SURROGATE ASSAY FOR B19 PARVOVIRUS SERUM NEUTRALIZATION

PARVOVIRUS B19 IS IMPLICATED AS A CAUSE OF MANY HUMAN DISEASE SYNDROMES. A VACCINE FOR IMMUNIZATION AGAINST B19 VIRUS INFECTION IS URGENTLY NEEDED IN CERTAIN OF THESE SITUATIONS, BUT, 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. THE 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. THIS PROJECT 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 SUCH ELISA-FORMATTED ASSAYS WILL BE DEVELOPED AND EVALUATED. THE RESULTING SURROGATE NEUTRALIZATION TEST WILL 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 PARVOVIREMIA AND ASSOCIATED ANEMIAS.