Commercial immune globulin, intravenous (IGIV) products contain anti-vaccinia antibodies

Abstract

Rationale Individuals with immune deficiency diseases may be at risk for vaccinia infection if widespread smallpox immunization programs are implemented in the U.S. for bioterrorism preparedness. Through inadvertent vaccination or contact with an infectious immunization site, immune deficient individuals could sustain morbidity or mortality from complications of vaccinia infection. Passively administered anti-vaccinia antibody-containing immune globulins can prevent or attenuate widespread vaccinia infection. Long-lasting antibody responses in blood or plasma donors could supply anti-vaccinia antibodies. In this study, we evaluated currently licensed IGIV products to determine whether they contain biologically active anti-vaccinia antibodies. Methods Eight licensed and two investigational IGIV products were tested in a vaccinia plaque reduction neutralization assay. Three lots of each product were tested and compared to a reference vaccinia immunoglobulin (VIG, positive control) and a commercially available 5% albumin product (negative control). Five of these lots were randomly selected to determine in vivo activity in SCID mice. Results All tested products contained anti-vaccinia antibodies when compared to the VIG standard in vitro. The mean antibody concentration that neutralized 50% of plaques was 0.413 mg/mL. In vivo, all IGIVs delayed mortality in vaccinia-inoculated SCID mice compared to untreated mice. Conclusions Commercial immune globulins contain anti-vaccinia antibody activity. Compared with VIG, the titers were lower, as would be expected. Since IGIV doses for immune deficient patients are four to eight fold higher than recommended VIG doses, use of IGIV may provide some protection for individuals with inherited or acquired immune deficiencies if they are exposed to vaccinia.