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Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines

The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. “Wild-type” viral nanoparticles can be further genetically or biochemically functionalized...

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Autores principales: Barnowski, Cornelia, Kadzioch, Nicole, Damm, Dominik, Yan, Huimin, Temchura, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572692/
https://www.ncbi.nlm.nih.gov/pubmed/31052410
http://dx.doi.org/10.3390/pharmaceutics11050204
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author Barnowski, Cornelia
Kadzioch, Nicole
Damm, Dominik
Yan, Huimin
Temchura, Vladimir
author_facet Barnowski, Cornelia
Kadzioch, Nicole
Damm, Dominik
Yan, Huimin
Temchura, Vladimir
author_sort Barnowski, Cornelia
collection PubMed
description The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. “Wild-type” viral nanoparticles can be further genetically or biochemically functionalized with biomolecules (antigens and adjuvants). Flagellin is a potent inducer of innate immunity and it has demonstrated adjuvant effectiveness due to its affinity for toll-like receptor 5 (TLR5). In contrast to most TLR ligands, flagellin is a protein and can induce an immune response against itself. To avoid side-effects, we incorporated a less inflammatory and less immunogenic form of flagellin as an adjuvant into HIV-based nanoparticle B-cell-targeting vaccines that display either the HIV-1 envelope protein (Env) or a model antigen, hen egg lysozyme (HEL). While flagellin significantly enhanced HEL-specific IgG responses, anti-Env antibody responses were suppressed. We demonstrated that flagellin did not activate B-cells directly in vitro, but might compete for CD4+ T-cell help in vivo. Therefore, we hypothesize that in the context of VLP-based B-cell nano-vaccines, flagellin serves as an antigen itself and may outcompete a less immunogenic antigen with its antibody response. In contrast, in combination with a strong immunogen, the adjuvant activity of flagellin may dominate over its immunogenicity.
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spelling pubmed-65726922019-06-18 Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines Barnowski, Cornelia Kadzioch, Nicole Damm, Dominik Yan, Huimin Temchura, Vladimir Pharmaceutics Article The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. “Wild-type” viral nanoparticles can be further genetically or biochemically functionalized with biomolecules (antigens and adjuvants). Flagellin is a potent inducer of innate immunity and it has demonstrated adjuvant effectiveness due to its affinity for toll-like receptor 5 (TLR5). In contrast to most TLR ligands, flagellin is a protein and can induce an immune response against itself. To avoid side-effects, we incorporated a less inflammatory and less immunogenic form of flagellin as an adjuvant into HIV-based nanoparticle B-cell-targeting vaccines that display either the HIV-1 envelope protein (Env) or a model antigen, hen egg lysozyme (HEL). While flagellin significantly enhanced HEL-specific IgG responses, anti-Env antibody responses were suppressed. We demonstrated that flagellin did not activate B-cells directly in vitro, but might compete for CD4+ T-cell help in vivo. Therefore, we hypothesize that in the context of VLP-based B-cell nano-vaccines, flagellin serves as an antigen itself and may outcompete a less immunogenic antigen with its antibody response. In contrast, in combination with a strong immunogen, the adjuvant activity of flagellin may dominate over its immunogenicity. MDPI 2019-05-01 /pmc/articles/PMC6572692/ /pubmed/31052410 http://dx.doi.org/10.3390/pharmaceutics11050204 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Barnowski, Cornelia
Kadzioch, Nicole
Damm, Dominik
Yan, Huimin
Temchura, Vladimir
Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines
title Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines
title_full Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines
title_fullStr Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines
title_full_unstemmed Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines
title_short Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines
title_sort advantages and limitations of integrated flagellin adjuvants for hiv-based nanoparticle b-cell vaccines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572692/
https://www.ncbi.nlm.nih.gov/pubmed/31052410
http://dx.doi.org/10.3390/pharmaceutics11050204
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