Phage and Ribosome Display for Antibody Discovery and Optimization

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 4367

Special Issue Editor


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Guest Editor
Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, Jacksonville, FL 32224, USA
Interests: phage and ribosome display; antibody discovery and engineering; computational modeling; antibody humanization and affinity maturation; optimization; diagnostics and therapeutics
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Special Issue Information

Dear Colleagues,

Therapeutic antibodies have become a major driving force for the biopharmaceutical industry; therefore, the discovery and development of safe and efficacious antibody leads have become competitive processes. Phage and ribosome display are ideal tools for the generation of such molecules and have already delivered an approved drug as well as a multitude of clinical candidates. Large libraries (up to 1015) can be rapidly constructed, antibodies selected, and sequence space extensively explored by targeted mutagenesis techniques or by random mutagenesis throughout the antibody sequence. Such approaches in ribosome display systems lead antibodies derived from phage display or from immunized animals have been improved more than 1000-fold in potency within the past 6 months. In addition, this approach (i) provides a rapid route for antibody humanization constraining the content of original mouse sequences in the final antibodies to the most hypervariable of the complementarity-determining regions (CDRs) using CDR grafting platform, (ii) generates several humanized versions with different sequences at the same time, (iii) results in affinities as high as or higher than the affinity of the original antibody, and (iv) retains the original antibody specificity and eliminates its immunogenicity in humans. It also allows screening for antibody expression, solubility, and stability for later therapeutic development.

This Special Issue of Antibodies will consider any submission associated with phage and ribosome display, whether it be its use for discovering novel antibodies, the development of new phage and ribosome display techniques, optimization, humanization and affinity maturation approaches, or its utilization in novel applications in diagnostics and therapeutics.

Prof. Dr. Adinarayana Kunamneni
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • phage and ribosome display
  • display technologies
  • recombinant antibody formats
  • combinatorial libraries
  • biopanning
  • selection
  • lead characterization
  • humanization and affinity maturation
  • optimization
  • physiochemical properties
  • macromolecular mechanisms and interactions
  • diagnostics
  • therapeutics
  • other applications

Published Papers (1 paper)

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Research

14 pages, 2186 KiB  
Article
Highly Specific Monoclonal Antibody Targeting the Botulinum Neurotoxin Type E Exposed SNAP-25 Neoepitope
by Adva Mechaly, Eran Diamant, Ron Alcalay, Alon Ben David, Eyal Dor, Amram Torgeman, Ada Barnea, Meni Girshengorn, Lilach Levin, Eyal Epstein, Ariel Tennenhouse, Sarel J. Fleishman, Ran Zichel and Ohad Mazor
Antibodies 2022, 11(1), 21; https://doi.org/10.3390/antib11010021 - 16 Mar 2022
Cited by 5 | Viewed by 3797
Abstract
Botulinum neurotoxin type E (BoNT/E), the fastest acting toxin of all BoNTs, cleaves the 25 kDa synaptosomal-associated protein (SNAP-25) in motor neurons, leading to flaccid paralysis. The specific detection and quantification of the BoNT/E-cleaved SNAP-25 neoepitope can facilitate the development of cell-based assays [...] Read more.
Botulinum neurotoxin type E (BoNT/E), the fastest acting toxin of all BoNTs, cleaves the 25 kDa synaptosomal-associated protein (SNAP-25) in motor neurons, leading to flaccid paralysis. The specific detection and quantification of the BoNT/E-cleaved SNAP-25 neoepitope can facilitate the development of cell-based assays for the characterization of anti-BoNT/E antibody preparations. In order to isolate highly specific monoclonal antibodies suitable for the in vitro immuno-detection of the exposed neoepitope, mice and rabbits were immunized with an eight amino acid peptide composed of the C-terminus of the cleaved SNAP-25. The immunized rabbits developed a specific and robust polyclonal antibody response, whereas the immunized mice mostly demonstrated a weak antibody response that could not discriminate between the two forms of SNAP-25. An immune scFv phage-display library was constructed from the immunized rabbits and a panel of antibodies was isolated. The sequence alignment of the isolated clones revealed high similarity between both heavy and light chains with exceptionally short HCDR3 sequences. A chimeric scFv-Fc antibody was further expressed and characterized, exhibiting a selective, ultra-high affinity (pM) towards the SNAP-25 neoepitope. Moreover, this antibody enabled the sensitive detection of cleaved SNAP-25 in BoNT/E treated SiMa cells with no cross reactivity with the intact SNAP-25. Thus, by applying an immunization and selection procedure, we have isolated a novel, specific and high-affinity antibody against the BoNT/E-derived SNAP-25 neoepitope. This novel antibody can be applied in in vitro assays that determine the potency of antitoxin preparations and reduce the use of laboratory animals for these purposes. Full article
(This article belongs to the Special Issue Phage and Ribosome Display for Antibody Discovery and Optimization)
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