This application note presents a groundbreaking approach to addressing the challenges of identifying conserved, neutralizing epitopes for effective antibody therapeutics against emerging coronavirus variants. Leveraging multiplexed antigen screening and single-cell immune profiling technology, over 9,000 fully human CoV-specific antibodies were identified, paving the way for potential pan-coronavirus vaccine candidates. The manuscript also introduces Twist High Throughput Antibody (HT IgG) production, a gene-to-protein workflow designed to overcome the bottleneck of antibody synthesis, expression, and purification at scale, enabling rapid screening of hundreds or thousands of leads for biophysical and pharmacokinetic properties.  

Twist Express Antibodies relieve the traditional research bottleneck of full-length antibody expression. Twist provides a seamless experience by leveraging Express Genes oligo synthesis platform to produce NGS sequence-verified clonal genes ready for transfection and expression in mammalian cells, all under one roof. Our automated production line is capable of producing 10s to 1000s of IgG and VHH antibodies in as few as 2 weeks.  

Structure-based machine learning was leveraged to design predicted antibody binders against the GPCR target C5aR1. The CDR sequences of these predicted binders were then used to construct a de-novo phage-display library. Twist’s oligo-synthesis platform enabled fabrication of a highly diverse CDR-shuffle library with excellent variant representation and with no unwanted bias or motifs. Following panning, several high-affinity leads were identified that functionally blocked C5aR1 signaling in cellular assays.  This symposium was part of the event Antibody Engineering & Therapeutics Europe 2024.