Questions & Answers
Smallpox - Evidence of Immunity and Vaccination - Response Interpretation
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Evidence of Immunity Against Smallpox

  1. After vaccination, what evidence suggests an individual developed immunity against smallpox?

    Smallpox vaccination with live vaccinia virus causes the body to produce neutralizing IgG antibodies, as well as vaccinia-specific cell-mediated immunity. In a person with normal immune function, neutralizing antibodies appear about 10 days after primary vaccination and 7 days after revaccination. Clinically, people are considered fully protected after a successful response is demonstrated at the site of vaccination, about 7 days after vaccination.

    The vaccination site should be inspected 6 to 8 days after vaccination and the response interpreted at that time. The World Health Organization (WHO) Expert Committee on Smallpox defines two types of responses. The responses include:

    (a) a major reaction, which indicates that virus replication has taken place and vaccination was successful; or

    (b) an equivocal reaction, which either indicates (1) a possible consequence of immunity adequate to suppress viral multiplication or (2) allergic reactions to an inactive vaccine without production of immunity.

Major Reaction

  1. What is a "major reaction"?

    A "major reaction" is the internationally accepted term for a successful smallpox vaccination.

    Major (i.e., primary) reaction is defined as a vesicular (blister) or pustular lesion or an area of definite palpable induration (hardness) or congestion surrounding a central lesion that might be a crust or an ulcer. The usual progression of the vaccination site after primary vaccination is as follows:

    a. The inoculation site becomes reddened and itchy 3 to 4 days after vaccination.

    b. A vesicle (blister) surrounded by a red areola then forms, which becomes umbilicated (sunken center) and then pustular (pus-filled) by days 7 to 11 after vaccination.

    c. The pustule begins to dry, the redness subsides, and the lesion becomes crusted between the second and third week.

    d. By the end of about the third or fourth week, the scab falls off, leaving a permanent scar that at first is pink in color, but eventually becomes flesh-colored.

    Skin reactions after revaccination might be less pronounced with more rapid progression and healing than those after primary vaccinations. Revaccination is considered successful if a pustular lesion is present or an area of definite induration or congestion surrounding a central lesion (i.e., scab or ulcer) is visible upon examination 6 to 8 days after revaccination.

  2. What should I do if a re-vaccinee does not have a major reaction/take?

    An individual (a) born before 1972, or (b) employed as a health care worker before 1977, or (c) who travelled internationally before 1983, or (d) who was on active duty before 1991 or after 2002, or (e) who has a Jennerian scar and who does not have a cutaneous response ('major reaction' or 'take') following Smallpox vaccination is presumed to have been previously vaccinated and therefore, in accordance with the ACAM2000 package insert, does not require a second vaccination attempt to try to elicit a cutaneous response. The patient is considered adequately protected against smallpox (immune) and is fit for all military-related assignments, including deployment. No further diagnostic evaluation is required.

    A smallpox vaccinee not meeting the presumptive prior-vaccination criteria (above) who fails to demonstrate a cutaneous response ('major reaction' or 'take') after receiving 15 jabs with ACAM2000 requires a second vaccination attempt in accordance with current policy (reference?). If after a second attempt there is still no evidence of a cutaneous reaction the individual is considered adequately protected against smallpox (immune) for all military-related assignments, including deployment. No further diagnostic evaluation is required.

Equivocal Reaction

  1. What is an "equivocal reaction"?
    Equivocal reactions consolidate a variety of previous terms, including accelerated, modified, vaccinoid, immediate, early, or immune reactions. Equivocal reactions are defined as all responses other than "major reactions".

    If an equivocal reaction is observed, check vaccination procedures and repeat the vaccination by using vaccine from another vial, if available. It is often difficult to determine if the reaction was blunted by immunity, insufficiently potent vaccine, or vaccination technique failure. If the repeat vaccination using different vaccine fails to elicit a major reaction, health-care providers should consult an allergist or immunologist before attempting another vaccination.

No-Take Reaction

  1. I had a no-take reaction to my smallpox vaccination. Do I need to get another smallpox vaccination?
    An experienced healthcare provider should have determined whether you have had a successful smallpox vaccination by evaluating the vaccination site for a reaction. If this was your first vaccine in which there was no reaction, a second attempt to vaccinate should be made using a different vaccine lot and using a different vaccination site. This site may need to be checked more carefully and more often for a take reaction.

    If after your second smallpox vaccination there is still no evidence of a take reaction, you are considered immune to smallpox for military-related requirements, including deployment. Please contact the IHB if you have additional questions or concerns.