Phage display as a tool for identifying HIV-1 broadly neutralizing antibodies.

A N Chikaev,A P Rudometov,Yu A Merkulyeva,L I Karpenko

doi:10.18699/vj21.063

Abstract

Combinatorial biology methods offer a good solution for targeting interactions of specif ic molecules by a high-throughput screening and are widely used for drug development, diagnostics, identif ication of novel monoclonal antibodies, search for linear peptide mimetics of discontinuous epitopes for the development of immunogens or vaccine components. Among all currently available techniques, phage display remains one of the most popular approaches. Despite being a fairly old method, phage display is still widely used for studying protein-protein, peptide-protein and DNA-protein interactions due to its relative simplicity and versatility. Phage display allows highly representative libraries of peptides, proteins or their fragments to be created. Each phage particle in a library displays peptides or proteins fused to its coat protein and simultaneously carries the DNA sequence encoding the displayed peptide/protein in its genome. The biopanning procedure allows isolation of specif ic clones for almost any target, and due to the physical link between the genotype and the phenotype of recombinant phage particles it is possible to determine the structure of selected molecules. Phage display technology continues to play an important role in HIV research. A major obstacle to the development of an effective HIV vaccine is an extensive genetic and antigenic variability of the virus. According to recent data, in order to provide protection against HIV infection, the so-called broadly neutralizing antibodies that are cross-reactive against multiple viral strains of HIV must be induced, which makes the identif ication of such antibodies a key area of HIV vaccinology. In this review, we discuss the use of phage display as a tool for identif ication of HIV-specif ic antibodies with broad neutralizing activity. We provide an outline of phage display technology, brief ly describe the design of antibody phage libraries and the affinity selection procedure, and discuss the biology of HIV-1-specif ic broadly neutralizing antibodies. Finally, we summarize the studies aimed at identif ication of broadly neutralizing antibodies using various types of phage libraries.

Highlights

Phage display was first described in 1985 by George Smith and Gregory Winter, who were awarded the 2018 Nobel Prize in Chemistry for this discovery
Known HIV-1 sites of vulnerabilities to broadly neutralizing antibodies are indicated: gp120 binding site (CD4bs); V1/V2 glycan apex, loops V3 glycan loop of gp120 (V1/V2, V3); CD4-induced CCR5/CXCR4 binding site which is exposed following CD4 binding (CD4i); gp120/gp41 interface; membraneproximal external region of gp41 (MPER); gp41 N-terminal fusion peptide, which anchors to the host cell membrane
Mil ler’s research group (Miller et al, 2005). They used B-cells from the bone marrow of an HIV-negative patient for naive scFv phage library construction and subsequent identification of human monoclonal antibodies specific to the gp41 N-ter minal region (NHR)

Summary

Introduction

Phage display was first described in 1985 by George Smith and Gregory Winter, who were awarded the 2018 Nobel Prize in Chemistry for this discovery. Применение фагового дисплея для поиска ВИЧ-1-нейтрализующих антител Тема настоящего обзора – применение фагового дисплея в качестве инструмента для поиска ВИЧ-1-нейтрализующих антител широкого спектра действия.

Results

Conclusion