Medical Management of Adverse Reactions to Vaccinia Virus Vaccination

The vaccinia virus vaccines (smallpox vaccine) are generally safe and effective, but some people do experience side effects and adverse reactions. Vaccinia immune globulin intravenous (VIGIV) is recommended as the first line of therapy for treatment of adverse reactions resulting from continued vaccinia virus replication after vaccination using ACAM2000® or APSV. Antivirals may be considered as a secondary treatment after consultation with CDC. Clinicians who need assistance with the diagnosis and management of patients with suspected complications of vaccinia virus vaccination should consult with their state/local public health department. CDC will also provide consultation if requested. Contact CDC medical staff by calling the CDC Emergency Operations Center at 770-488-7100.

Vaccinia Immune Globulin Intravenous (Human) (VIGIV)

VIGIV [PDF – 18 pages] has been used safely and effectively in smallpox vaccinated individuals to treat adverse reactions that are secondary to continued vaccinia virus replication after vaccination. VIGIV is licensed by FDA for the treatment of following complications resulting from smallpox vaccination:

• Eczema vaccinatum
• Progressive vaccinia
• Severe cases of generalized vaccinia
• Vaccinia infections in individuals who have skin conditions such as burns, impetigo, varicella-zoster, or poison ivy; or in individuals who have eczematous skin lesions because of either the activity or extensiveness of such lesions
• Aberrant infections induced by vaccinia virus that include its accidental implantation in eyes (except in cases of isolated keratitis), mouth, or other areas where vaccinia infection would constitute a special hazard

VIGIV is not indicated for the treatment of isolated vaccinia keratitis or postvaccinial encephalitis. It is not indicated for the treatment of smallpox disease. VIGIV is not commercially available but can be made available through the Strategic National Stockpile (SNS) for the treatment of smallpox vaccine complications in patients with serious clinical manifestations.

Antivirals

If treatment with VIGIV alone is inadequate or if VIGIV is not readily available, the following three antivirals may be considered, based on clinical determination for antiviral treatment. No antivirals are currently approved by the FDA for treatment of complications which might arise from vaccinia vaccination, but some may be used under expanded access investigational new drug (IND) protocols.

• Tecovirimat (also referred to as ST-246 or its brand name Tpoxx) has demonstrated in vitro activity against various orthopoxviruses (e.g., variola, vaccinia, and monkeypox viruses) and shown effectiveness in animal challenge studies using related orthopoxviruses. This antiviral is FDA-approved for the treatment of variola virus infections (smallpox) and could be used under an expanded access investigational new drug (IND) protocol for the treatment of adverse reactions secondary to continued vaccinia virus replication after smallpox vaccination. Tecovirimat has been used in a small number of individuals to date for the treatment of severe adverse events resulting from vaccinia virus vaccination, and effectiveness data in humans is limited. Tecovirimat is known to have fewer side effects than cidofovir.
• Brincidofovir (TEMBEXA) has demonstrated in vitro activity against various orthopoxviruses (e.g., variola, vaccinia, and monkeypox viruses) and shown effectiveness in animal challenge studies using related orthopoxviruses. This antiviral is FDA-approved for the treatment of variola virus infections (smallpox). Brincidofovir may have fewer adverse events than cidofovir (which is FDA-approved for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome). Patients being treated with cidofovir have experienced serious renal toxicity and other adverse events that have not been observed in patients being treated with brincidofovir.
• Cidofovir has shown effectiveness in animal and in vitro studies; however, there are limited data on the effectiveness in the treatment of vaccinia-related complications in humans. There are also limited data on the effectiveness in treatment of smallpox disease. It is not FDA-approved for the treatment of orthopoxvirus infections, but could be used under an expanded access IND protocol for the treatment of complications which might arise from vaccinia virus vaccination.

Currently, tecovirimat and cidofovir are stockpiled by the SNS and would be made available under the appropriate regulatory mechanism. However, brincidofovir is not available through the SNS.

Obtaining VIGIV and Antivirals

Clinicians who need clinical consultation for patients experiencing a severe or unexpected adverse reaction following vaccinia virus vaccination, or who would like to request release of VIGIV or antivirals, should contact their state/local health department or the CDC Emergency Operations Center at 770-488-7100. If it is determined that treatment of vaccinia virus vaccine adverse reactions requires VIGIV or antivirals, the CDC Smallpox Vaccine Adverse Events Clinical Consultation Team will coordinate shipment with the Strategic National Stockpile.

Health care providers at military medical facilities (or civilian providers treating a U.S. Department of Defense healthcare beneficiary) should call the Defense Health Agency’s 24/7 Immunization Healthcare Support Center at 877-GETVACC (877-438-8222) and select option #1.