A Look at Each Vaccine: Smallpox Vaccine

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When Cortez's army brought smallpox from Europe to the Western Hemisphere, about 4 million Aztecs died from the disease. In the early part of the 18th century, Boston, a city of 10,000 people, suffered an epidemic of smallpox — 5,000 people were infected and 800 died from the disease. Indeed, smallpox has probably killed more people in the history of the world than all other infectious diseases combined! About 300 million people have died from smallpox. However, because of the smallpox vaccine, first developed in the late 1700s, smallpox was eradicated. Eradicated means that it was completely eliminated from the face of the earth. Smallpox was declared to be eradicated by the World Health Organization (WHO) in 1980.

The disease

What is smallpox?

Smallpox is a virus. Symptoms of smallpox infection begin with a two- to five-day period of high fever, malaise and backache followed by the development of a rash. The rash begins in the lining of the mouth and throat as well as on the face and forearms before spreading to the trunk and legs. The rash starts with red bumps that are flat to the skin, but progresses to raised bumps, blisters and finally scabs. The time from the beginning of the rash to the formation of scabs is about two weeks.

The rash of smallpox is deeply embedded in the skin. Residual, life-long pockmarks on the skin often occur following resolution of the illness.

About 30 of every 100 people infected with smallpox will die from the disease.

How do you catch smallpox?

Smallpox is spread from one person to another by large droplets from the mouth and throat of people who have the disease. This means it is spread by coughing, sneezing or talking. Contact with an infected person must be fairly close (within about 6 feet) in order for spread to occur.

Smallpox is different from chickenpox in how it is spread. Whereas chickenpox virus (varicella) can be spread before the rash occurs, smallpox is only spread after the rash has occurred. The virus that is spread from one person to another is contained in the blisters that are located in the mouth and throat.

Usually it takes about 12 days from the time one is exposed to the virus for symptoms to begin.

The vaccine

What is the smallpox vaccine and how is it made?

The smallpox vaccine is made using a poxvirus that infects cows (cowpox). Cowpox causes disease in cows, but it rarely causes disease in humans. Because cowpox and human smallpox are similar, infection with cowpox can protect people against smallpox.

The person who first used cowpox to protect against smallpox was Edward Jenner in 1796. Jenner was a family physician who lived in southern England. He noticed that every few years, when smallpox would sweep across the English countryside, women who milked cows (milkmaids) were spared the infection. He reasoned that these women were getting infected when they came in contact with blisters on the udders of cows during milking, and that this infection was protecting them from infection with smallpox. So, he took fluid from the blisters of cows and injected it into several people (including his 15-month-old son) to see if that fluid protected against smallpox. It worked.

See an illustrated story of Edward Jenner’s experiment.

Vaccine success

Smallpox was the first human infection to be successfully eradicated. Eradication, which means elimination from the face of the earth, was accomplished by vaccination and public health procedures to track and contain the disease. The last case of natural smallpox occurred in Somalia in 1977, and the World Health Organization declared it to be eradicated in 1980. The success in eradicating smallpox provided hope for eradication of other devastating diseases, such as polio, rubella and measles. To date, the only other viruses to be eradicated include a virus that infected cattle, called rinderpest, and one of three types of polio virus [type 2].

How is the smallpox vaccine administered?

Because smallpox no longer occurs anywhere in the world, the general population is no longer vaccinated against it.

The smallpox vaccine is administered in a unique manner. A drop of the vaccine virus (called vaccinia) is placed on the upper arm. The drop is then inoculated into the skin using a two-pronged, stainless steel needle. The needle is used to puncture the skin three or 15 times (people getting their first vaccine get three punctures, whereas those getting a booster dose of vaccine receive 15 punctures). The vaccination often causes a residual, lifelong scar.

Since vaccination of the general population was stopped in the U.S. in 1972, people in their late 40s or older may still see this scar on their arm.

Does the smallpox vaccine have side effects?

The smallpox vaccine initially causes a red, raised bump at the site of inoculation that progresses to a blister and eventually a scab. The scab then separates from the skin about two weeks after inoculation.

Mild side effects from the vaccine include fever, swelling of the lymph node in the armpit near the site of inoculation, itching, sore arm, headache, body aches, mild rash or tiredness.

Severe side effects following administration of the smallpox vaccine do occur but are relatively uncommon:

  • In a small number of people, the smallpox vaccine can cause swelling of the heart or the tissue that surrounds it, leading to chest pain or pressure, fast or irregular heartbeat, or breathing problems. These can occur up to 4 weeks after receipt of the vaccine and should be brought to the attention of a healthcare provider as they can cause a medical emergency. 
  • Swelling of the brain or spinal cord
  • Bacterial infection of the vaccination site
  • Spread of the virus to other parts of the body, or even to other people, particularly if the recipient scratches the injection site and then touches another part of their body without washing their hands
  • Severe allergic reaction shortly after receipt of the vaccine, called anaphylaxis

While anyone can experience side effects, some people are at greater risk. These include those who:

  • Have eczema, atopic dermatitis or other skin issues
  • Have heart conditions or a family history of heart problems, including history of heart attack, congestive heart failure, stroke or other conditions
  • Smoke
  • Have high blood pressure, high cholesterol, diabetes, high blood sugar
  • Are pregnant or breastfeeding
  • Are less than 1 year old
  • Are using steroid-based eye medications
  • Had allergic reactions to previous doses or are allergic to neomycin or polymyxin B

Who should get the smallpox vaccine?

A different version of the smallpox vaccine was at one time given routinely to all children in the United States at about 1 year of age. By the 1960s, the risk of smallpox in the United States was dramatically reduced. Therefore, because the risks of the vaccine outweighed its benefits, routine administration of the smallpox vaccine to infants in the United States was discontinued in 1972. Administration to healthcare workers was discontinued in 1976, and administration to international travelers was discontinued in 1982.

Because smallpox no longer occurs anywhere in the world, the vaccine is not available for the public. Vaccination is only recommended for a very small number of people, including some lab workers that work with a related virus and some military personnel. Some military personnel are immunized because smallpox has been considered a potential weapon in a bioterrorism attack. If a bioterrorist attack were to occur, vaccine recommendations would likely be considered for the public as well.

Other questions you might have

How long does immunity to smallpox last?

The smallpox vaccine was discontinued for routine use in the United States in 1972. So, most people in this country younger than 50 years of age have never been vaccinated against smallpox. But what about people older than 50? Does immunity to smallpox last 50 years or longer?

The best study to answer this question was performed in England in the early 1900s. An outbreak of smallpox affecting more than 1,000 people occurred in Liverpool between 1902 and 1903. People infected with smallpox were divided into two groups: those who got smallpox vaccine in infancy and those who did not. The fatality rate for 30- to 49-year-olds was 3.7 percent in the vaccinated group and 54 percent in the unvaccinated group. For those older than 50 years of age, the fatality rate was 5.5 percent in the vaccinated group and 50 percent in the unvaccinated group.

Therefore, smallpox vaccine protected against disease caused by smallpox, even 50 years after vaccination.

Relative risks and benefits

Do the benefits of the smallpox vaccine outweigh its risks?

No. Smallpox infections no longer occur in the world. Currently, the risks of the vaccine clearly outweigh its benefits. However, if smallpox infections were to occur again in the United States, the relationship between vaccine risks and benefits would change dramatically.

Disease risks

  • Although this disease is deadly, no cases occur anywhere in the world, so the risk today is zero. Because there is no risk of disease, this is a situation in which the use of a vaccine does NOT outweigh the risks of disease.

Vaccine risks

  • Inflammation of heart or tissues surrounding heart
  • Infection of the inoculation site
  • Inadvertent inoculation of another site or other people
  • Swelling of brain or spinal cord
  • Severe allergic reaction
  • Rarely death


Plotkin SA, Orenstein W, Offit PA, and Edwards KM. Smallpox and vaccinia in Vaccines, 7th Edition, 2018, 1001-1030.

Cohen, J. Smallpox vaccinations: how much protection remains? Science 2001: 294:885.

Reviewed by Paul A. Offit, MD on May 19, 2020

Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family's personal health. You should not use it to replace any relationship with a physician or other qualified healthcare professional. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult your physician or, in serious cases, seek immediate assistance from emergency personnel.