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Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design

Dengue virus (DENV) is a global health problem, with over half of the world’s population at risk for infection. Despite this, there is only one licensed vaccine available to prevent infection and safety concerns limit immunization to only a subset of individuals. Most dengue virus vaccine efforts at...

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Autores principales: Warner, Nikole L., Core, Susan B., Frietze, Kathryn M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784660/
https://www.ncbi.nlm.nih.gov/pubmed/36560438
http://dx.doi.org/10.3390/vaccines10122028
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author Warner, Nikole L.
Core, Susan B.
Frietze, Kathryn M.
author_facet Warner, Nikole L.
Core, Susan B.
Frietze, Kathryn M.
author_sort Warner, Nikole L.
collection PubMed
description Dengue virus (DENV) is a global health problem, with over half of the world’s population at risk for infection. Despite this, there is only one licensed vaccine available to prevent infection and safety concerns limit immunization to only a subset of individuals. Most dengue virus vaccine efforts attempt to evoke broadly neutralizing antibodies against structural proteins. However, eliciting antibodies to block the activity of viral proteins involved in pathogenesis could be a useful complementary approach. Studies suggest that non-structural protein 1, which participates in disruption of the endothelial barrier and is hypothesized to play a significant role in the progression to severe dengue, could be a promising target for vaccine efforts. Here, we used an unbiased approach to identify peptide epitopes of dengue virus non-structural protein 1 that could evoke antibodies that bind to NS1 from all 4 serotypes and also bind to DENV-infected cells. DENV-2 NS1 peptides were generated such that 35 overlapping 15 amino acid peptides represented the entire NS1 protein. These peptides were each chemically conjugated to bacteriophage virus-like particles (VLP) and used to immunize mice. Sera were then screened for IgG to cognate peptide as well as binding to recombinant hexameric NS1 from all four DENV serotypes as well as binding to DENV-2 infected cells by microscopy. From these data, we identified several peptides that were able to elicit antibodies that could bind to infected cells as well as DENV NS1. These peptides and their homologues in the corresponding NS1 of other DENV serotypes could be used as potential immunogens to elicit binding antibodies to NS1. Future studies will investigate the functional and protective capacities of antibodies elicited by these immunogens against DENV NS1.
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spelling pubmed-97846602022-12-24 Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design Warner, Nikole L. Core, Susan B. Frietze, Kathryn M. Vaccines (Basel) Article Dengue virus (DENV) is a global health problem, with over half of the world’s population at risk for infection. Despite this, there is only one licensed vaccine available to prevent infection and safety concerns limit immunization to only a subset of individuals. Most dengue virus vaccine efforts attempt to evoke broadly neutralizing antibodies against structural proteins. However, eliciting antibodies to block the activity of viral proteins involved in pathogenesis could be a useful complementary approach. Studies suggest that non-structural protein 1, which participates in disruption of the endothelial barrier and is hypothesized to play a significant role in the progression to severe dengue, could be a promising target for vaccine efforts. Here, we used an unbiased approach to identify peptide epitopes of dengue virus non-structural protein 1 that could evoke antibodies that bind to NS1 from all 4 serotypes and also bind to DENV-infected cells. DENV-2 NS1 peptides were generated such that 35 overlapping 15 amino acid peptides represented the entire NS1 protein. These peptides were each chemically conjugated to bacteriophage virus-like particles (VLP) and used to immunize mice. Sera were then screened for IgG to cognate peptide as well as binding to recombinant hexameric NS1 from all four DENV serotypes as well as binding to DENV-2 infected cells by microscopy. From these data, we identified several peptides that were able to elicit antibodies that could bind to infected cells as well as DENV NS1. These peptides and their homologues in the corresponding NS1 of other DENV serotypes could be used as potential immunogens to elicit binding antibodies to NS1. Future studies will investigate the functional and protective capacities of antibodies elicited by these immunogens against DENV NS1. MDPI 2022-11-27 /pmc/articles/PMC9784660/ /pubmed/36560438 http://dx.doi.org/10.3390/vaccines10122028 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Warner, Nikole L.
Core, Susan B.
Frietze, Kathryn M.
Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design
title Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design
title_full Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design
title_fullStr Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design
title_full_unstemmed Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design
title_short Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design
title_sort unbiased identification of dengue virus non-structural protein 1 peptides for use in vaccine design
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784660/
https://www.ncbi.nlm.nih.gov/pubmed/36560438
http://dx.doi.org/10.3390/vaccines10122028
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