Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like Particles

We have recently shown that tubular form of rotavirus (RV) recombinant VP6 protein has an in vivo adjuvant effect on the immunogenicity of norovirus (NoV) virus-like particle (VLP) vaccine candidate. In here, we investigated in vitro effect of VP6 on antigen presenting cell (APC) activation and matu...

Full description

Saved in:
Bibliographic Details
Main Authors: Maria Malm, Kirsi Tamminen, Suvi Lappalainen, Timo Vesikari, Vesna Blazevic
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/9171632
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850158215013072896
author Maria Malm
Kirsi Tamminen
Suvi Lappalainen
Timo Vesikari
Vesna Blazevic
author_facet Maria Malm
Kirsi Tamminen
Suvi Lappalainen
Timo Vesikari
Vesna Blazevic
author_sort Maria Malm
collection DOAJ
description We have recently shown that tubular form of rotavirus (RV) recombinant VP6 protein has an in vivo adjuvant effect on the immunogenicity of norovirus (NoV) virus-like particle (VLP) vaccine candidate. In here, we investigated in vitro effect of VP6 on antigen presenting cell (APC) activation and maturation and whether VP6 facilitates NoV VLP uptake by these APCs. Mouse macrophage cell line RAW 264.7 and dendritic cell line JAWSII were used as model APCs. Internalization of VP6, cell surface expression of CD40, CD80, CD86, and major histocompatibility class II molecules, and cytokine and chemokine production were analyzed. VP6 nanotubes were efficiently internalized by APCs. VP6 upregulated the expression of cell surface activation and maturation molecules and induced secretion of several proinflammatory cytokines and chemokines. The mechanism of VP6 action was shown to be partially dependent on lipid raft-mediated endocytic pathway as shown by methyl-β-cyclodextrin inhibition on tumor necrosis factor α secretion. These findings add to the understanding of mechanism by which VP6 exerts its immunostimulatory and immunomodulatory actions and further support its use as a part of nonlive RV-NoV combination vaccine.
format Article
id doaj-art-6b2f9bd5ddff4bac87b983ea1908b9cd
institution OA Journals
issn 2314-8861
2314-7156
language English
publishDate 2016-01-01
publisher Wiley
record_format Article
series Journal of Immunology Research
spelling doaj-art-6b2f9bd5ddff4bac87b983ea1908b9cd2025-08-20T02:23:57ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/91716329171632Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like ParticlesMaria Malm0Kirsi Tamminen1Suvi Lappalainen2Timo Vesikari3Vesna Blazevic4Vaccine Research Center, University of Tampere, Biokatu 10, 33520 Tampere, FinlandVaccine Research Center, University of Tampere, Biokatu 10, 33520 Tampere, FinlandVaccine Research Center, University of Tampere, Biokatu 10, 33520 Tampere, FinlandVaccine Research Center, University of Tampere, Biokatu 10, 33520 Tampere, FinlandVaccine Research Center, University of Tampere, Biokatu 10, 33520 Tampere, FinlandWe have recently shown that tubular form of rotavirus (RV) recombinant VP6 protein has an in vivo adjuvant effect on the immunogenicity of norovirus (NoV) virus-like particle (VLP) vaccine candidate. In here, we investigated in vitro effect of VP6 on antigen presenting cell (APC) activation and maturation and whether VP6 facilitates NoV VLP uptake by these APCs. Mouse macrophage cell line RAW 264.7 and dendritic cell line JAWSII were used as model APCs. Internalization of VP6, cell surface expression of CD40, CD80, CD86, and major histocompatibility class II molecules, and cytokine and chemokine production were analyzed. VP6 nanotubes were efficiently internalized by APCs. VP6 upregulated the expression of cell surface activation and maturation molecules and induced secretion of several proinflammatory cytokines and chemokines. The mechanism of VP6 action was shown to be partially dependent on lipid raft-mediated endocytic pathway as shown by methyl-β-cyclodextrin inhibition on tumor necrosis factor α secretion. These findings add to the understanding of mechanism by which VP6 exerts its immunostimulatory and immunomodulatory actions and further support its use as a part of nonlive RV-NoV combination vaccine.http://dx.doi.org/10.1155/2016/9171632
spellingShingle Maria Malm
Kirsi Tamminen
Suvi Lappalainen
Timo Vesikari
Vesna Blazevic
Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like Particles
Journal of Immunology Research
title Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like Particles
title_full Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like Particles
title_fullStr Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like Particles
title_full_unstemmed Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like Particles
title_short Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like Particles
title_sort rotavirus recombinant vp6 nanotubes act as an immunomodulator and delivery vehicle for norovirus virus like particles
url http://dx.doi.org/10.1155/2016/9171632
work_keys_str_mv AT mariamalm rotavirusrecombinantvp6nanotubesactasanimmunomodulatoranddeliveryvehiclefornorovirusviruslikeparticles
AT kirsitamminen rotavirusrecombinantvp6nanotubesactasanimmunomodulatoranddeliveryvehiclefornorovirusviruslikeparticles
AT suvilappalainen rotavirusrecombinantvp6nanotubesactasanimmunomodulatoranddeliveryvehiclefornorovirusviruslikeparticles
AT timovesikari rotavirusrecombinantvp6nanotubesactasanimmunomodulatoranddeliveryvehiclefornorovirusviruslikeparticles
AT vesnablazevic rotavirusrecombinantvp6nanotubesactasanimmunomodulatoranddeliveryvehiclefornorovirusviruslikeparticles