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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/7/2/47 |
| _version_ | 1811183969902788608 |
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| author | Ariane C. Gomes E. S. Roesti Aadil El-Turabi Martin F. Bachmann |
| author_facet | Ariane C. Gomes E. S. Roesti Aadil El-Turabi Martin F. Bachmann |
| author_sort | Ariane C. Gomes |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T13:06:41Z |
| format | Article |
| id | doaj.art-028c9086cdf444bc86a0aa813dbed139 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T13:06:41Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-028c9086cdf444bc86a0aa813dbed1392022-12-22T04:22:43ZengMDPI AGVaccines2076-393X2019-06-01724710.3390/vaccines7020047vaccines7020047Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine DesignAriane C. Gomes0E. S. Roesti1Aadil El-Turabi2Martin F. Bachmann3The Jenner Institute, Oxford University, Oxford OX3 7BN, UKDepartment for BioMedical Research (DBMR), Inselspital, University of Bern, 3010 Bern, SwitzerlandThe Jenner Institute, Oxford University, Oxford OX3 7BN, UKThe Jenner Institute, Oxford University, Oxford OX3 7BN, UKNucleic 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.https://www.mdpi.com/2076-393X/7/2/47VLPsRNATLR7IgG |
| spellingShingle | Ariane C. Gomes E. S. Roesti Aadil El-Turabi Martin F. Bachmann Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design Vaccines VLPs RNA TLR7 IgG |
| 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 | VLPs RNA TLR7 IgG |
| url | https://www.mdpi.com/2076-393X/7/2/47 |
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