Comparative immunogenicity in mice of rotavirus VP6 tubular structures and virus-like particles

Lappalainen, Sanna; Tamminen, Kirsi; Vesikari, Timo; Blazevic, Vesna

doi:10.4161/hv.25249

Cited by 32 publications

(51 citation statements)

References 53 publications

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“…We further determined if there is a difference in VP6 adjuvant effect induced with VP6T or VP6S, as both tubular as well as spherical structures were shown previously to be highly immunogenic in mice . When 10 μg VP6S were co‐delivered with the VLPs instead of the VP6T, comparable IgG titres were observed ( P = 0·211) (Fig.…”

Section: Resultsmentioning

confidence: 84%

“…VP6 forms trimers organized into hexagons and packed into higher‐order structural assemblies, e.g. VP6 nanotubes (VP6T) and nanospheres (VP6S), when expressed in vitro under different conditions . The rVP6 is highly immunogenic , and it has also been used as a carrier or delivery platform for heterologous protein antigens and genetically fused epitope‐based vaccines, with improved response to the foreign antigen .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Malm

Heinimäki

Vesikari

et al. 2017

Clinical and Experimental Immunology

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SummaryA subunit protein vaccine candidate based on norovirus (NoV) virus‐like particles (VLPs) and rotavirus (RV) VP6 protein against acute childhood gastroenteritis has been proposed recently. RV VP6 forms different oligomeric nanostructures, including tubes and spheres when expressed in vitro, which are highly immunogenic in different animal models. We have shown recently that recombinant VP6 nanotubes have an adjuvant effect on immunogenicity of NoV VLPs in mice. In this study, we investigated if the adjuvant effect is dependent upon a VP6 dose or different VP6 structural assemblies. In addition, local and systemic adjuvant effects as well as requirements for antigen co‐delivery and co‐localization were studied. The magnitude and functionality of NoV GII.4‐specific antibodies and T cell responses were tested in mice immunized with GII.4 VLPs alone or different combinations of VLPs and VP6. A VP6 dose‐dependent adjuvant effect on GII.4‐specific antibody responses was observed. The adjuvant effect was found to be strictly dependent upon co‐administration of NoV GII.4 VLPs and VP6 at the same anatomic site and at the same time. However, the adjuvant effect was not dependent on the types of oligomers used, as both nanotubes and nanospheres exerted adjuvant effect on GII.4‐specific antibody generation and, for the first time, T cell immunity. These findings elucidate the mechanisms of VP6 adjuvant effect in vivo and support its use as an adjuvant in a combination NoV and RV vaccine.

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Section: Resultsmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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

Malm

Heinimäki

Vesikari

et al. 2017

Clinical and Experimental Immunology

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“…In particular, elongated tubular structures of VP6 not only induce higher level of immunogenicity compared with trimers or spherical structures of VP6 [149,151], but also may have the potential to act as an adjuvant [152,153] suggesting the reliance of the Ab response induction on the protein quaternary structure [154]. To support this, a comparison of the immunogenicity of recombinant tubular VP6 and DLP2/6 [24] has shown that both tubular VP6 and DLP2/6 are able to induce similar effective humoral and cellular responses against RV in mice [24].…”

Section: The Different Structures Of Vp6 (Trimers Tubules and Sphermentioning

confidence: 97%

“…New approaches consisting of non-replicating RV strains or RV proteins are currently undertaken [6,12,13], which focused on inactivated RV strains [14][15][16][17][18][19], virus-like particles (VLPs), and VP6 subunit [13,20]. VP6-based vaccine candidates provided promising results by inducing heterologous cross-protective RV immunity in mice [21][22][23] although induced antibodies (Abs) against VP6 are not neutralizing (NT) [24]. VP6, the most immunogenic, antigenic, and abundant RV protein [25,26], is highly conserved that contains viral group-and subgroup (SG)-specific determinants [27].…”

Section: Introductionmentioning

confidence: 99%

Rotavirus VP6 preparations as a non-replicating vaccine candidates

Jalilvand

Marashi

Shoja

2015

Vaccine

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“…Recombinant VP6 (rVP6) and double-layered (dl) 2/6-virus-like particles (VLPs) were considered as the simplest RV subunit vaccine (1,20). Both the rVP6 and dl2/6-VLPs induced a balanced Th1-type and Th2-type response and high levels of serum IgG antibodies with cross-reactivities against different RV strains (Wa, SC2, BrB, 69M, L26, WC3, and RRV).…”

Section: Introductionmentioning

confidence: 99%

A New Rotavirus VP6-Based Foreign Epitope Presenting Vector and Immunoreactivity of VP4 Epitope Chimeric Proteins

Teng

Zhao²,

Pan³

et al. 2014

Viral Immunology

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The VP6, the group antigenic rotavirus (RV), is highly conserved and the most abundant, constituting about 39% of the viral structure proteins by weight. The high degree of identity ( > 87%-99%) in the primary amino acid sequences suggests VP6-based vaccines could potentially provide heterotypic protection. Although some efforts have been made toward producing recombinant rotavirus VP6 vaccines, the native VP6 is still unsatisfactory as an optimal vaccine. The major neutralizing antigenic epitopes that exist on VP4 or VP7 are not on the native VP6, and as a vector the native VP6 lacks insertion sites that can be used for insertion of foreign epitopes. In this study, a new foreign epitope presenting system using VP6 as a vector (VP6F) was constructed on the outer surface of the vector six sites that could be used for insertion of the foreign epitopes created. Using this system, three VP6-based VP4 epitope chimeric proteins were constructed. Results showed that these chimeric proteins reacted with anti-VP6 and -VP4 antibodies, and elicited antibodies against VP6 and VP4 in guinea pigs. Antibodies against VP6F or antibodies against the chimeric proteins neutralized RV Wa and SA11 infection in vitro. It is optimistic that the limitation for using the native VP6 as a vaccine candidate or vector will be solved with our proposed approach. It is expected that this VP6-based epitope presenting system and the VP6-based VP4 epitope chimeric proteins will be valuable for and contribute to the development of novel RV vaccines and vaccine vectors.

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Comparative immunogenicity in mice of rotavirus VP6 tubular structures and virus-like particles

Cited by 32 publications

References 53 publications

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

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

Rotavirus VP6 preparations as a non-replicating vaccine candidates

A New Rotavirus VP6-Based Foreign Epitope Presenting Vector and Immunoreactivity of VP4 Epitope Chimeric Proteins

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