Parvovirus B19 is implicates as a cause of human disease syndromes including mild illness with rash in children (erythema infectiosum), febrile illness with arthralgia or arthritis in adults, serious transient or chronic aplastic anemia in hematology, oncology, and immunocompromised patients, and fatal hydrops fetalis in unborn infants. A vaccine for immunization against B19 virus infection is urgently needed in certain of these situations. However, in others, immunoglobulin therapy may prove a more feasible and appropriate strategy. Current commercial immunoglobulin preparations are generally a good source of anti-B19 virus antibodies; however for effective therapy, extremely high doses are required. As yet there are no standards for plasma pools to be used for human parvovirus immunoglobulin therapy. The objective of this Phase I study is to establish these criteria. Use of gammaglobulin only from donors with high titer parvovirus neutralizing antibodies would greatly advance the therapeutic benefit of this approach. Unfortunately, the current assay for B19 virus neutralization is not amenable to screening large numbers of human sera for identification of appropriate plasma donors. Alternative methods are needed. We will develop a rapid and facile screening test that will correlate with the presence of high level B19 virus neutralizing antibodies in human sera. A variety of ELISA-formatted assays that qualitatively and quantitatively characterize anti-B19 virus antibodies in individual human sera will be developed and evaluated toward this end. The resulting surrogate neutralization test will then be applied, in Phase II work, toward the development and commercialization of a human parvovirus hyperimmune globulin product. Phase II work will employ the surrogate test to identify appropriate plasma donors possessing potent B19 virus neutralizing activity. Plasmapheresis of these individuals will yield plasma pools for hyperimmune globulin production. These anti-B19 virus immunoglobulin preparations will then be clinically evaluated in the treatment of pavoviremia and associated anemias.
