Dryvax,® the vaccinia (smallpox) vaccine currently licensed in the United States, is a lyophilized, live-virus preparation of infectious vaccinia virus (Wyeth Laboratories, Inc., Marietta, Pennsylvania). Vaccinia vaccine does not contain smallpox (variola) virus. Previously, the vaccine had been prepared from calf lymph with a seed virus derived from the New York City Board of Health (NYCBOH) strain of vaccinia virus and has a minimum concentration of 108 pock-forming units (PFU)/ml. Vaccine was administered by using the multiple-puncture technique with a bifurcated needle. A reformulated vaccine, produced by using cell-culture techniques, is now being developed.
Vaccine Efficacy
Neutralizing antibodies induced by vaccinia vaccine are genus-specific and cross-protective for other Orthopoxviruses (e.g., monkeypox, cowpox, and variola viruses) (16--18). Although the efficacy of vaccinia vaccine has never been measured precisely during controlled trials, epidemiologic studies demonstrate that an increased level of protection against smallpox persists for <5 years after primary vaccination and substantial but waning immunity can persist for >10 years (19,20). Antibody levels after revaccination can remain high longer, conferring a greater period of immunity than occurs after primary vaccination alone (3,19). Administration of vaccinia vaccine within the first days after initial exposure to smallpox virus can reduce symptoms or prevent smallpox disease (2--4).
Although the level of antibody that protects against smallpox infection is unknown, after percutaneous administration of a standard dose of vaccinia vaccine, >95% of primary vaccinees (i.e., persons receiving their first dose of vaccine) will experience neutralizing or hemagglutination inhibition antibody at a titer of >1:10 (21). Neutralizing antibody titers of >1:10 persist among 75% of persons for 10 years after receiving second doses and <30 years after receiving three doses of vaccine (22,23). The level of antibody required for protection against vaccinia virus infection is unknown also. However, when lack of local skin response to revaccination with an appropriately administered and potent vaccine dose is used as an indication of immunity, <10% of persons with neutralizing titers of >1:10 exhibit a primary-type response at revaccination, compared with >30% of persons with titers <1:10 (24). Lack of major or primary-type reaction can indicate the presence of neutralizing antibody levels sufficient to prevent viral replication, although it can also indicate unsuccessful vaccination because of improper administration or less potent vaccine.
Side Effects and Less Severe Adverse Reactions. In a nonimmune person who is not immunosuppressed, the expected response to primary vaccination is the development of a papule at the site of vaccination 2--5 days after percutaneous administration of vaccinia vaccine. The papule becomes vesicular, then pustular, and reaches its maximum size in 8--10 days. The pustule dries and forms a scab, which separates within 14--21 days after vaccination, leaving a scar (Figure 3). Primary vaccination can produce swelling and tenderness of regional lymph nodes, beginning 3--10 days after vaccination and persisting for 2--4 weeks after the skin lesion has healed. Maximum viral shedding from the vaccination site occurs 4--14 days after vaccination, but vaccinia can be recovered from the site until the scab separates from the skin (50).
A fever is also common after the vaccine is administered. Approximately 70% of children experience >1 days of temperatures >100 F for 4--14 days after primary vaccination (21), and 15%--20% of children experience temperatures >102 F. After revaccination, 35% of children experience temperatures >100 F, and 5% experience temperatures of >102 F (24). Fever is less common among adults after vaccination or revaccination (CDC, unpublished data, undated).
Inadvertent inoculation at other sites is the most frequent complication of vaccinia vaccination and accounts for approximately half of all complications of primary vaccination and revaccination (Tables 2,3). Inadvertent inoculation usually results from autoinoculation of vaccinia virus transferred from the site of vaccination. The most common sites involved are the face, eyelid, nose, mouth, genitalia, and rectum (Figure 4). Most lesions heal without specific therapy, but vaccinia immunoglobulin (VIG) can be useful for cases of ocular implantation (see Treatment for Vaccinia Vaccine Complications). However, if vaccinial keratitis is present, VIG is contraindicated because it might increase corneal scarring (51).
Erythematous or urticarial rashes can occur approximately 10 days after primary vaccination and can be confused with generalized vaccinia. However, the vaccinee is usually afebrile with this reaction, and the rash resolves spontaneously within 2--4 days. Rarely, bullous erythema multiforme (i.e., Stevens-Johnson syndrome) occurs (52).
Moderate to Severe Adverse Reactions. Moderate and severe complications of vaccinia vaccination include eczema vaccinatum, generalized vaccinia, progressive vaccinia, and postvaccinial encephalitis (Table 2). These complications are rare but occur >10 times more often among primary vaccinees than among revaccinees and are more frequent among infants than among older children and adults (53--55) (Table 3). A study of Israeli military recruits aged >18 years, who were vaccinated during 1991--1996, reported rates of the severe complications progressive vaccinia (i.e., vaccinia necrosum rate: 0/10,000 vaccinees) and postvaccinial encephalitis (rate: 0/10,000 vaccinees) similar to those reported in previous studies (56).
Eczema vaccinatum is a localized or systemic dissemination of vaccinia virus among persons who have eczema or a history of eczema or other chronic or exfoliative skin conditions (e.g., atopic dermatitis) (Figure 5). Usually, illness is mild and self-limited but can be severe or fatal. The most serious cases among vaccine recipients occur among primary vaccinees and are independent of the activity of the underlying eczema (57). Severe cases have been observed also after contact of recently vaccinated persons with persons who have active eczema or a history of eczema (see Contacts of Vaccinees) (Figure 6).
Generalized vaccinia is characterized by a vesicular rash of varying extent that can occur among persons without underlying illnesses (Figure 7). The rash is generally self-limited and requires minor or no therapy except among patients whose conditions might be toxic or who have serious underlying immunosuppressive illnesses (e.g., acquired immunodeficiency syndrome [AIDS]) (58).