A significant proportion of anti-parvovirus B19 is considered to be neutralizing antibody. We continued to assess the levels of anti-B19 in products by utilizing a commercial EIA kit that has wells coated with a recombinant parvovirus B19 capsid protein, VP2. A semi-quantitative assay utilizing an international standard for anti-B19 IgG was set up and the sensitivity of the assay was ca. 30 mIU of anti-B19/mL. We found that among Factor VIII concentrates (AHF), the lower the purity, the higher the levels of anti-B19. Of intravenous immune globulin (IGIV) products, significant difference in anti-B19 levels was observed among products made by different manufacturers. The three manufacturers' anti-D immunoglobulin products, used by some pregnant women to prevent the hemolytic disease of the newborn, also had appreciable levels of anti-B19. The apparent viral safety of immunoglobulins with respect to B19 can be attributed to the presence of appreciable anti-B19 antibodies in the products. However, further monitoring the products is needed to determine whether the varying levels of anti-B19 are due to different manufacturing procedures, B19 NAT screening implemented by manufacturers, or other factors. In collaboration with scientists in OVRR, we continued to monitor levels of anti-measles antibodies in IGIV products. Varying neutralizing antibody levels were found among IGIV products. Further studies are needed to investigate why the levels vary and to evaluate the neutralizing capabilities by the IgG fragments and subclasses. The CBER anti-D immunoglobulin standard, which was formulated many years ago and was recently found HCV RNA positive by us, is nearly depleted. The current International Reference Preparation of anti-D immunoglobulin was also formulated many years ago and has been found HCV RNA positive too. Hence we began recently a collaborative study with Dr. Susan Thorpe of NIBSC to formulate a standard not only as a new CBER standard but also as a replacement standard for the WHO International Standard. We acquired two candidate materials from two U.S. manufacturers. Purity and potency assays have been carried out. The pilot experiments by blending different proportions of the two materials to achieve appropriate anti-D potency and IgG concentration in a freeze-dried formulation are in progress. Once it is formulated, a worldwide collaborative study will be set up to determine the consensus levels of this anti-D standard. We evaluated our HPLC method so that it can sensitively monitor the molecular integrity for immunoglobulin and albumin products. In collaboration with Dr. B Golding's group, we evaluated the molecular integrity for some lots of Vaccinia Immune Globulin (Human)and their derived IgG subclasses. The purity of several other pending hyperimmune globulin products have also been subjected to this analysis and found satisfactory.
