Smallpox Vaccine Safety

Key points

  • The virus that causes smallpox is part of the genus (group) Orthopoxvirus. Since 1980, smallpox has been considered eradicated.
  • The vaccines available that provide protection against smallpox can also provide cross-protection against other orthopoxviruses.
  • After smallpox eradication, routine vaccination against smallpox among the general public was stopped because it was no longer needed.

Overview

Smallpox is a serious infectious disease caused by the variola virus. The disease spreads easily from person to person, causing high fever, and a distinctive, progressive skin rash.

Reminder‎

This information is about the safety of smallpox vaccines. For the latest information about the safety of mpox vaccines, including side effects, please visit CDC's mpox vaccine safety site. For information about the current mpox outbreak, including information on symptoms and prevention, please visit CDC's mpox site.

Available vaccines & manufacturer package inserts

There are two types of vaccines licensed in the United States that can prevent smallpox disease. Both vaccines are made from a virus called vaccinia, which is a poxvirus similar to variola virus, but less harmful.

ACAM2000

See Also: Manufacturer package inserts and Vaccine Information Statement

JYNNEOS

  • Also known as Imvamune or Imvanex in other countries.
  • Approved for the prevention of smallpox and mpox.
  • The FDA approved JYNNEOS in 2019 for use in people ages 18 years and older and determined to be at high risk for smallpox or mpox infection.
  • This vaccine contains a poxvirus strain that does not cause clinical infections.
Keep Reading: Vaccine Information Statement

Who should & should not get the vaccine

General public

After smallpox eradication, routine vaccination against smallpox among the general public was stopped because it was no longer needed.

Keep Reading: Who Should Get Vaccination

Guidance for healthcare providers

Healthcare providers should consult CDC guidance for the most current information on who should or should not get a vaccine.

Keep Reading: Vaccination Information

Side effects

ACAM2000

Common side effects

  • Itching.
  • Swollen lymph nodes.
  • Sore arm.
  • Fever.
  • Headache.
  • Body ache.
  • Mild rash.
  • Fatigue (tiredness).

Serious side effects

  • Heart problems (including myocarditis and pericarditis).
  • Swelling of the brain or spinal cord.
  • Problems with the vaccination site blister, including infection.
  • Spreading the virus to other parts of the body or to another person.
  • Severe allergic reaction after vaccination.
  • Accidental infection of the eye (may cause swelling of the cornea, causing watery, painful eyes and blurred vision, scarring of the cornea, and blindness).

JYNNEOS

Common side effects

  • Injection site reactions, including pain, redness, swelling, hardening of the skin, and itching. Injection site reactions, except for pain, may occur more frequently after intradermal administration than after subcutaneous administration).
  • Headache.
  • Muscle pain.
  • Fatigue (tiredness).
  • Nausea.
  • Change in appetite.
  • Chills.
  • Fever.

When to call 911‎

Severe allergic reactions following vaccination are rare, but can be life threatening. If someone experiences symptoms of a severe allergic reaction, which can include hives, swelling of the face and throat, difficulty breathing, a fast heartbeat, dizziness, and weakness.

Vaccines, like any medicine, can have side effects. The most common side effects are usually mild and go away on their own.

Report possible adverse events to VAERS‎
‎

The Vaccine Adverse Event Reporting System (VAERS) is an early warning system, co-managed by CDC and FDA, that monitors for potential vaccine safety problems. Healthcare providers and vaccine manufacturers are required by law to report certain adverse events (any side effect or health problem after vaccination that is concerning to you, even if you are not sure if the vaccine caused the event) following vaccination to VAERS; patients and caregivers can also submit reports.

Submitting a Vaccine Adverse Event Reporting System (VAERS) Report and Using VAERS Data

A closer look at the safety data

ACAM2000

There are several serious adverse events that have been reported following the first vaccination or revaccination at a later date with ACAM2000.1These are serious risks and certain individuals who receive live vaccinia virus vaccine are more prone to these adverse events.

  • Myocarditis and pericarditis
    • The heart muscle and lining become inflamed. The package insert states the suspected cases were observed at a rate of 5.7 per 1,000 primary vaccinees.
  • General, progressive, and severe vaccinia
    • This condition can occur in immunocompromised people and is caused by the uncontrolled replication of the vaccinia virus. The virus causes open wounds, and depending on the severity, can lead to death.
  • Eczema vaccinatum resulting in permanent sequelae or death
    • This occurs when the vaccinia virus spreads and causes an overall rash and systemic reactions.
  • Fetal death
    • Pregnant people who have received a live vaccinia virus vaccine are more susceptible to spontaneous abortion (miscarriage).
  • Encephalitis, Encephalomyelitis and Encephalopathy
    • These are conditions of inflammation of brain, spinal cord, or both.
  • Erythema multiforme major (EMM), including Stevens-Johnson Syndrome (SJS)
    • EMM is a skin reaction from an infection or medication. SJS is a rare and serious disorder that affects skin, moist surfaces of the body (such as inside of mouth and throat), genitals, and eyes.
  • Ocular complications and blindness
    • When the vaccinia virus enters the eye region, it can cause eyelid infections, swelling, sensitivity to light, irritation and damage to the cornea, and possible blindness.

Acute ischemic cardiac events (ICE)2

In March 2008, ACAM2000 replaced the previous stockpiled smallpox vaccine, Dryvax®, as the only licensed smallpox vaccine at the time. While not routinely administered, ACAM2000 was administered to people entering military service and those working in labs handling variola (smallpox) virus. As part of the post-licensure marketing commitments for ACAM2000, FDA, CDC, Department of Defense, and the vaccine manufacturer, gathered additional safety data on adverse events following vaccination. In March 2011, a routine safety data review within Vaccine Adverse Event Reporting System (VAERS), co-managed by CDC and FDA, identified a safety concern of acute ischemic cardiac events (ICE) following ACAM2000 vaccination.

Researchers reviewed all reports to VAERS submitted from March 1, 2008 through June 30, 2013, following ACAM2000 vaccination. Possible ICE cases were identified by searching for specific medical terms, including myocardial ischemia (lack of blood flow back to the heart), acute myocardial infarction (heart attack), and ischemia (restriction of blood supply to any part of the body). A clinical review of the cardiovascular reports identified 16 cases of myocarditis/pericarditis (inflammation of the heart muscle or lining of the heart) and 15 ICE cases. This review did not confirm the concerns of ICE following ACAM2000. The study also suggested that with pre-vaccination screening of ACAM2000, cardiac events in a generally healthy population remain uncommon.

JYNNEOS

The overall JYNNEOS clinical trial program included 22 studies and a total of 7,859 people ages 18 through 80 years of age who received at least 1 dose of JYNNEOS. Findings included:

  • People with skin conditions (either active or history of skin conditions such as eczema or atopic dermatitis) who received JYNNEOS experienced mild to moderate skin reactions from the vaccine. No safety concerns were found during this study in people with skin conditions.3
  • During a study of the vaccine and placebo groups, there were three cases of heart palpitations, two cases of tachycardia, and no cases of myocarditis or pericarditis detected. Overall, data did not suggest an increased risk of myocarditis or pericarditis after vaccination with JYNNEOS compared with placebo controls.456
  • Across all 22 clinical trials, the safety profile of JYNNEOS was favorable in all populations, including people with HIV or other immunocompromising conditions. 7There were no clinically relevant differences in the safety or the reactogenicity of JYNNEOS in populations who were or were not previously exposed to a vaccinia virus vaccine.
  • The reported complications from live vaccinia virus vaccines, such as rashes caused by the virus (including generalized and progressive vaccinia), erythema multiforme (skin reaction from an infection or medication), or encephalitis, were not observed during the clinical trials for JYNNEOS.

How CDC monitors vaccine safety

CDC and the Food and Drug Administration (FDA) are committed to ensuring that vaccines provided to the public are safe and effective. Once vaccines are licensed or authorized for emergency use in the United States, CDC and FDA continuously monitor them through several safety systems.

Keep Reading: About Vaccine Safety Programs

Resources

Smallpox Vaccination: What Everyone Should Know
Everything you need to know about smallpox vaccine: who needs it, types of smallpox vaccines, how we...
Smallpox and Mpox ACIP Vaccine Recommendations
ACIP Recommendations on Smallpox, Mpox, and other MMWR articles. Advisory Committee on Immunization...
Smallpox Vaccination: Information for Healthcare Providers
Smallpox vaccine info for healthcare professionals: vaccine administration, expected reactions, take...
Interim Clinical Considerations for Use of JYNNEOS Vaccine for Mpox Prevention in the United States
Mpox Vaccine Considerations for Use of JYNNEOS Vaccine
Contraindications and Precautions
Contraindications and Precautions: General Best Practice Guidelines for Immunization. Advisory Commi...
Print
Content Source:
National Center for Emerging and Zoonotic Infectious Diseases (NCEZID)
  1. https://www.fda.gov/media/75792/download
  2. McNeil, M. M., Cano, M., R Miller, E., Petersen, B. W., Engler, R. J., & Bryant-Genevier, M. G. (2014). Ischemic cardiac events and other adverse events following ACAM2000(®) smallpox vaccine in the Vaccine Adverse Event Reporting System. Vaccine, 32(37), 4758–4765. https://doi.org/10.1016/j.vaccine.2014.06.034
  3. Greenberg, R. N., Hurley, M. Y., Dinh, D. V., Mraz, S., Vera, J. G., von Bredow, D., von Krempelhuber, A., Roesch, S., Virgin, G., Arndtz-Wiedemann, N., Meyer, T. P., Schmidt, D., Nichols, R., Young, P., & Chaplin, P. (2015). A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis. PloS one, 10(10), e0138348. https://doi.org/10.1371/journal.pone.0138348
  4. Overton, E. T., Lawrence, S. J., Wagner, E., Nopora, K., Rösch, S., Young, P., Schmidt, D., Kreusel, C., De Carli, S., Meyer, T. P., Weidenthaler, H., Samy, N., & Chaplin, P. (2018). Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial. PloS one, 13(4), e0195897. https://doi.org/10.1371/journal.pone.0195897
  5. Greenberg, R. N., Hay, C. M., Stapleton, J. T., Marbury, T. C., Wagner, E., Kreitmeir, E., Röesch, S., von Krempelhuber, A., Young, P., Nichols, R., Meyer, T. P., Schmidt, D., Weigl, J., Virgin, G., Arndtz-Wiedemann, N., & Chaplin, P. (2016). A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects. PloS one, 11(6), e0157335. https://doi.org/10.1371/journal.pone.0157335
  6. Zitzmann-Roth, E. M., von Sonnenburg, F., de la Motte, S., Arndtz-Wiedemann, N., von Krempelhuber, A., Uebler, N., Vollmar, J., Virgin, G., & Chaplin, P. (2015). Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population. PloS one, 10(4), e0122653. https://doi.org/10.1371/journal.pone.0122653
  7. Overton, E. T., Stapleton, J., Frank, I., Hassler, S., Goepfert, P. A., Barker, D., Wagner, E., von Krempelhuber, A., Virgin, G., Meyer, T. P., Müller, J., Bädeker, N., Grünert, R., Young, P., Rösch, S., Maclennan, J., Arndtz-Wiedemann, N., & Chaplin, P. (2015). Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial. Open forum infectious diseases, 2(2), ofv040. https://doi.org/10.1093/ofid/ofv040