Novel Hiv Neutralizing Antibodies Selected from Phage Display Libraries

Antibodies ◽  
2004 ◽  
pp. 105-117 ◽  
Author(s):  
Maxime Moulard ◽  
Mei-Yun Zhang ◽  
Dimiter S. Dimitrov
Keyword(s):  
Phage Display ◽  
Neutralizing Antibodies ◽  
Phage Display Libraries

scholarly journals Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yongbing Pan ◽  
Jianhui Du ◽  
Jia Liu ◽  
Hai Wu ◽  
Fang Gui ◽  
...  
Keyword(s):  
Phage Display ◽  
Neutralizing Antibodies ◽  
Variable Region ◽  
Neutralizing Antibody ◽  
Chain Gene ◽  
Prophylactic Efficacy ◽  
Heavy Chains ◽  
Effective Interventions ◽  
Phage Display Libraries

AbstractAs the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

scholarly journals Selection of Peptides Targeting Helix 31 of Bacterial 16S Ribosomal RNA by Screening M13 Phage-Display Libraries

Molecules ◽  
2011 ◽  
Vol 16 (2) ◽  
pp. 1211-1239 ◽  
Author(s):  
Tek N. Lamichhane ◽  
N. Dinuka Abeydeera ◽  
Anne-Cécile E. Duc ◽  
Philip R. Cunningham ◽  
Christine S. Chow
Keyword(s):  
Phage Display ◽  
Ribosomal Rna ◽  
16S Ribosomal Rna ◽  
Phage Display Libraries ◽  
M13 Phage ◽  
Selection Of

scholarly journals Peptides derived from phage display libraries as potential neutralizers of Shiga toxin-induced cytotoxicity in vitro and in vivo

2014 ◽  
Vol 116 (5) ◽  
pp. 1322-1333 ◽  
Author(s):  
R.A. Bernedo-Navarro ◽  
M.M. Miyachiro ◽  
M.J. da Silva ◽  
C.F. Reis ◽  
R.A. Conceição ◽  
...  
Keyword(s):  
Phage Display ◽  
Shiga Toxin ◽  
Phage Display Libraries

scholarly journals Development of Anti-Infectives Using Phage Display: Biological Agents against Bacteria, Viruses, and Parasites

2012 ◽  
Vol 56 (9) ◽  
pp. 4569-4582 ◽  
Author(s):  
Johnny X. Huang ◽  
Sharon L. Bishop-Hurley ◽  
Matthew A. Cooper
Keyword(s):  
Phage Display ◽  
Significant Contribution ◽  
Biological Agents ◽  
Preclinical Development ◽  
Phage Display Technology ◽  
Whole Cells ◽  
Drug Candidates ◽  
Phage Display Libraries ◽  
Wide Range ◽  
Display Technology

ABSTRACTThe vast majority of anti-infective therapeutics on the market or in development are small molecules; however, there is now a nascent pipeline of biological agents in development. Until recently, phage display technologies were used mainly to produce monoclonal antibodies (MAbs) targeted against cancer or inflammatory disease targets. Patent disputes impeded broad use of these methods and contributed to the dearth of candidates in the clinic during the 1990s. Today, however, phage display is recognized as a powerful tool for selecting novel peptides and antibodies that can bind to a wide range of antigens, ranging from whole cells to proteins and lipid targets. In this review, we highlight research that exploits phage display technology as a means of discovering novel therapeutics against infectious diseases, with a focus on antimicrobial peptides and antibodies in clinical or preclinical development. We discuss the different strategies and methods used to derive, select, and develop anti-infectives from phage display libraries and then highlight case studies of drug candidates in the process of development and commercialization. Advances in screening, manufacturing, and humanization technologies now mean that phage display can make a significant contribution in the fight against clinically important pathogens.

scholarly journals Generation of Lamprey Monoclonal Antibodies (Lampribodies) Using the Phage Display System

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 868 ◽  
Author(s):  
Khan M. A. Hassan ◽  
John D. Hansen ◽  
Brantley R. Herrin ◽  
Chris T. Amemiya
Keyword(s):  
Monoclonal Antibodies ◽  
Phage Display ◽  
Genomic Rearrangements ◽  
Filamentous Phage ◽  
Human Cell Lines ◽  
Display System ◽  
Phage Display Libraries ◽  
Humoral Antibodies ◽  
Leucine Rich Repeats ◽  
Lymphocyte Receptors

The variable lymphocyte receptors (VLRs) consist of leucine rich repeats (LRRs) and comprise the humoral antibodies produced by lampreys and hagfishes. The diversity of the molecules is generated by stepwise genomic rearrangements of LRR cassettes dispersed throughout the VLRB locus. Previously, target-specific monovalent VLRB antibodies were isolated from sea lamprey larvae after immunization with model antigens. Further, the cloned VLR cDNAs from activated lamprey leukocytes were transfected into human cell lines or yeast to select best binders. Here, we expand on the overall utility of the VLRB technology by introducing it into a filamentous phage display system. We first tested the efficacy of isolating phage into which known VLRB molecules were cloned after a series of dilutions. These experiments showed that targeted VLRB clones could easily be recovered even after extensive dilutions (1 to 109). We further utilized the system to isolate target-specific “lampribodies” from phage display libraries from immunized animals and observed an amplification of binders with relative high affinities by competitive binding. The lampribodies can be individually purified and ostensibly utilized for applications for which conventional monoclonal antibodies are employed.

scholarly journals Extremely potent monoclonal antibodies neutralize Omicron and other SARS-CoV-2 variants

2022 ◽  
Author(s):  
Zhaochun Chen ◽  
Peng Zhang ◽  
Yumiko Matsuoka ◽  
Yaroslav Tsybovsky ◽  
Kamille West ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Structural Basis ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Phage Display Libraries ◽  
Antibody Phage ◽  
Antibody Phage Display ◽  
Early Isolate

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a devastating global health, social and economic crisis. The RNA nature and broad circulation of this virus facilitate the accumulation of mutations, leading to the continuous emergence of variants of concern with increased transmissibility or pathogenicity1. This poses a major challenge to the effectiveness of current vaccines and therapeutic antibodies1,2. Thus, there is an urgent need for effective therapeutic and preventive measures with a broad spectrum of action, especially against variants with an unparalleled number of mutations such as the recently emerged Omicron variant, which is rapidly spreading across the globe3. Here, we used combinatorial antibody phage-display libraries from convalescent COVID-19 patients to generate monoclonal antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein with ultrapotent neutralizing activity. One such antibody, NE12, neutralizes an early isolate, the WA-1 strain, as well as the Alpha and Delta variants with half-maximal inhibitory concentrations at picomolar level. A second antibody, NA8, has an unusual breadth of neutralization, with picomolar activity against both the Beta and Omicron variants. The prophylactic and therapeutic efficacy of NE12 and NA8 was confirmed in preclinical studies in the golden Syrian hamster model. Analysis by cryo-EM illustrated the structural basis for the neutralization properties of NE12 and NA8. Potent and broadly neutralizing antibodies against conserved regions of the SARS-CoV-2 spike protein may play a key role against future variants of concern that evade immune control.

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