Recombinant Hyperimmune Gammaglobulin for Primary Immunodeficiency

DESCRIPTION provided by applicant The Specific Aim of this SBIR direct to Phase II project is to develop natural repertoire recombinant intravenous immunoglobulin rIVIg andquot hyperimmunesandquot against common pathogens for patients with primary immune deficiency PID PID is a diverse family of congenital disorders including common variable immune deficiency CVID and X linked agammaglobulinemia XLA which are characterized by significantly reduced antibody titers Immunologists treat humoral PID with prophylactic intravenous immunoglobulin IVIg which is a pool of proteins isolated from the plasma of thousands of donors Still of patients suffer recurrent pneumonia and die from lung failure due to chronic lung disease Most PID patients with recurrent infections receive prophylactic antibiotics to address chronic infection Hyperimmunes are plasma derived gammaglobulins that are enriched for activity against a particular pathogen Unfortunately the nine FDA approved hyperimmunes do not address the pathogens that are most responsible for morbidity and mortality in PID patients Previously we developed GigaLink tm which uses microfluidics and multiplexed PCR to build massively polyclonal DNA libraries from antibody repertoires with native heavy and light chain immunoglobulin Ig pairing intact In our preliminary work we leveraged GigaLink tm to produce and characterize hyperimmune influenza rIVIg with andgt enriched binding activity In this SBIR direct to Phase II project we will add hyperimmunes for two more pathogens of critical importance to PID outcomes manufacture several test batches of rIVIg and perform toxicology pharmacokinetic and pathogen binding studies Though PID is the primary clinical indication these drugs could be used for other kinds of immunocompromised patients such as transplant recipients Finally our therapeutic approach will be useful to combat emerging pathogens i e for West Nile rapid response PUBLIC HEALTH RELEVANCE Intravenous immunoglobulin is used to treat many kinds of immune disorders and is currently derived from pools of sera from thousands of donors We are building new technology that will allow us to manufacture intravenous immunoglobulin with special activity against bacteria and viruses and with less reliance on donors