Smallpox and Monkeypox Disease & Vaccine Quick Facts


  • Smallpox is an illness caused by the variola virus, belonging to the orthopoxvirus family. There are several forms of smallpox illness, including Variola Major, modified-type smallpox, hemorrhagic smallpox, malignant (flat-type) smallpox, and Variola Minor. Variola Major was the most common form of the illness when smallpox was circulating in the environment.1
  • Initial symptoms of smallpox illness included anorexia, vomiting, malaise, high fever, chills, headache, backache, severe abdominal pain, pharyngitis, and extreme exhaustion. A rash might have also been visible in light-skinned individuals. Rash lesions would begin after the fever resolved and appear in the back of the mouth, behind the oral cavity (oropharynx), followed by the face, arms, and legs, and would eventually spread to the torso, palms, and soles. Within four days, rash lesions developed and progressed from macules to papules, then to vesicles within 4 to 5 days. In another one or two days, the vesicles evolved into round, firm pustules found deep in the dermis. Crusting and scabbing of the lesions usually began on the ninth day and the crusts generally began to fall off about 2 weeks after the onset of the rash.2 Monkeypox, another orthopoxvirus, is similar in symptoms to smallpox but generally milder. With monkeypox, infected individuals develop swelling of the lymph nodes.3
  • Complications of smallpox included severe bacterial infections of the skin and organs, sepsis, pneumonia, encephalitis (brain inflammation), and keratitis (inflammation of the cornea).4 The most common long-term health consequence of smallpox was scarring, which occurred all over the body but most often on the face. Additional sequelae included stillbirths and miscarriages, infertility in males, osteomyelitis, encephalitis, and blindness. Persons who recover from smallpox illness developed long-term immunity.5 Historically, Variola Major was fatal in approximately 30 percent of cases.6 Complications of monkeypox include sepsis, encephalitis, eye infections that may result in blindness, bronchopneumonia, and other secondary infections. According the World Health Organization (WHO), death from monkeypox has historically occurred in 0 and 11 percent of cases. More recently, the WHO estimates death rates from monkey pox to be between 3 and 6 percent.7
  • Smallpox is contagious; however, transmission generally requires extended face-to-face contact with an infected person. It can also be transmitted through respiratory droplets when an infected individual sneezes or coughs. The virus is rarely spread through airborne transmission – meaning the virus remains in the air for an extended period of time and may even circulate in a building’s ventilation system. Coming into contact with scabs or the fluid (pus) contained in the smallpox rash pustules or bedding and clothing that has come into contact with scabs or fluid can also cause smallpox infection.8 9
  • The last known case of smallpox reportedly occurred in Somalia in October of 1977. In May 1980, smallpox was declared eradicated by the World Health Organization (WHO). There are two known locations where smallpox virus is stored; the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and a laboratory outside of Moscow, Russia. Some government health officials believe that secret smallpox stores exist and could someday be used for bioterrorism.10

Smallpox/Monkeypox Vaccine

  • There are two smallpox vaccines approved by the U.S. Food and Drug Administration (FDA). The ACAM 2000 vaccine is a live smallpox (vaccinia) vaccine, developed and manufactured by Emergent Product Development Gaithersburg, Inc. approved for use in persons considered at high risk for smallpox infection. The JYNNEOS vaccine is a live, non-replicating, smallpox and monkeypox vaccine, developed and manufactured by Bavarian Nordic11 and approved for use in adults 18 years of age and older who are considered to be at high-risk of smallpox or monkeypox.
  • Serious adverse events reported following ACAM 2000 vaccination include encephalitis (brain inflammation), encephalomyelitis (inflammation of brain and spinal cord), encephalopathy (disease of brain causing alteration of brain function or structure), generalized vaccinia (systemic spread of the virus from the inoculation site), progressive vaccinia (vaccinia necrosum – death of bodily tissues), severe vaccinial skin infections, eczema vaccinatum, erythema multiforme major including Stevens-Johnson syndrome (severe and potentially life threatening skin and/or mucus membrane lesions), blindness, and fetal death in pregnant women. These complications have the potential to cause severe disability, permanent neurological deficits, and death.12
  • Serious adverse events reported during clinical trials for the JYNNEOS vaccine noted in the product insert include Crohn’s disease, sarcoidosis (inflammatory disease affecting organs), extraocular muscle paresis (weakening of eye muscles) and throat tightness.13 JYNNEOS is approved for use as an alternative to ACAM2000 in persons at risk for occupational exposure to orthopoxviruses. This includes laboratory personnel, healthcare providers administering ACAM2000 or those treating patients infected with orthopoxviruses. Booster doses of the vaccine have also been approved for persons who are at continued risk of exposure to orthopoxviruses.14
  • Using the MedAlerts search engine, as of the CDC's October 31, 2022 VAERS data release, there had been 7,064 adverse events reported to the Vaccine Adverse Events Reporting System (VAERS) in connection with smallpox-containing vaccines. Nearly 85 percent of smallpox vaccine-related adverse events occurring in adults 17-49 years of age. Of these smallpox-vaccine related adverse event reports to VAERS, 964 were classified as serious, and 20 deaths were reported. Over half of the reported deaths occurred in adults 17-49 years of age.
  • Smallpox and monkeypox vaccine manufacturers are shielded from liability under the 2005 Public Readiness and Emergency Preparedness (PREP) Act when a vaccine or drug developed in response to a health emergency causes the death or permanent injury of an individual who receives it during pre-licensure clinical trials or after it is released for public use.15 16 Individuals who die or suffer serious harm due to the administration of covered countermeasures, such as smallpox vaccines, may be eligible to receive compensation through the Countermeasures Injury Compensation Program (CICP).17 For more information on the liability shield and injury compensation, visit NVIC’s FAQ on Emergency Use Vaccines (EUA) & Vaccine Injury Compensation.

Food & Drug Administration (FDA)

Centers for Disease Control (CDC)

World Health Organization (WHO)

National Institute of Allergy & Infectious Diseases (NIAID)

NIAID on Smallpox

Vaccine Reaction Symptoms & Ingredients

NVIC’s Ask 8, If You Vaccinate webpage contains vaccine reaction symptoms and more.

Search for Vaccine Reactions

NVIC hosts MedAlerts, a powerful VAERS database search engine. MedAlerts examines symptoms, reactions, vaccines, dates, places, and more.

Reporting a Vaccine Reaction

Since 1982, the NVIC has operated a Vaccine Reaction Registry, which has served as a watchdog on VAERS. Reporting vaccine reactions to VAERS is required by federal law under the National Childhood Vaccine Injury Act of 1986. If your doctor will not report a reaction, you have the right to report a suspected vaccine reaction to VAERS.

IMPORTANT NOTE: NVIC encourages you to become fully informed about smallpox/monkeypox and the smallpox/monkeypox vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself. This information is for educational purposes only and is not intended as medical advice.


[1] U.S. Food and Drug Administration. Smallpox. Mar. 23, 2018.

[2] U.S Centers for Disease Control and Prevention. Clinical Disease. In: Smallpox. Dec. 5, 2016.

[3] U.S Centers for Disease Control and Prevention. Signs and Symptoms. In: Monkeypox. July 16, 2021.

[4] Johns Hopkins Bloomberg School of Public Health Center for Health Security. Variola Virus (Smallpox). Feb. 26, 2014.

[5] U.S Centers for Disease Control and Prevention. Clinical Disease. In: Smallpox. Dec. 5, 2016.

[6] U.S. Food and Drug Administration. Smallpox. Mar. 23, 2018.

[7] World Health Organization. Monkeypox. May 19, 2022.

[8] Mayo Clinic. Smallpox. In: Symptoms & causes. Sept. 22, 2020.

[9] U.S Centers for Disease Control and Prevention. Transmission. In: Smallpox. June 7, 2016.

[10] National Organization for Rare Disorders. Smallpox. In: Rare Disease Database. 2009.

[11] U.S Food and Drug Administration. Vaccines Licensed for Use in the United States. Jan. 31, 2022.

[12] Emergent Product Development Gaithersburg, Inc. ACAM2000 – Package Insert. U.S Food and Drug Administration. Dec. 13, 2019.

[13] Bavarian Nordic A/S Package Insert – JYNNEOS. U.S. Food and Drug Administration. June 21, 2021.

[14] Cosdon N. ACIP Updates Recommended Vaccines and Immunization Schedules after 2-Day Meeting. Contagion Live Nov. 3, 2021.

[15] U.S. Department of Health & Human Services. Public Readiness and Emergency Preparedness Act of 2005 (PREP Act). PREP Act Q&A. Jan. 7, 2022.

[16] Garde D, Branswell H. 6 burning questions Congress could push Covid-19 vaccine makers to answer todayStat News July 20, 2020.

[17] Health Resources & Services Administration. Countermeasures Injury Compensation Program (CICP). Nov. 2020.

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