Expected Vaccine Reactions

This information is about preventing or responding to smallpox. For the latest information about the current mpox outbreak, including information on symptoms, prevention, and vaccines, please visit CDC’s Mpox site.

After vaccination, the vaccinia virus replicates in the epidermis of the skin. After 3 to 5 days, a papule forms at the site, then becomes vesicular (approximately day 5 to 8), then pustular, and usually enlarges to reach maximum size 8 to 10 days after vaccination. The pustule dries from the center outward and forms a scab. The scab separates 14 to 21 days after vaccination and usually leaves a pitted scar.

Determination of successful vaccination is made on days 6 to 8 after vaccination.

Normal reactions to the smallpox vaccine include:

  • Injection site reactions:
    • Erythema
    • Pruritus
    • Pain
    • Swelling
  • Constitutional symptoms:
    • Fatigue
    • Headache
    • Muscle aches and chills
    • Nausea
    • Fever over 100°F (37.8°C)
    • Malaise
  • Satellite lesions, which are benign, secondary vaccinial lesions proximal to the central vaccination lesion

Approximately one-third of adult primary vaccinees may feel sufficiently ill to miss work, school, or recreational activities, or may have trouble sleeping. More information about vaccination progression can be found in Smallpox Vaccination and Adverse Reactions, Guidance for Clinicians.