Rotavirus capsid VP6 tubular and spherical nanostructures act as local adjuvants when co-delivered with norovirus VLPs

Malm, Maria; Heinimäki, Suvi; Vesikari, Timo; Blazevic, Vesna

doi:10.1111/cei.12977

Cited by 31 publications

(36 citation statements)

References 59 publications

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“…GII.17 VLP binding was analyzed using three different sources of HBGAs, human saliva, pig gastric mucin (PGM) type III (Sigma Chemicals, St Louis, MO, USA) (23) and synthetic HBGAs. Binding assays were performed using procedures described in detail elsewhere (30,48). Briefly, 96-well half-area polystyrene plates (Costar, Corning, NY) were coated with either 2.5 µg/ml PGM or 1:3000 diluted type A, B, and O saliva from adult volunteers with previously determined ABO phenotype (48).…”

Section: Hbga Carbohydrate Binding Assaymentioning

confidence: 99%

Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup II-Specific Mouse Sera

et al. 2018

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Majority of norovirus (NoV) outbreaks and sporadic infections in the past 20 years have been caused by GII.4 variants. In 2014, norovirus GII.17 genotype replaced GII.4 strains in several Asian countries and major outbreaks were reported in other continents. As GII.17 is a recently evolved NoV strain, there is a gap especially in immunogenicity data. In the present study we investigated GII.17 virus-like particle (VLP) binding to various cellular ligands, histo-blood group antigens (HBGAs), using human saliva, pig gastric mucin, and synthetic oligosaccharides as HBGA sources. The level of GII.17 immunological cross-reactivity was determined in mice immunized with different monovalent and multivalent NoV VLP compositions. Furthermore, healthy adult volunteers with natural NoV exposure history were analyzed for GII.17-specific seroresponses. The results showed that GII.17 Kawasaki VLPs bind to a wide range of HBGAs, even though fewer than GII.4 VLPs. Immunization of mice with a multivalent VLP formulation containing different genogroup II NoV VLPs was required to obtain the highest magnitude of cross-reactive binding antibodies to GII.17. However, co-immunization with different VLP genotypes did not improve potentially neutralizing antibodies to GII.17, which remained very moderate. Low pre-existing cross-reactive antibodies to GII.17 observed in human adults indicates the presence of a large pool of susceptible individuals in this population. These data suggest that GII.17 and alike newly emerging, distinct NoV genotypes should be considered as an antigenic component for vaccine formulations, which currently widely rely on GII.4-specific immunity.

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Section: Hbga Carbohydrate Binding Assaymentioning

confidence: 99%

Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup II-Specific Mouse Sera

et al. 2018

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“…However, due to the local and systemic adverse events associated with adjuvanted vaccines [22], our hypothesis is that in the pediatric NoV vaccine candidate we developed, extremely immunogenic VP6 protein may serve to substitute the external adjuvant. To this end, we have shown that RV VP6 in our combination vaccine has an adjuvant effect on NoV immune responses in vitro and in vivo [14,[23][24][25]. The adjuvant mechanism has been studied in immortalized cell lines used as antigenpresenting cells (APCs), namely, RAW macrophages and JAWSII dendritic cells (DCs), and the results suggested that VP6 acts as an immunomodulator and immunostimulator and facilitates NoV VLPs internalization by the APCs [23].…”

Section: Introductionmentioning

confidence: 91%

Rotavirus VP6 Adjuvant Effect on Norovirus GII.4 Virus-Like Particle Uptake and Presentation by Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo

Tamminen

Heinimäki

Vesikari

et al. 2020

Journal of Immunology Research

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We have previously shown that rotavirus (RV) inner capsid protein VP6 has an adjuvant effect on norovirus (NoV) virus-like particle- (VLP-) induced immune responses and studied the adjuvant mechanism in immortalized cell lines used as antigen-presenting cells (APCs). Here, we investigated the uptake and presentation of RV VP6 and NoV GII.4 VLPs by primary bone marrow-derived dendritic cells (BMDCs). The adjuvant effect of VP6 on GII.4 VLP presentation and NoV-specific immune response induction by BMDC in vivo was also studied. Intracellular staining demonstrated that BMDCs internalized both antigens, but VP6 more efficiently than NoV VLPs. Both antigens were processed and presented to antigen-primed T cells, which responded by robust interferon γ secretion. When GII.4 VLPs and VP6 were mixed in the same pulsing reaction, a subpopulation of the cells had uptaken both antigens. Furthermore, VP6 copulsing increased GII.4 VLP uptake by 37% and activated BMDCs to secrete 2-5-fold increased levels of interleukin 6 and tumor necrosis factor α compared to VLP pulsing alone. When in vitro-pulsed BMDCs were transferred to syngeneic BALB/c mice, VP6 improved NoV-specific antibody responses. The results of this study support the earlier findings of VP6 adjuvant effect in vitro and in vivo.

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“…Immunization of mice with VP6‐nanotubes could also induce the highest titres of serum IgG and mucosal IgG and IgA as well as significant IFN‐γ producing T cells, which confer a higher degree of protection when compared with the immunization with DLPs or VP6 trimers . Co‐administration of VP6 nanotubes with norovirus VLPs not only induced protective immunity against RV infection but also showed an adjuvant effect of immune response for norovirus VLPs . To support this, Rodriguez et al has investigated the adjuvant effect of VP6 nanotubes and showed that nanotubes are taken up efficiently by macrophages and dendritic cells in vitro, inducing several proinflammatory cytokines and chemokines .…”

Section: Vp6 Immunogensmentioning

confidence: 99%

“…84 Co-administration of VP6 nanotubes with norovirus VLPs not only induced protective immunity against RV infection but also showed an adjuvant effect of immune response for norovirus VLPs. [86][87][88] To support this, Rodriguez et al has investigated the adjuvant effect of VP6 nanotubes and showed that nanotubes are taken up efficiently by macrophages and dendritic cells in vitro, inducing several proinflammatory cytokines and chemokines. 87,89 VP6 nanotubes were also indicated to support the internalization of co-delivered norovirus VLPs to the antigen presenting cells.…”

Section: Vp6 Dnamentioning

confidence: 99%

Rotavirus VP6 as a potential vaccine candidate

Afchangi

Jalilvand

Mohajel

et al. 2019

Reviews in Medical Virology

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Summary By the age of 5 years, virtually all children have been infected by group A rotavirus (RVA), which is responsible for around half million mortality annually prior to vaccination. Relatively high rate of the morbidity and mortality highlights the necessity of applying preventive procedures particularly in developing countries. Two live attenuated RVA vaccines (Rotarix and RotaTeq) are licensed and now being used in many countries worldwide. Although these vaccines are shown to reduce the mortality up to 50%, several key questions yet remained to answer. Indeed, the licensed RV vaccines were found to be less effective in countries of sub‐Saharan Africa and Southeast Asia. Therefore, developing next generation RVA vaccines is warranted. VP6 is highly abundant and conserved protein that forms the middle layer of RV particles and was shown to be both antigenic and immunogenic. Although it does not induce neutralizing antibodies, different VP6 preparations were found to induce homologous and cross‐reactive immune responses with partial protection from RVA replication. Although the molecular mechanisms are not fully elucidated, VP6‐based RVA vaccine candidates are worthy of further consideration. This review aims to focus on different aspects of VP6 protein and its potentiality for an alternative RV vaccine against RV disease.

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Rotavirus capsid VP6 tubular and spherical nanostructures act as local adjuvants when co-delivered with norovirus VLPs

Cited by 31 publications

References 59 publications

Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup II-Specific Mouse Sera

Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup II-Specific Mouse Sera

Rotavirus VP6 Adjuvant Effect on Norovirus GII.4 Virus-Like Particle Uptake and Presentation by Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo

Rotavirus VP6 as a potential vaccine candidate

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