Antibody Fab‐Fc properties outperform titer in predictive models of SIV vaccine‐induced protection
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44320_2019_Article_BFMSB188747.pdf
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Author(s)
Pittala, Srivamshi
Bagley, Kenneth
Schwartz, Jennifer A.
Brown, Eric P.
Weiner, Joshua A.
Prado, Ilia J.
Zhang, Wenlei
Xu, Rong
Ota‐Setlik, Ayuko
Pal, Ranajit
Date Issued
May 2, 2019
Journal
molecular systems biology
Publisher
Nature Publishing Group UK
Citation
Molecular Systems Biology. 2019 May 02;15(5):MSB188747
Version
Final published version
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 macaques vaccinated 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 mathematically independent of titer had 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.
MIT Department
Ragon Institute of MGH, MIT and Harvard
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.15252/msb.20188747
