Side Effects of the Smallpox Vaccine

Medically Reviewed by Dan Brennan, MD on December 08, 2022
3 min read

The smallpox vaccine prevents smallpox. For most people, it is safe and effective. Most people experience normal, typically mild reactions to the vaccine, which indicate that it is beginning to work. Some people may experience reactions that require medical attention.

The disease was declared to be eradicated worldwide in the late 1970s. However, the smallpox virus can be used as a bio-weapon, and there is a vaccine available for people who may encounter the agent.

These reactions to the smallpox vaccine usually go away without treatment:

  • The arm may be sore and red where the vaccine was given.
  • The glands in the armpits may become large and sore.
  • The vaccinated person may run a low fever.
  • 1 out of 3 people may feel bad enough to miss work, school, or recreational activity or have trouble sleeping.

In the past, about 1,000 people for every 1 million people vaccinated with the smallpox vaccine for the first time experienced reactions that, while not life-threatening, were serious. These reactions may require medical attention:

  • A vaccinia rash or outbreak of sores limited to one area. This is an accidental spreading of the vaccinia virus caused by touching the vaccination site and then touching another part of the body or another person. It usually occurs on the genitals or face, including the eyes, where it can damage sight or lead to blindness. Washing hands with soap and water after touching the vaccine site will help prevent this.
  • A widespread vaccinia rash. The virus spreads from the vaccination site through the blood. Sores break out on parts of the body away from the vaccination site (generalized vaccinia).
  • A toxic or allergic rash in response to the vaccine that can take various forms (erythema multiforme).

Rarely, people have had very bad reactions to the smallpox vaccine. In the past, between 14 and 52 people per 1 million people vaccinated for the first time experienced potentially life-threatening reactions. These reactions require immediate medical attention:

  • Eczema vaccinatum. Serious skin rashes caused by widespread infection of the skin in people with skin conditions such as eczema or atopic dermatitis.
  • Progressive vaccinia (or vaccinia necrosum). Ongoing infection of skin with tissue destruction frequently leading to death.
  • Postvaccinal encephalitis. Inflammation of the brain.

People with certain medical conditions -- including people with weakened immune systems or certain skin conditions -- are more likely to have these reactions and should not get the smallpox vaccine unless they have been exposed to smallpox.

Based on past experience, it is estimated that between one and two people out of every 1 million people vaccinated may die as a result of life-threatening reactions to the smallpox vaccine.

A massive program by the World Health Organization (WHO) wiped out all known smallpox viruses from the world in 1977, except for samples some governments saved for research purposes. The U.S. stopped giving the smallpox vaccine in 1972. In 1980, the WHO recommended that all countries stop vaccinating for smallpox. As a precaution against any possible exposure to smallpox, the drug tecovirimat (TPOXX) was approved for treatment of smallpox symptoms.