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The rapid and highly parallel identification of antibodies with defined biological activities by SLISY
The covid pandemic has highlighted the need for rapid antibody development. Here, authors develop an approach called SLISY, which uses NGS with phage display to simultaneously assess millions of clones to rapidly isolate specific antibodies against SARS-CoV-2 and its evolving variants.
- Steve Lu
- , Austin K. Mattox
- & Kenneth W. Kinzler
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Article
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A conformation-specific nanobody targeting the nicotinamide mononucleotide-activated state of SARM1
SARM1 is a key player in axon degeneration. Here, the authors generate a nanobody, which specifically recognizes the NMN-bound state of SARM1 and helps resolve the SARM1 structure in an intermediate state of activation.
- Yun Nan Hou
- , Yang Cai
- & Yong Juan Zhao
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Efficient human-like antibody repertoire and hybridoma production in trans-chromosomic mice carrying megabase-sized human immunoglobulin loci
Trans-chromosomic (Tc) mice have helped the development of therapeutic antibodies, but chromosome instability limits its application. Here the authors develop a new line of Tc mice with full human Ig heavy and kappa loci integrated into the mouse artificial chromosome for stable passage, and confirm efficient generation of B cell responses and specific antibodies.
- Hiroyuki Satofuka
- , Satoshi Abe
- & Yasuhiro Kazuki
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Article
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A pandemic-enabled comparison of discovery platforms demonstrates a naïve antibody library can match the best immune-sourced antibodies
The most potent neutralizing antibodies are typically generated from convalescent patients and immunized animals. Here, the authors show it is possible to generate highly potent human neutralizing antibodies against the SARS-CoV-2 spike protein directly from a semisynthetic naïve antibody library.
- Fortunato Ferrara
- , M. Frank Erasmus
- & Andrew R. M. Bradbury
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Article
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A cell-free nanobody engineering platform rapidly generates SARS-CoV-2 neutralizing nanobodies
Faster, higher throughput antibody engineering methods are needed. Here the authors present CeVICA, a cell-free nanobody engineering platform using ribosome display and computational clustering analysis for in vitro selection; they use this to develop nanobodies against the RBD of SARS-CoV-2 spike protein.
- Xun Chen
- , Matteo Gentili
- & Aviv Regev
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Article
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Antibody toolkit reveals N-terminally ubiquitinated substrates of UBE2W
UBE2W catalyzes the ubiquitination of protein N-termini but its substrate spectrum is largely unknown. Here, the authors discover mAbs selective for peptides derived from N-terminally ubiquitinated proteins, solve the structure of a peptide-bound mAb and apply the mAbs to map endogenous UBE2W substrates by proteomics.
- Christopher W. Davies
- , Simon E. Vidal
- & James T. Koerber
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A conformation-selective monoclonal antibody against a small molecule-stabilised signalling-deficient form of TNF
TNF can be inhibited by small molecules that stabilize the TNF trimer in an asymmetric conformation. Here, the authors develop a monoclonal antibody that selectively binds this inactive form of TNF, enabling both target engagement assessment and structural characterization of TNF binding to TNF receptor 1.
- Daniel J. Lightwood
- , Rebecca J. Munro
- & Alastair D. G. Lawson
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Article
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Format chain exchange (FORCE) for high-throughput generation of bispecific antibodies in combinatorial binder-format matrices
Bispecific antibodies have been generated in many different formats and it is becoming clear that rational design alone cannot create optimal functionalities. Here the authors introduce the high throughput methodology, Format Chain Exchange (FORCE), to enable combinatorial generation of bispecific antibodies.
- Stefan Dengl
- , Klaus Mayer
- & Ulrich Brinkmann
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Article
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Rationally designed carbohydrate-occluded epitopes elicit HIV-1 Env-specific antibodies
Areas of HIV envelope (Env) that aren’t covered by glycans are potential targets for antibodies. Here, the authors computationally design small protein mimics of four such epitopes and show that they can induce Env binding antibodies in rabbits.
- Cheng Zhu
- , Elena Dukhovlinova
- & Nikolay V. Dokholyan
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Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity
Broadly neutralizing antibodies targeting HIV Env could potentially be utilized as therapeutics. Here, Steinhardt et al. engineer a trispecific antibody with specificity for the receptor-binding site, a conserved Env glycan patch and the Env membrane proximal region with nearly pan-isolate neutralization breadth and high potency.
- James J. Steinhardt
- , Javier Guenaga
- & Yuxing Li
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Article
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Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models
Selenoprotein P is secreted by the liver and when present in excess it promotes development of type 2 diabetes. Here the authors develop neutralizing antibodies to target human and mouse selenoprotein P, and show that they improve insulin secretion and glucose tolerance in mouse models.
- Yuichiro Mita
- , Kaho Nakayama
- & Yoshiro Saito
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A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve
A major goal of vaccine design is to protect against a broad range of pathogen strains. Here the authors isolate a new broadly neutralizing antibody against influenza haemagglutinin from human memory B cells, and identify mutations that increase and broaden the neutralization towards H5 HA subtype.
- Ying Fu
- , Zhen Zhang
- & Wayne A. Marasco
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Efficient generation of monoclonal antibodies against peptide in the context of MHCII using magnetic enrichment
Generating antibodies specific for the peptide–MHCII complexes has been challenging, with only a handful made to date. Here, the authors develop a more efficient approach to generate these antibodies, and demonstrate their potential in research and therapeutic applications.
- Justin A. Spanier
- , Daniel R. Frederick
- & Brian T. Fife
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Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production
Antigen receptors on memory B cells enhance their signaling strength by recruiting the cytosolic Grb2 adaptor to their ITT phosphorylation motifs. Here the authors show that inactivating the ITT motif of mouse mIgG1 impairs IgG1 production and T-cell independent reactivation of memory B cells.
- Johannes Lutz
- , Kai Dittmann
- & Niklas Engels
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A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins
There is no licensed vaccine or therapeutic for dengue virus (DENV) infection. Here, the authors show that a highly potent human monoclonal antibody binds to DENV particles in an unusual and very effective way by interacting with three viral envelope proteins.
- Guntur Fibriansah
- , Joanne L. Tan
- & Shee-Mei Lok
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Article
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Creation of a gated antibody as a conditionally functional synthetic protein
The ability to control antibody binding could have important medical implications. Here, the authors present a method to engineer phosphatase-controllable antibodies that bind to a specific recognition site in the presence of two biomarker inputs.
- Smita B. Gunnoo
- , Helene M. Finney
- & Benjamin G. Davis
SpyMask enables combinatorial assembly of bispecific binders