Annual and Interim Progress Report Summaries

Principal Investigator: Michel Nussenzweig

Project: Discovery & Characterization of bNAbs

Submitted April 1, 2012

In the first seven months of the award period the Nussenzweig laboratory has focused on collection of patient serum samples and characterization of their neutralizing activity (Objective 1). In addition, the Nussenzweig laboratory has developed new cloning methods for obtaining antibodies to quaternary epitopes (Objective 2). Preliminary experiments indicate that we have succeeded in applying the new methods to isolate antibodies that target novel epitopes. The Love laboratory has performed preliminary experiments on plasma cells (Objective 3) they have started to develop single cell methods to test for neutralizing activity (Objective 4). In addition, the Love laboratory has established proof of concept for antibody production in microbial strains (Objective 5). The work Ravetch laboratory has focused on characterizing the bNAbs isolated by Nussenzweig for their gp140 and FcR binding activities by SPR (Objective 6) and engineering the Fc of these antibodies for enhanced FcR binding and ADCC activity (Objective 7). We have completed activities 6.1.1 and are on track to complete the ADCC and ADCVI analysis of these antibodies (activity 6.1.2) and Fc glycan analysis (activity 6.2.2). They have also completed generating IgG1 Fc’s with selective RIIIA, RIIA and RIIB binding activities (activity 7.1.1) and are on track to complete the development of IgG1 Fc variants with enhanced ADCC activity (activity 7.2.1). The time course for completing the critical milestones of a human bNAb with ADCC activity (Objective 6) by mid-year 2 is on track and they are on track to complete the critical milestone of an Fc engineered bNAb with enhanced ADCC and/or ADCVI activity by the end of year 3.