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Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design

Nucleic acid packed within virus-like particles (VLPs) is shown to shape the immune response and to induce stronger B cell responses in different immunisation models. Here, using a VLP displaying the highly conserved extracellular domain of the M2 protein (M2e) from the influenza viruses as an antig...

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Autores principales: C. Gomes, Ariane, Roesti, E. S., El-Turabi, Aadil, Bachmann, Martin F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630894/
https://www.ncbi.nlm.nih.gov/pubmed/31167472
http://dx.doi.org/10.3390/vaccines7020047
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author C. Gomes, Ariane
Roesti, E. S.
El-Turabi, Aadil
Bachmann, Martin F.
author_facet C. Gomes, Ariane
Roesti, E. S.
El-Turabi, Aadil
Bachmann, Martin F.
author_sort C. Gomes, Ariane
collection PubMed
description Nucleic acid packed within virus-like particles (VLPs) is shown to shape the immune response and to induce stronger B cell responses in different immunisation models. Here, using a VLP displaying the highly conserved extracellular domain of the M2 protein (M2e) from the influenza viruses as an antigen, we demonstrate that the type of RNA packaged into VLPs can alter the quality of the induced humoral response. By comparing prokaryotic RNA (pRNA), eukaryotic RNA (eRNA) and transfer RNA (tRNA), we find that pRNA induces the most protective IgG subclasses using a murine influenza model. We provide evidence that this process is predominantly dependent on endosomal Toll-like receptor (TLR7), and rule out a role for cytoplasmic mitochondrial antiviral signalling protein (MAVS) and its upstream retinoic acid-inducible gene-I-like receptors (RIG-I). Our findings provide considerations for the rational design of VLP-based vaccines and the immunomodulation exerted by TLR7 ligands packaged within the particles. Based on this work, we conclude that VLPs packing prokaryotic RNA must be preferred whenever a response dominated by IgG2 is desired, while eukaryotic RNA should be employed in order to induce a response dominated by IgG1.
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spelling pubmed-66308942019-08-19 Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design C. Gomes, Ariane Roesti, E. S. El-Turabi, Aadil Bachmann, Martin F. Vaccines (Basel) Article Nucleic acid packed within virus-like particles (VLPs) is shown to shape the immune response and to induce stronger B cell responses in different immunisation models. Here, using a VLP displaying the highly conserved extracellular domain of the M2 protein (M2e) from the influenza viruses as an antigen, we demonstrate that the type of RNA packaged into VLPs can alter the quality of the induced humoral response. By comparing prokaryotic RNA (pRNA), eukaryotic RNA (eRNA) and transfer RNA (tRNA), we find that pRNA induces the most protective IgG subclasses using a murine influenza model. We provide evidence that this process is predominantly dependent on endosomal Toll-like receptor (TLR7), and rule out a role for cytoplasmic mitochondrial antiviral signalling protein (MAVS) and its upstream retinoic acid-inducible gene-I-like receptors (RIG-I). Our findings provide considerations for the rational design of VLP-based vaccines and the immunomodulation exerted by TLR7 ligands packaged within the particles. Based on this work, we conclude that VLPs packing prokaryotic RNA must be preferred whenever a response dominated by IgG2 is desired, while eukaryotic RNA should be employed in order to induce a response dominated by IgG1. MDPI 2019-06-04 /pmc/articles/PMC6630894/ /pubmed/31167472 http://dx.doi.org/10.3390/vaccines7020047 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
C. Gomes, Ariane
Roesti, E. S.
El-Turabi, Aadil
Bachmann, Martin F.
Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design
title Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design
title_full Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design
title_fullStr Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design
title_full_unstemmed Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design
title_short Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design
title_sort type of rna packed in vlps impacts igg class switching—implications for an influenza vaccine design
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630894/
https://www.ncbi.nlm.nih.gov/pubmed/31167472
http://dx.doi.org/10.3390/vaccines7020047
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