A Look at Each Vaccine: Smallpox Vaccine

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 has been eliminated from the face of the earth.

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. Smallpox virus 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 to the beginning of symptoms.

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 humans 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.

Vaccine success

Smallpox was the first human infection to be successfully eradicated by vaccination (one type of poliovirus [type2] has also now been eliminated). By 1977, smallpox, the most feared and devastating of all infectious diseases, was eliminated from the face of the earth. The last case of natural smallpox occurred in Somalia. Our success in eradicating smallpox has provided hope for eradication of other devastating diseases, such as polio, rubella and measles.

How is the smallpox vaccine administered?

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 1971, people in their 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 and swelling of the lymph node in the armpit near the site of inoculation. About 70 of 100 people given the vaccine will have fever greater than 100° Fahrenheit. The fever usually begins about four days after inoculation.

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

  • About five of every 10,000 people given the vaccine will inadvertently transfer the virus from the site of inoculation to another site (usually the eyelid, face, nose, mouth, genitals or rectum). Inadvertent inoculation can cause swelling, tenderness and rash at the site of transfer.
  • About two of every 10,000 people given the vaccine will develop a generalized rash that spreads to the body. The generalized rash occurs more commonly in people with eczema.
  • About one of every 100,000 people who get the smallpox vaccine will develop an infection of their brain called encephalitis.
  • About one of every 25,000 people given the vaccine will develop inflammation of the heart muscle (myocarditis) or inflammation of the membrane that surrounds the heart (pericarditis) or both.
  • About one of every 1 million people given the smallpox vaccine will develop a severe progressive form of the disease that is often fatal. These people usually have severe immunologic deficits prior to receipt of the vaccine.

Who should get the smallpox vaccine?

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 1971. 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; however, smallpox has been considered a potential weapon in a bioterrorism attack. For this reason, some military personnel are immunized with the smallpox vaccine. 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 the early 1970s. So, most people in this country younger than 40 years of age have never been vaccinated against smallpox. But what about people older than 40? Does immunity to smallpox last 40 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 (Cohen, J. Smallpox vaccinations: how much protection remains? Science 2001;294:885).

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

  • Fever greater than 100 degrees Fahrenheit (70 of 100 people)
  • Inadvertent inoculation of another site (5 of 10,000 people)
  • Rash spread over body (2 of 10,000 people)
  • Encephalitis (swelling of brain – 1 of 100,000 people)
  • Inflammation of heart or tissues surrounding heart (1 of 25,000 people)
  • Fatal disease (1 of 1 million people, most often someone who was suffering an immune deficiency)


Plotkin SA, Orenstein W, and Offit PA. Smallpox and vaccinia in Vaccines, 6th Edition, 2012, 718-745.

Reviewed by Paul A. Offit, MD, Lori Handy, MD, MSCE on May 01, 2017

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.