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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4364665?pdf=render |
| _version_ | 1818265351180255232 |
|---|---|
| author | Anton N Chikaev Anastasiya Yu Bakulina Ryan C Burdick Larisa I Karpenko Vinay K Pathak Alexander A Ilyichev |
| author_facet | Anton N Chikaev Anastasiya Yu Bakulina Ryan C Burdick Larisa I Karpenko Vinay K Pathak Alexander A Ilyichev |
| author_sort | Anton N Chikaev |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T19:49:25Z |
| format | Article |
| id | doaj.art-646a0a2d9c6c4962a59a63a2622fd2f7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:49:25Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-646a0a2d9c6c4962a59a63a2622fd2f72022-12-22T00:14:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012084710.1371/journal.pone.0120847Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01.Anton N ChikaevAnastasiya Yu BakulinaRyan C BurdickLarisa I KarpenkoVinay K PathakAlexander A IlyichevThe 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.http://europepmc.org/articles/PMC4364665?pdf=render |
| spellingShingle | Anton N Chikaev Anastasiya Yu Bakulina Ryan C Burdick Larisa I Karpenko Vinay K Pathak Alexander A Ilyichev Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01. PLoS ONE |
| title | Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01. |
| title_full | Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01. |
| title_fullStr | Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01. |
| title_full_unstemmed | Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01. |
| title_short | Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01. |
| title_sort | selection of peptide mimics of hiv 1 epitope recognized by neutralizing antibody vrc01 |
| url | http://europepmc.org/articles/PMC4364665?pdf=render |
| work_keys_str_mv | AT antonnchikaev selectionofpeptidemimicsofhiv1epitoperecognizedbyneutralizingantibodyvrc01 AT anastasiyayubakulina selectionofpeptidemimicsofhiv1epitoperecognizedbyneutralizingantibodyvrc01 AT ryancburdick selectionofpeptidemimicsofhiv1epitoperecognizedbyneutralizingantibodyvrc01 AT larisaikarpenko selectionofpeptidemimicsofhiv1epitoperecognizedbyneutralizingantibodyvrc01 AT vinaykpathak selectionofpeptidemimicsofhiv1epitoperecognizedbyneutralizingantibodyvrc01 AT alexanderailyichev selectionofpeptidemimicsofhiv1epitoperecognizedbyneutralizingantibodyvrc01 |