Cargando…

Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display

We have developed a peptide display platform based on VLPs of the RNA bacteriophage MS2 that combines the high immunogenicity of VLP display with affinity selection capabilities. Random peptides can be displayed on the VLP surface by genetically inserting sequences into a surface-exposed loop of the...

Descripción completa

Detalles Bibliográficos
Autores principales: Crossey, Erin, Frietze, Kathryn, Narum, David L., Peabody, David S., Chackerian, Bryce
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493041/
https://www.ncbi.nlm.nih.gov/pubmed/26147502
http://dx.doi.org/10.1371/journal.pone.0132560
_version_ 1782379851645190144
author Crossey, Erin
Frietze, Kathryn
Narum, David L.
Peabody, David S.
Chackerian, Bryce
author_facet Crossey, Erin
Frietze, Kathryn
Narum, David L.
Peabody, David S.
Chackerian, Bryce
author_sort Crossey, Erin
collection PubMed
description We have developed a peptide display platform based on VLPs of the RNA bacteriophage MS2 that combines the high immunogenicity of VLP display with affinity selection capabilities. Random peptides can be displayed on the VLP surface by genetically inserting sequences into a surface-exposed loop of the viral coat protein. VLP-displayed peptides can then be isolated by selection using antibodies, and the VLP selectants can then be used directly as immunogens. Here, we investigated the ability of this platform to identify mimotopes of a highly conserved conformational epitope present on the Plasmodium falciparum blood-stage protein AMA1. Using 4G2, a monoclonal antibody that binds to this epitope and is a potent inhibitor of erythrocyte invasion, we screened three different VLP-peptide libraries and identified specific VLPs that bound strongly to the selecting mAb. We then tested the ability of a handful of selected VLPs to elicit anti-AMA1 antibody responses in mice. Most of the selected VLPs failed to reliably elicit AMA1 specific antibodies. However, one VLP consistently induced antibodies that cross-reacted with AMA1. Surprisingly, this VLP bound to 4G2 more weakly than the other selectants we identified. Taken together, these data demonstrate that VLP-peptide display can identify immunogenic mimics of a complex conformational epitope and illustrate the promise and challenges of this approach.
format Online
Article
Text
id pubmed-4493041
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-44930412015-07-15 Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display Crossey, Erin Frietze, Kathryn Narum, David L. Peabody, David S. Chackerian, Bryce PLoS One Research Article We have developed a peptide display platform based on VLPs of the RNA bacteriophage MS2 that combines the high immunogenicity of VLP display with affinity selection capabilities. Random peptides can be displayed on the VLP surface by genetically inserting sequences into a surface-exposed loop of the viral coat protein. VLP-displayed peptides can then be isolated by selection using antibodies, and the VLP selectants can then be used directly as immunogens. Here, we investigated the ability of this platform to identify mimotopes of a highly conserved conformational epitope present on the Plasmodium falciparum blood-stage protein AMA1. Using 4G2, a monoclonal antibody that binds to this epitope and is a potent inhibitor of erythrocyte invasion, we screened three different VLP-peptide libraries and identified specific VLPs that bound strongly to the selecting mAb. We then tested the ability of a handful of selected VLPs to elicit anti-AMA1 antibody responses in mice. Most of the selected VLPs failed to reliably elicit AMA1 specific antibodies. However, one VLP consistently induced antibodies that cross-reacted with AMA1. Surprisingly, this VLP bound to 4G2 more weakly than the other selectants we identified. Taken together, these data demonstrate that VLP-peptide display can identify immunogenic mimics of a complex conformational epitope and illustrate the promise and challenges of this approach. Public Library of Science 2015-07-06 /pmc/articles/PMC4493041/ /pubmed/26147502 http://dx.doi.org/10.1371/journal.pone.0132560 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Crossey, Erin
Frietze, Kathryn
Narum, David L.
Peabody, David S.
Chackerian, Bryce
Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display
title Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display
title_full Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display
title_fullStr Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display
title_full_unstemmed Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display
title_short Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display
title_sort identification of an immunogenic mimic of a conserved epitope on the plasmodium falciparum blood stage antigen ama1 using virus-like particle (vlp) peptide display
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493041/
https://www.ncbi.nlm.nih.gov/pubmed/26147502
http://dx.doi.org/10.1371/journal.pone.0132560
work_keys_str_mv AT crosseyerin identificationofanimmunogenicmimicofaconservedepitopeontheplasmodiumfalciparumbloodstageantigenama1usingviruslikeparticlevlppeptidedisplay
AT frietzekathryn identificationofanimmunogenicmimicofaconservedepitopeontheplasmodiumfalciparumbloodstageantigenama1usingviruslikeparticlevlppeptidedisplay
AT narumdavidl identificationofanimmunogenicmimicofaconservedepitopeontheplasmodiumfalciparumbloodstageantigenama1usingviruslikeparticlevlppeptidedisplay
AT peabodydavids identificationofanimmunogenicmimicofaconservedepitopeontheplasmodiumfalciparumbloodstageantigenama1usingviruslikeparticlevlppeptidedisplay
AT chackerianbryce identificationofanimmunogenicmimicofaconservedepitopeontheplasmodiumfalciparumbloodstageantigenama1usingviruslikeparticlevlppeptidedisplay