A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability

mAbs, Journal Year: 2024, Volume and Issue: 16(1)

Published: Aug. 27, 2024

We previously described an in vitro single-chain fragment (scFv) library platform originally designed to generate antibodies with excellent developability properties. The design was based on the use of clinical as scaffolds into which replicated natural complementarity-determining regions purged sequence liabilities were inserted, and phage yeast display carry out antibody selection. In addition being developable, generated using our extremely diverse, most campaigns yielding sub-nanomolar binders. Here, we describe a advancement that incorporates Fab followed by antibody-binding (scFab) display. scFab single-gene format provides balanced expression light heavy chains, enhanced conversion IgG, thereby combining advantages scFvs Fabs. A meticulously engineered, quality-controlled created principles similar those used create scFv library. diverse panel binding scFabs, high efficiency isolated against two targets. This study highlights compatibility semi-synthetic design, offering efficient approach drug-like directly, facilitating their potential therapeutic candidates.

Language: Английский

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de NovoSequencing of Antibodies for Identification of Neutralizing Antibodies in Human Plasma Post SARS-CoV-2 Vaccination

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 15, 2024

Abstract We present a method for sequencing polyclonal IgG enriched from human plasma, employing combination of de novo sequencing, proteomics, bioinformatics, protein separation, and peptide separations. Our study analyzes single patient’s antibody response triggered by the Moderna Spikevax mRNA COVID-19 vaccine. From data natural to vaccination, we generated 12 recombinant antibodies. Six derived antibodies, including four with exhibited similar or higher binding affinities than original antibody. neutralization tests revealed that six antibodies possess neutralizing capabilities against target antigen. This research provides insights into while highlighting effectiveness potential our approach in generating robust affinity capabilities. proposed is an advancement characterizing directly investigating circulating pool without relying exclusively on B-cell repertoire population. crucial as analysis may not accurately represent Interestingly, large proportion (80 90%) sequences SARS-CoV-2 literature have been solely analysis. Therefore, ability offer different perspective gaining comprehensive understanding response. Significance Statement investigate targeting receptor domain using proteomics. The peripheral adequately cover all sequencing. overcomes this limitation top standard obtained distinct sequences, showcasing method’s potential. proteins generate traits comparable surpassing naturally occurring (pAbs). highlights similarities differences between populations blood B-cells, which future biologics development.

Language: Английский

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Phage Display in Cancer Research: Special Issue Editorial

Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 968 - 968

Published: June 17, 2024

Soon after its birth in 1985, following a short lag period [...]

Language: Английский

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Isolation of anti-Ancylostoma-secreted protein 5 (ASP5) antibody from a naïve antibody phage library

Journal of Immunological Methods, Journal Year: 2024, Volume and Issue: unknown, P. 113776 - 113776

Published: Nov. 1, 2024

Language: Английский

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Production and characterization of anti-porcine CXCL10 monoclonal antibodies

Cytokine, Journal Year: 2023, Volume and Issue: 174, P. 156449 - 156449

Published: Dec. 22, 2023

Language: Английский

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