Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01

The ability to induce anti-HIV-1 antibodies that can neutralize a broad spectrum of viral isolates from different subtypes seems to be a key requirement for development of an effective HIV-1 vaccine. The epitopes recognized by the most potent broadly neutralizing antibodies that have been characteri...

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Bibliographic Details
Published in:PloS one 2015-03, Vol.10 (3), p.e0120847-e0120847
Main Authors: Chikaev, Anton N, Bakulina, Anastasiya Yu, Burdick, Ryan C, Karpenko, Larisa I, Pathak, Vinay K, Ilyichev, Alexander A
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
AIDS vaccines
Amino Acid Sequence
Analysis
Antibodies, Neutralizing - immunology
Antigenic determinants
Antiviral agents
Binding
CD4 antigen
Computer applications
Development and progression
Display devices
Drug resistance
Epitopes
Epitopes - chemistry
Epitopes - immunology
Glycoprotein gp120
HIV
HIV Envelope Protein gp120 - chemistry
HIV Envelope Protein gp120 - metabolism
HIV-1 - immunology
Homology
Human immunodeficiency virus
Infectivity
Inhibition
Molecular Docking Simulation
Monoclonal antibodies
Mutation
Neutralization
Neutralizing
Peptide libraries
Peptide Library
Peptides
Peptidomimetics - chemistry
Peptidomimetics - immunology
Peptidomimetics - metabolism
Phage display
Phages
Protein Conformation
Sequence Alignment
Vaccines
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Summary:The ability to induce anti-HIV-1 antibodies that can neutralize a broad spectrum of viral isolates from different subtypes seems to be a key requirement for development of an effective HIV-1 vaccine. The epitopes recognized by the most potent broadly neutralizing antibodies that have been characterized are largely discontinuous. Mimetics of such conformational epitopes could be potentially used as components of a synthetic immunogen that can elicit neutralizing antibodies. Here we used phage display technology to identify peptide motifs that mimic the epitope recognized by monoclonal antibody VRC01, which is able to neutralize up to 91% of circulating primary isolates. Three rounds of biopanning were performed against 2 different phage peptide libraries for this purpose. The binding specificity of selected phage clones to monoclonal antibody VRC01 was estimated using dot blot analysis. The putative peptide mimics exposed on the surface of selected phages were analyzed for conformational and linear homology to the surface of HIV-1 gp120 fragment using computational analysis. Corresponding peptides were synthesized and checked for their ability to interfere with neutralization activity of VRC01 in a competitive inhibition assay. One of the most common peptides selected from 12-mer phage library was found to partially mimic a CD4-binding loop fragment, whereas none of the circular C7C-mer peptides was able to mimic any HIV-1 domains. However, peptides identified from both the 12-mer and C7C-mer peptide libraries showed rescue of HIV-1 infectivity in the competitive inhibition assay. The identification of epitope mimics may lead to novel immunogens capable of inducing broadly reactive neutralizing antibodies.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0120847