Compositions and methods for the treatment of immunodeficiency

摘要

The present invention relates to compositions and methods for the treatment of immunodeficiency (e.g., primary immunodeficiency disease). In particular, the invention provides human plasma immunoglobulin compositions containing select antibody titers specific for a plurality of respiratory pathogens, methods of identifying human donors and donor samples for use in the compositions, methods of manufacturing the compositions, and methods of utilizing the compositions (e.g., for prophylactic administration and/or therapeutic treatment (e.g., passive immunization (e.g., immune-prophylaxis))).

主权项

1. A method of producing a pooled plasma composition containing an elevated titer of respiratory syncytial virus (RSV) neutralizing antibodies and antibodies directed against one or more other respiratory pathogens comprising:
1) conducting a first assay to measure RSV neutralizing activity of plasma from individual human donors; 2) from donors demonstrating RSV neutralizing activity in the top 20% of the assayed population, purifying an immunoglobulin fraction and conducting an RSV titration curve measuring the RSV neutralizing titer of the immunoglobulin fraction, wherein donors with an immunoglobulin fraction RSV neutralizing titer of 1800 or above are categorized as high titer selected human donors; and 3) pooling plasma from 1000 or more donors including high titer selected human donors categorized according to step 2, wherein less than 50% of the donors are high titer selected human donors, such that the resultant pooled plasma comprises a titer of RSV neutralizing antibodies that is at least 3 times greater than the titer of RSV neutralizing antibodies in a control sample, and an antibody titer for one or more respiratory pathogens selected from parainfluenza virus 1, parainfluenza virus 2, coronavirus OC43 and coronavirus 229E that is at least 1.5 times greater than the antibody titer in the control sample, wherein the control sample is a mixture of plasma samples obtained from 1000 or more random human plasma donors.