Antibody Fab‐Fc properties outperform titer in predictive models of SIV vaccine‐induced protection
2019
Abstract Characterizing the antigen‐binding and innate immune‐recruiting properties of the humoral response offers the chance to obtain deeper insights into mechanisms of protection than revealed by measuring only overall antibody
titer. Here, a high‐throughput, multiplexed Fab‐Fc Array was employed to profile
rhesus macaquesvaccinated with a gp120‐CD4 fusion protein in combination with different genetically encoded adjuvants, and subsequently subjected to multiple heterologous
simian immunodeficiency virus(SIV) challenges. Systems analyses modeling protection and adjuvant differences using Fab‐Fc Array measurements revealed a set of correlates yielding strong and robust predictive performance, while models based on measurements of response magnitude alone exhibited significantly inferior performance. At the same time, rendering Fab‐Fc
measurements mathematicallyindependent of
titerhad relatively little impact on predictive performance. Similar analyses for a distinct SIV vaccine study also showed that Fab‐Fc measurements performed significantly better than
titer. These results suggest that predictive modeling with measurements of antibody properties can provide detailed correlates with robust predictive power, suggest directions for vaccine improvement, and potentially enable discovery of mechanistic associations.
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