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

C Gomes, Ariane; Rösti, Elisa Simona; El-Turabi, Aadil; Bachmann, Martin F. (2019). Type of RNA Packed in VLPs Impacts IgG Class Switching-Implications for an Influenza Vaccine Design. Vaccines, 7(2) MDPI 10.3390/vaccines7020047

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

UniBE Contributor:

Rösti, Elisa Simona and Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2076-393X

Publisher:

MDPI

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

18 Nov 2019 10:26

Last Modified:

18 Nov 2019 10:26

Publisher DOI:

10.3390/vaccines7020047

PubMed ID:

31167472

Uncontrolled Keywords:

IgG RNA TLR7 VLPs

BORIS DOI:

10.7892/boris.135091

URI:

https://boris.unibe.ch/id/eprint/135091

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