from Emerging Infectious Diseases

VACV immunoglobulin (VIG) is the only approved product currently available for treating complications of VACV vaccination. It is derived from the immunoglobulin fraction of plasma from persons who were immunized with VACV. The Red Cross initially obtained the product from the sera of hyperimmunized army recruits. The current supply of VIG is owned by the Department of Defense, which has provided some of this material to CDC for release in response to emergencies. VIG can be obtained from CDC to treat adverse reactions of VACV vaccine recipients, such as laboratory workers exposed to VACV or related Orthopoxviridae.

VIG is believed to be effective against certain complications of VACV vaccinations; it is recommended by the CDC's Advisory Committee on Immunization Practices for use in treating eczema vaccinatum, vaccinia necrosum, severe generalized VACV infections, VACV infections of the eyes (but not keratitis) or mouth, and VACV infections in the presence of other skin lesions such as burns, impetigo, varicella zoster, or poison ivy^[43]. No randomized controlled clinical trials have been performed to evaluate therapeutic efficacy in patients with VACV complications. However, a standard of care has developed based on data consisting of case series and anecdotal reports, as well as controlled data suggesting that VIG may modify VACV infection if administered concomitantly with vaccine.

Limited data from unblinded controlled studies support the efficacy of VIG in certain situations. In a trial conducted in Madras, India, 705 family contacts of 208 smallpox patients were randomized to receive smallpox vaccine or smallpox vaccine plus VIG as soon as possible after the index patient was admitted to the hospital. Smallpox developed in 5 of 326 contacts who received VIG compared with 21 of 379 controls, for a relative efficacy of 70% in preventing natural smallpox^[44] (p<0.05, calculated by the first author).

The potential for VIG to prevent postvaccine encephalitis when administered prophylactically with vaccine was studied among Dutch military recruits in a double-blinded, randomized, placebo-controlled trial^[45]. More than 106,000 recruits were randomized to receive VIG plus smallpox vaccine or placebo plus smallpox vaccine. Three cases of VACV-associated encephalitis occurred in the VIG group compared with 13 cases of encephalitis in the placebo group (p<0.05, calculated by author).

Published case series of patients with severe VACV vaccination complications treated with VIG suggest that VIG lowered case-fatality rates and shortened the course of disease^[20,46-52]. Other trials have used antiviral agents in an attempt to treat complications^[52-54], and these agents did not appear to have greater benefit than VIG. VIG is not considered to be effective in treating postvaccine encephalitis and is contraindicated for the treatment of vaccinal keratitis^[55].

The recommended therapeutic dosage of VIG is 0.6 mL/kg imtramuscularly, or 42 mL for a 70-kg adult; this dosage may be repeated as often as weekly. Such high intramuscular volume can be associated with trauma and possible nerve damage. Future development of VIG may include intravenous formulations to obviate these dose-related problems.

A more basic problem for the use of VIG is the availability of licensed product. The amount of VIG needed to respond to the adverse events associated with a large-scale vaccination program cannot be manufactured from the currently available human sera.