Poster - #VH-12600 - Keywords: antibody, Fc, Fc effector function, vaccine, antibody therapeutic, systems serology, systems immunology

Association of clinical outcomes with Fc-dependent antibody effector functions using Systems Serology

Lenny Moise[1] and Shashi Jatiani[1]
[1]SeromYx Systems, Woburn, MA, USA

ABSTRACT:
Growing evidence linking humoral immune responses to the development of cancer and autoimmunity suggests that antibodies may serve as valuable biomarkers for predicting disease progression and therapeutic efficacy. The fragment crystallizable (Fc) region of antibodies carries structural determinants for Fc receptor and complement component 1q binding, which in turn trigger innate immune cell and complement functions critical to homeostasis, disease pathogenesis, and therapeutic response. However, the intricate and interconnected factors influencing antibody effector functions pose significant challenges in accurately predicting these functions and designing antibody therapeutics to achieve precise functional outcomes. A systems-based approach that integrates the Fc-dependent biophysical and functional properties of diverse antibody repertoires – correlating their multivariate profiles with specific disease outcomes or endotypes – could be instrumental in biomarker discovery. These insights, in turn, could guide the development of therapeutics capable of inducing the desired immune functions. To address this need, we have developed the Systems Serology platform, a suite of robust, high-throughput, and highly reproducible bead- and plate-based assays designed to analyze antigen-specific antibody responses in compliance with GCLP standards. We will present data showing three vaccine-induced humoral features that correlate with malaria protection in a controlled human infection model, as well as evidence that broad profiling of approved CD20 monoclonal antibodies reveals novel functional properties. The Systems Serology platform holds promise for uncovering Fc-dependent effector functions associated with clinical outcomes in a wide range of health conditions, paving the way for improved biomarker identification and therapeutic design.