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

PloS One
Anton N ChikaevAlexander A Ilyichev

Abstract

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. ...Continue Reading

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Citations

Sep 5, 2019·Vaccines·Behazine CombadièreVincent Vieillard
May 20, 2020·International Journal of Peptide Research and Therapeutics·Garima Agarwal, Reema Gabrani
Feb 19, 2021·Experimental Biology and Medicine·Nneka Pu KorieOsbourne Quaye
Sep 28, 2020·Virology·Lindsay WieczorekVenigalla Rao

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Methods Mentioned

BETA
targeted mutations
phage display
ELISA
Assay
dot-blot
dot blot
X-ray

Software Mentioned

PyMOL
MimoDB
Pepitope
BioEdit
pdMap
Pepitope server

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