New IV agent combats complications from smallpox vaccine

Although smallpox was declared globally eradicated years ago, the threat of a bioterrorist reintroduction of the virus has compelled public health authorities to revive certain old products. Military personnel began taking the smallpox vaccine as a precautionary measure following the September 2001 terrorist attacks.

"Because the smallpox vaccine is made of live vaccinia virus and though it is a weakened version of the virus, it can occasionally cause severe adverse events," said Elfatih Abter, M.D., an infectious diseases specialist at Newark Beth Israel Medical Center in Newark, N.J.

In order to treat rare complications resulting from smallpox vaccination, Vaccinia Immune Globulin Intravenous (VIGIV, DVC, formerly DynPort Vaccine Co.) was recently approved by the Food & Drug Administration. The firm's research was part of a project spanning eight years with the Department of Defense's Joint Vaccine Acquisition Program (JVAP) Product Management Office. VIGIV is made from pooled plasma of donors who received booster immunizations with the licensed smallpox vaccine.

The approval of the new agent was based in part on prior results that found the levels of protective antibodies achieved during treatment adequate for treating complications of smallpox vaccination. In addition, clinical trials published in Clinical Infectious Diseases in 2004 have demonstrated the safety of the product. "When side effects were reported, they were mild to moderate and included headache, nausea, and upper respiratory tract infection," noted Abter.

Vaccinia immune globulin (VIG) was the brainchild of Henry Kempe, a pediatrician, who first developed the product in the 1950s. As a result of further research and his advocacy, a few years later essentially all serious smallpox vaccine-related side effects were treated with VIG, which at the time was administered via the intramuscular (IM) route.

The Centers for Disease Control & Prevention estimates that approximately 1,000 people for every one million individuals vaccinated experience serious reactions, such as a vaccinia rash or a toxic and allergic rash. Rarely, fewer than 50 individuals per one million people vaccinated have potentially life-threatening reactions. These include two conditions: progressive vaccinia, in which the vaccination site slowly enlarges and becomes necrotic, with similar lesions eventually forming on other parts of the body; and eczema vaccinatum, which is a serious rash caused by widespread infection of the skin in people with conditions such as atopic dermatitis. "These adverse reactions can be potentially fatal without VIG treatment, especially in individuals who have immunodeficiency such as with cancer or AIDS or who have a history of certain chronic skin conditions," Abter explained.

So what benefits does the new intravenous formulation of VIG offer over the old IM product? "VIGIV has advantages with regard to improved dosing, tolerability, and pharmacokinetic properties," said Abter. The intravenous administration of VIG would provide a more immediate protection against vaccinia, compared with a delayed onset of the IM route, where peak blood levels result three to seven days after administration.

Many licensed immune globulin intravenous products have been reported to be associated with renal dysfunction and acute renal failure. Therefore, the manufacturer recommends that in patients predisposed to acute renal failure, VIGIV should be administered at the minimum concentration available and at the minimum rate of infusion possible.

ecause antibodies present in immune globulin preparations may interfere with the immune response to live virus vaccines, administration of vaccines such as measles, mumps, and rubella should be deferred until about six months after the administration of VIGIV, Abter cautioned.

Even though VIGIV has FDA approval, the manufacturer currently does not intend to market it to the general population. "All of the product we have on hand and the doses we will be making in the future have been designated for the Department of Defense," stated Terry Irgens, president of DVC in El Segundo, Calif. But, if an emergency situation occurs within the general population, the FDA approval allows VIGIV to be made and used for individuals other than military personnel, she added.