Smallpox and Monkeypox (Mpox) disease & vaccine quick facts

Updated April 06, 2024

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Smallpox/Monkeypox (Mpox)

Smallpox is an illness caused by the variola virus, belonging to the orthopoxvirus family. When smallpox was circulating in the environment, there were several forms of the disease, with some more severe and life-threatening than others. In May 1980, smallpox was declared eradicated by the World Health Organization (WHO), with the last known case of smallpox reportedly in Somalia in October of 1977.
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 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 of feet once fever has resolved. These lesions then progress to blisters within 4 to 5 days, with crusting and scabbing of the lesions beginning about the ninth day fall off about 2 weeks after rash onset. Monkeypox (mpox), another orthopoxvirus, is similar in symptoms to smallpox but generally milder. Mpox infected individuals also develop swelling of the lymph nodes.
Complications of smallpox included severe bacterial infections of the skin and organs, sepsis, pneumonia, encephalitis (brain inflammation), and keratitis (inflammation of the cornea). 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. Historically, Variola Major was fatal in approximately 30 percent of cases. Complications of mpox include sepsis, encephalitis, eye infections that may result in blindness, bronchopneumonia, and other secondary infections. According the World Health Organization (WHO), death from mpox has historically occurred in 0 and 11 percent of cases. More recently, the WHO estimates death rates from mpox to be between 3 and 6 percent.
Smallpox is contagious, with transmission generally requiring extended face-to-face contact with an infected person. It can also be transmitted through respiratory droplets when an infected individual sneezes or coughs; however, is rarely an airborne virus. Coming into contact with scabs or the fluid (pus) in smallpox blisters can also cause smallpox infection.
In May 2022, the WHO reported an outbreak of monkeypox (mpox) illness in several countries where the virus was not endemic. The U.S. declared mpox as a public health emergency on August 4, 2022, which expired January 31, 2023.

Smallpox/Monkeypox (Mpox) 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 (mpox) vaccine, developed and manufactured by Bavarian Nordic approved for use in adults 18 years of age and older who are considered to be at high-risk of smallpox or mpox. The FDA has also issued an Emergency Use Authorization (EUA) for the use of the JYNNEOS vaccine to be given subcutaneously to high-risk persons under the age of 18, and intradermally (between the skin layers) to high-risk persons aged 18 and older. JYNNEOS is approved for use as an alternative to ACAM2000 in persons at risk for occupational exposure to orthopoxviruses. Booster doses of the vaccine have also been approved for persons who are at continued risk of exposure to orthopoxviruses.
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 (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. 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.
Clinical efficacy studies were not conducted on ACAM2000 and approval of the vaccine was based on immunogenicity studies that compared the vaccine to a previously licensed smallpox vaccine, Dryvax. According to the manufacturer, ACAM2000 was not inferior to Dryvax vaccine. A CDC funded study found that two doses of JYNNEOS vaccine was reported to be 66 percent effective against mpox, while a single dose, or partial vaccination, was reported to be only 35.8 percent effective.
Using the MedAlerts search engine, as of the CDC’s March 29, 2024 VAERS data release, there had been 7,817 adverse events reported to the Vaccine Adverse Events Reporting System (VAERS) in connection with smallpox-containing vaccines. Nearly 80 percent of smallpox vaccine-related adverse events occurring in adults 18-49 years of age. Of these smallpox-vaccine related adverse event reports to VAERS, 1,006 were classified as serious, and 23 deaths were reported. Over 65 percent of the reported deaths occurred in adults 18-49 years of age.
As of January 2024, ACAM 2000 and JYNNEOS vaccines are EUA vaccines and are considered a countermeasures. As such, U.S. vaccine manufacturers are shielded from vaccine injury liability claims. 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). 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)

Smallpox (Vaccinia) Vaccine, Live (ACAM 2000) Vaccine Product Insert & Licensing Information
Medical Guide for vaccination with ACAM2000
Smallpox and Monkeypox Vaccine, Live, Non-Replicating (JYNNEOS) Vaccine Product Insert & Licensing Information

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 (Mpox) and the smallpox/monkeypox (Mpox) 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.