attenuated live virus (replication-deficient) vaccines

  • Attenuated live virus (replication-deficient) vaccines are third-generation vaccines based on modified vaccinia Ankara (available as modified vaccinia Ankara Bavarian Nordic strain, or MVA-BN).

    • These vaccines represent more attenuated vaccine strains compared with first- and second-generation vaccines (see below), specifically developed by further passage in cell culture or animals.

    • Vaccines are typically administered subcutaneously (two doses given 28 days apart), and protection begins 2 weeks after the second dose (i.e., maximum protection takes 6 weeks). A third dose has been recommended in immunocompromised people in some countries, but there are no data to support additional doses.[148]

    • Intradermal administration (fractional dosing at one fifth the usual dose) may be recommended in outbreak situations where there are supply constraints.[149][150]​ The lower intradermal dose was found to be immunologically noninferior to the standard subcutaneous dose in one study. However, there is an increased risk of local reactions after intradermal injection.[151] An observational study found that intradermal administration was associated with a high incidence of mild to moderate local shot-site reactions. Systemic adverse reactions were reported in 39% of patients after the first dose (26% after the second dose), but serious adverse events were rare.[152]

    • Consult your local public health authority for more information.

  • Third-generation vaccines are available for the prevention of mpox, although supply may be limited in some countries. MVA-BN is available under different brand names (e.g., Imvanex®, Imvamune®, and Jynneos®).

    • Imvanex® is approved in the UK and Europe for active immunization against mpox.

    • Jynneos® is approved in the US for the prevention of mpox in adults ≥18 years of age. The Food and Drug Administration has issued an emergency use authorization to also allow the use of Jynneos® in people <18 years of age who are at high risk of infection. The emergency use authorization also allows for the two doses of Jynneos® to be administered intradermally in adults ≥18 years of age who are at high risk for infection.[153]

    • Jynneos® may be available in the UK during periods of limited vaccine supply; however, the conditions of regulatory approval in the UK vary slightly from those in the US.[154] The UK Health Security Agency (UKHSA) and the European Medicines Agency support intradermal dosing in healthy adults (including pregnant women, but not immunocompromised people) during periods of limited vaccine supply.[155][156][157]

    • LC16 (a minimally-replicating vaccine) may be available in some countries (e.g., Japan).[158][159]

  • Third-generation vaccines are considered to be safer compared with first- and second-generation vaccines. However, safety data are limited.

    • Replication-deficient vaccines have fewer contraindications and cautions, and are associated with fewer serious adverse events compared with replication-competent vaccines.

    • A history of a severe allergic reaction (e.g., anaphylaxis) to a previous dose of the vaccine is a contraindication. Caution is required in people who have a history of a severe allergic reaction to a component of the vaccine (e.g., gentamicin, ciprofloxacin, chicken or egg protein) or an acute illness. There is no risk for inadvertent inoculation and autoinoculation.

    • A phase 3 trial found that immune responses with Jynneos® were not inferior compared with patients who received ACAM2000®, and no safety concerns were identified. Typical severe adverse effects associated with replication-competent vaccinia virus strains were not observed. However, the trial was small (220 participants received at least one dose of Jynneos®) and the follow-up time was limited to 29 days.[160]

    • The risk of myocarditis after third-generation vaccines (e.g., Jynneos®) is currently unknown. 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 a third-generation vaccine.[161]

    • Data from the US Vaccine Adverse Event Reporting System (VAERS) based on vaccination during the 2022 global clade II mpox outbreak indicates that the safety profile of Jynneos® is consistent with prelicensure studies, and that serious adverse events (e.g., anaphylaxis, myocarditis) were rare among adults.[162]​ However, cardiovascular events following two doses were significantly more common compared to placebo.[163]

    • Symptoms of vaccinia have been reported after vaccination with Jynneos®.[164]

  • Third-generation vaccines are preferred in certain patient populations.

    • ​Nonreplicating vaccines are generally preferred in immunocompromised people (including those with HIV), pregnant and breast-feeding women, and children and adolescents (use in children may be off-label).[150]​​

    • Safety and efficacy data in immunocompromised people, including those with HIV infection, are limited. The MVA-BN vaccine can be offered to immunocompromised people and those with HIV, if indicated, after a discussion of the risks and benefits and using shared decision-making. Timing of vaccination should take into account planned or current immunosuppressive therapies.[35][36]​​ However, immunogenicity among people with CD4 counts <100 cells/microliter or who are not virologically suppressed remains unknown.​[165]

    • There are insufficient data to determine the risks of these vaccines in pregnant and breast-feeding women. However, the vaccine can be offered to pregnant and breast-feeding women who are otherwise eligible, after a discussion of the risks and benefits and using shared decision-making.[127]

    • Safety data in children are limited. However, one study found that a single dose of MVA-BN was well-tolerated.[166]

Live replication-competent vaccines

  • First-generation vaccines (e.g., Dryvax®, Wetvax®/Aventis Pasteur smallpox vaccine) and second-generation vaccines (e.g., ACAM2000®) are not available to the general public. However, they may be stockpiled in case of an emergency.

    • First-generation vaccines from the smallpox eradication program may be held in national reserves but do not meet current safety and manufacturing standards and are not recommended at this time.

    • ACAM2000® is approved in the US for the prevention of mpox in people who are at high risk for infection.

    • These vaccines are administered percutaneously as a single dose using a multiple puncture technique with a bifurcated needle. If inoculation is successful, a lesion develops at the site of vaccination (known as "a take"). Protection occurs within 28 days. Duration of immunity is unknown.

  • Contraindications include history of severe allergic reaction (e.g., anaphylaxis) after a previous dose of the vaccine, atopic dermatitis, other exfoliative skin conditions, immunosuppression (congenital or acquired), history of drugs or treatments that cause immunosuppression, HIV infection (regardless of immune status), transplant recipients, autoimmune disease, eye disease being treated with topical corticosteroids, pregnancy and breast-feeding, age <1 year, allergy to vaccine component, and underlying heart disease or cardiac risk factors.​[167]

    • Although first- and second-generation vaccines are usually contraindicated in pregnant women, a systematic review and meta-analysis found that the overall risk associated with maternal vaccination appears to be low. Outcomes of vaccination in 12,201 pregnant women were included. No association with spontaneous abortion, preterm birth, or stillbirth was identified. Vaccination in the first trimester was associated with a small increased risk of congenital defects (based on limited data). While fetal vaccinia appears to be a rare consequence of maternal vaccination, it is associated with a high rate of fetal loss.[168]

  • Inoculation with traditional vaccinia may cause eczema vaccinatum, generalized vaccinia, or potentially fatal progressive vaccinia (see Complications).[169]

    • There are many other potential adverse effects including superinfection of the vaccination site or regional lymph nodes, cellulitis, unintentional transfer of vaccinia virus (e.g., accidental autoinoculation of other body parts, ocular vaccinia, inoculation of close household contacts), fetal vaccinia, myopericarditis, dilated cardiomyopathy, cardiac ischemia, encephalitis and other severe neurologic manifestations, and even death.

    • The risk of myopericarditis was 3.6-fold higher in vaccinated military personnel compared with unvaccinated after administration of the ACAM2000® vaccine, and usually occurred within 8 to 14 days (up to 6 weeks).[170] However, the true risk may be higher. Fatal cases have been described.[171] For more information see Complications.

    • Vaccine adverse events may be managed with vaccinia immune globulin and antiviral agents.

Mass vaccination is not recommended for mpox outbreaks or for the general public. However, pre-exposure vaccination may be recommended in certain groups of people where appropriate vaccines are available, taking into account the possibility of limited supply.

  • The World Health Organization (WHO) recommends pre-exposure vaccination for laboratory personnel working with orthopoxviruses, with periodic revaccination considered every 2-5 years for people who are at high risk of exposure to more virulent orthopoxviruses. In the context of an mpox outbreak, the WHO recommends pre-exposure vaccination for people at high risk of exposure, including:[150]

    • Members of a geographically defined area or community, including children, with a documented high risk of exposure to people with mpox, based on local epidemiology.

    • Sex workers, gay, bisexual, or other men who have sex with men with multiple sexual partners, or other individuals with multiple casual sexual partners.

    • Healthcare workers at risk of repeat exposure.

    • Clinical laboratory and healthcare personnel performing diagnostic testing for mpox or providing care.

    • Outbreak response team members as designated by national public health authorities.

  • The WHO recommends certain vaccines in special populations.

    • Immunocompetent nonpregnant adults: any appropriate second- or third-generation vaccine (e.g., MVA-BN, LC16, ACAM2000®) is recommended.

    • Children and adolescents: nonreplicating or minimally replicating vaccines are recommended. MVA-BN is not currently licensed for people <18 years; however, it may be used in the context of an outbreak when the benefits of vaccination outweigh the potential risks. LC16 is only approved in Japan for use in children.

    • Pregnant women: nonreplicating vaccines are recommended.

    • Immunocompromised: nonreplicating vaccines are recommended in immunocompromised people for whom replicating or minimally replicating vaccines are contraindicated.

  • In the UK, the UK Health Security Agency (UKHSA) recommends pre-exposure vaccination with MVA-BN for:

    • Occupational vaccination: smallpox-naive individuals at risk of exposure on the basis of an occupational health assessment (e.g., healthcare workers or designated staff in hospital units due to care for a patient with mpox) or staff working in sexual health services who have been identified as assessing suspected cases, even if they will be wearing full personal protective equipment.[155]

    • Targeted pre-exposure vaccination: men who have sex with men at highest risk due to a large number of contacts (i.e., using markers of high-risk behavior similar to those used to assess eligibility for HIV pre-exposure prophylaxis such as history of multiple partners, participation in group sex, and attending sex-on-premises venues).[172]

    • UKHSA: recommendations for the use of pre and post exposure vaccination during an mpox incident Opens in new window

    • UKHSA: mpox (monkeypox) outbreak - vaccination strategy Opens in new window

  • In the US, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) recommends pre-exposure vaccination with Jynneos® for the following populations:[148]

    • People at risk for occupational exposure to orthopoxviruses (as an alternative ACAM2000®)

    • People ages ≥18 years at risk of mpox during an mpox outbreak, including travelers to affected countries who anticipate the following activities: sex with a new partner; sex at a commercial sex venue; sex in exchange for money, goods, drugs, or other trade; or sex in association with a large public event.

    • Gay, bisexual, and other men who have sex with men, transgender, or nonbinary people ages ≥18 years 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; 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, or people who anticipate experiencing any of the risks described are also eligible).

    • CDC: vaccine for mpox prevention in the United States Opens in new window

  • The CDC also recommends pre-exposure vaccination with either Jynneos® or ACAM2000® for:[161]

    • People who are at occupational risk for exposure to orthopoxviruses (e.g., research laboratory personnel who work with orthopoxviruses, clinical laboratory personnel who perform diagnostic testing for orthopoxviruses, designated response team members)

    • People who administer live replication-competent vaccines (e.g., ACAM2000®)

    • People who care for patients with infection with replication-competent orthopoxviruses

  • Booster doses may be recommended in certain populations.

    • In the US, the ACIP recommends a booster dose in people who are at ongoing risk for occupational exposure to orthopoxviruses.​

      The booster dose is recommended every 2 years (Jynneos®) or 3 years (ACAM2000®) for people working with more virulent orthopoxviruses such as variola virus or monkeypox virus, or every 10 years (Jynneos® or ACAM2000®) for those working with less virulent orthopoxviruses such as vaccinia virus.[161]

    • Booster doses are not currently recommended by the CDC for the general population vaccinated during the ongoing outbreak as protection from the two-dose series does not wane for at least 5 years (based on currently available unpublished CDC data).[148] However, there is emerging observational evidence of waning immunity by 12 months.[173]

    • Guidelines for booster doses may vary between geographic locations and guidelines.

  • People who have recovered from mpox are not recommended to receive vaccination as recovery from the infection, regardless of clade, likely confers protection from either clade of the virus.[148]

Limited evidence suggests that smallpox vaccines provide protection against mpox.

  • Data acquired from the final stages of the smallpox eradication program implied that first- and second-generation vaccines yielded 85% protection upon subsequent exposure to mpox.[94]

    • One systematic review found that prior immunization with the smallpox vaccine yielded 81% protection against mpox, and that immunity provided by the vaccine is long lasting. However, the review only included six studies with approximately 2000 participants, and most studies had a high risk of selection bias.[174]

    • Antibodies elicited by first-generation vaccines have recently been found to neutralize the clade II monkeypox virus, the virus responsible for the 2022 global clade II mpox outbreak, more than 40 years after administration of the vaccine.[175]

    • Differences in the appearance of the rash have been noted in vaccinated versus unvaccinated people. Vaccinated people tend to have fewer lesions, smaller lesions, and better representation of the centrifugal distribution.[176]

  • Approval of third-generation vaccines was based on data from animal studies that showed protection against mpox in nonhuman primates.[177] Safety and efficacy in humans was inferred from these animal studies.

    • A two-dose MVA-BN series was shown to yield relatively low levels of neutralizing antibodies in nonprimed individuals in one study. However, the role of these neutralizing antibodies as a correlate of protection against transmission and disease is currently unclear.[178]

  • Limited data are available on the efficacy of third-generation vaccines used during the 2022 global clade II mpox outbreak.

    • No randomized clinical trials of vaccination against mpox have been conducted.

    • Real-world observational data from the US demonstrates a reduced incidence of mpox among vaccinated men ages 18-49 years. Protection was higher after two doses (86%) compared with one dose (75%).[179] However, one dose may be moderately effective against infection, and may attenuate disease severity and reduce the risk of hospitalization in people who become infected after vaccination compared with unvaccinated people.[180][181]​​

    • Vaccine efficacy has been reported to be 66% (full vaccination with 2 doses) and 36% (partial vaccination with one dose).​[182]

    • A systematic review and meta-analysis found that a single dose of Jynneos® had an efficacy rate of 78%.[183]

    • There have been reports of breakthrough infections in previously vaccinated people (<1% of people vaccinated with two doses).[148][184][185][186]​​​​​​

    • There is limited evidence for a milder disease course in patients with a history of childhood smallpox vaccination, but hospitalization rates were not lower in vaccinated people.[187]

    • Jynneos® (a third-generation vaccine) resulted in a better humoral response compared with ACAM2000® (a second-generation vaccine) in one study.[188]

Resources on vaccination are available from public health authorities; check your local guidance.

Other vaccines are also in development. A fourth-generation vaccine (VACΔ6) is available in the Russian Federation.

Secondary prevention

Postexposure vaccination may be recommended in specific groups of people to prevent or attenuate infection. For more information on vaccines, see Primary prevention.

  • The World Health Organization recommends postexposure vaccination with an appropriate second- or third-generation vaccine for contacts of cases, ideally within 4 days of first exposure (and up to 14 days in the absence of symptoms).[150]​​

  • In the UK, the UK Health Security Agency (UKHSA) recommends risk assessing people and offering postexposure vaccination with a single dose of MVA-BN if appropriate as soon as possible and within 4 days after an identified exposure.[155]

    • Postexposure vaccination may be extended up to 14 days for those at high risk of ongoing exposure (e.g., men who have sex with men, healthcare workers where the dose will act as their first pre-exposure dose), and those who are at risk of more severe disease (e.g., immunocompromised people, pregnant women, children ≤5 years of age).

    • Postexposure vaccination may be temporarily restricted to contacts at highest risk of severe illness during periods of limited vaccine supply (e.g., immunocompromised people, pregnant women, children ≤5 years of age).[157]

    • People with HIV infection who are immunosuppressed (i.e., CD4 count <200 cells/microliter, persistent viremia, or immunosuppression related to another condition or treatment) should receive two full subcutaneous doses. People with CD4 counts >200 cells/microliter and viral suppression can receive intradermal fractionated dosing. Slightly lower antibody responses can occur after the first dose, but the difference is less compared with people without HIV after the full vaccine course.[165]

    • UKHSA: recommendations for the use of pre and post exposure vaccination during an mpox incident Opens in new window

  • In the US, the Centers for Disease Control and Prevention (CDC) recommends postexposure vaccination after known or presumed exposure with two doses of Jynneos®, ideally within 4 days and up to 14 days (use can be considered on a case-by-case basis after 14 days). It may also be given to people with risk factors or recent experiences that make them more likely to have been exposed to mpox.[148]

    • Postexposure vaccination is recommended for contacts with high-risk exposures, and may be considered for contacts with intermediate-risk exposures (see Screening).[257]​​

    • Immunocompromised: postexposure vaccination with Jynneos® can be offered to immunocompromised people including those with HIV infection, if indicated, after a discussion of the risks and benefits and using shared decision-making. Timing of vaccination should take into account planned or current immunosuppressive therapies; however, postexposure vaccination should not be delayed. The antiviral medication tecovirimat and vaccinia immune globulin may be considered for postexposure prophylaxis in patients with severe immunodeficiency in T-cell function on an individual case-by-case basis if an alternative option to vaccination is required, but the efficacy of these therapies for this indication is unknown.[35][36]

    • Children and adolescents: postexposure vaccination with Jynneos® may be offered to children and adolescents who are otherwise eligible. Vaccination should be offered to sexually active adolescents who were exposed to mpox. Adolescents at risk of mpox may also receive the Jynneos® vaccine before an exposure. Data on the safety and efficacy of postexposure vaccination in children and adolescents are limited. Vaccinia immune globulin should be considered for postexposure prophylaxis in infants <6 months of age in lieu of vaccination. Antivirals (e.g., tecovirimat) may be considered in unusual circumstances (e.g., if vaccination is contraindicated), but the efficacy of these therapies for this indication is unknown.[34]

    • Pregnant and breast-feeding women: postexposure vaccination with Jynneos® can be offered to pregnant and breast-feeding women who are otherwise eligible, after a discussion of the risks and benefits and using shared decision-making.[127]

  • The dose for postexposure vaccination may differ between countries and you should consult your local public health authority.

    • The recommended dose schedule for postexposure vaccination with a nonreplicating vaccine is generally two doses (given 28 days apart).

    • However, some countries may recommend only one dose for postexposure vaccination (two doses may be recommended in certain patients, such as those with HIV infection), and some countries may recommend three doses (e.g., in patients with HIV infection and low CD4 counts depending on vaccination history). However, data on these regimens are limited.[392]

    • Intradermal dosing may be used for postexposure vaccination in healthy adults (see above).

Postexposure vaccination of close contacts has successfully limited transmission of mpox in past outbreaks, and can abort infection or significantly attenuate it.[393]

  • Vaccination with standard first- or second-generation vaccinia virus vaccines was demonstrated through several observational studies to be about 85% effective in preventing mpox.[94] However, there is very limited evidence on whether third-generation vaccines prevent or modify disease when given to contacts after exposure.

  • Vaccination up to 14 days postexposure is thought to be beneficial.[394] There is a theoretical possibility of attenuating disease if vaccination occurs towards the end of the range of the incubation period.

  • Real-world data from the 2022 global clade II mpox outbreak indicates that the incidence of mpox among males ages 18 to 49 years who were recommended to receive postexposure vaccination with Jynneos® was 14 times higher among unvaccinated people compared with those who had received their first vaccine dose ≥14 days earlier. However, there are numerous limitations to these data.[395]

    • Observational studies report vaccine efficacy to be between 36% and 89% after one dose, and between 66% to 86% after two doses. However, these studies have various limitations.[396][397][398][399][400]

    • Neutralizing antibody responses at 6 months have been found to be much lower in vaccinated people compared with those with previous natural infection.[401]

    • Breakthrough infections have been reported.[402][403][404]

Use of this content is subject to our disclaimer