Core C: Humoral and Serological Core

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Project Summary A major goal of this U19 is to determine how PD-1 blockade affects human antibody responses against different viral antigens. Core C will fully interrogate serum antibody responses against a range of different viruses from donors undergoing PD-1 therapy in Projects 1 and 2. The Core will standardize assays, complete assays, and provide computational support for the analyses of complex serological datasets. We will offer standardized ELISA-based services that quantify antibodies specific for 5 viruses that are relevant for Projects 1 and 2. We will also assess quality of antibody responses through ELISAs that measure relative affinities and isotype diversity. It is possible that PD-1 blockade affects antiviral antibody responses in more subtle or global ways. To address this, we will complete serological screens to examine how PD-1 blockade affects antibody responses to a large fraction of known human viruses. For this, we will use a new array-based assay, termed ‘Viroscan’, that measures antibody binding to >400,000 non-redundant viral peptides. We will also offer services that intensively analyze antibody responses against a single virus (influenza). All humans are exposed to influenza virus in childhood and all adult encounters with influenza involve both the recall of memory B cells and the stimulation of de novo B cell responses. Our influenza virus antigenic analyses will allow us to determine if PD-1 blockade differentially regulates de novo versus memory antibody responses. Together, these standardized services will allow for the complete antigenic characterization of serum samples for Projects 1 and 2.