Immunogenicity and efficacy of two types of West Nile virus-like particles different in size and maturation as a second-generation vaccine candidate

Ohtaki, Naohiro; Takahashi, Hitomi; Kaneko, Keiko; Gomi, Yasuo; Ishikawa, Takahiro; Higashi, Yutaro; Kurata, Takeshi; Sata, Tetsutaro; Kojima, Asato

doi:10.1016/j.vaccine.2010.07.055

Cited by 38 publications

(39 citation statements)

References 42 publications

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“…These findings are consistent with the humoral response induced by VLPs in other studies (34). All these results confirmed that the dengue virus type 1 and 2 VLPs prepared in this study preserved the antigenicity of prM and E proteins and effectively induced virus specific humoral immune responses.…”

Section: Discussionsupporting

confidence: 92%

Retracted: Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue

2015

Microbiology and Immunology

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We aimed to systematically analyze the immunological properties of monovalent and bivalent dengue virus-like particles (DENV VLPs) prepared in our study and provided basis for the development of DENV VLPs as a promising non-infectious candidate vaccine for dengue infection. The DENV-1/2 VLPs were prepared in the GAP promoter-based P.pastoris expression system using α-factor secretion signal. Groups of mice were immunized by monovalent and bivalent VLPs compared with inactivated virions and PBS. Then, the humoral immune response in mice were tested by ELISA, immunofluorescence and neutralization assay. ELISA and Enzyme linked immunospot assay were performed for investigating cytokines production after virus challenge in vivo and in vitro, respectively. Besides, the protection ability of VLPs was assessed by passive protection assay in suckling mice. The recombinant DENV-1/2 VLPs were successfully expressed with α-factor secretion signal. Sera of mice immunized with monovalent and bivalent VLPs elevated the specific antibodies level comparable to inactivated virions group. The monovalent and bivalent VLPs induced specific cellular immune response as confirmed by ELISPOT. The PRNT 50 titers of monovalent and bivalent VLPs sera against DENV-1/2 were different ranging from 16 to 64. Moreover, anti-monovalent and anti-bivalent DENV VLPs sera displayed protective capacity in survival rate and morbidity. Monovalent and bivalent VLPs showed attracting vaccine effect for dengue virus. The multivalent VLPs may be promising for preventing different types of dengue virus.

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Section: Discussionsupporting

confidence: 92%

Retracted: Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue

2015

Microbiology and Immunology

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“…Exploitation of these post-translational control measures has facilitated the continuing development of novel vaccines and therapeutics for use against flavivirus infections (Goto et al, 2005;Keelapang et al, 2013;Ohtaki et al, 2010;Pang et al, 2014;Roby et al, 2011Roby et al, , 2013Roby et al, , 2014Zhang et al, 2011).…”

Section: Flavivirusesmentioning

confidence: 99%

“…These heterodimers coalesce on the lumenal face of the ER membrane forming trimeric spikes and ultimately bud off to give rise to either empty prM/E particles, or nucleocapsidcontaining immature virions (Roby et al, 2012). The observed formation and secretion of prM/E particles upon ectopic prM and E expression as part of a recombinant gene cassette (Allison et al, 1995;Goto et al, 2005;Konishi & Mason, 1993;Ohtaki et al, 2010;Zhang et al, 2011) suggest that this process is intrinsic to the prM and E proteins. This hypothesis is supported by a recent analysis of WNV and DENV membrane curvature induced by the arrangement of prM and E within the virus particle, suggesting that the overall spherical shape of the particles may be attributable to viral protein interaction with lipids without the need of assistance from host cellular factors (Zhang et al, 2013a).…”

Section: E Proteinmentioning

confidence: 99%

“…By purifying their prM/E particle vaccine using sucrose gradients, Ohtaki et al (2010) found that they could separate fully mature, M-containing particles [fast-sedimenting VLPs (F-VLPs)] from immature, prM-containing particles [slowsedimenting VLPs (S-VLPs)]. Subsequently, it was discovered that F-VLPs with fully matured M elicited a more robust immune response than S-VLPs with uncleaved prM.…”

Section: Post-translational Modification Of Structural Proteins In Vamentioning

confidence: 99%

“…pH environments and the infectivity of mature virus particles (Beasley et al, 2005; Goto et al, 2005;Guirakhoo et al, 1993;Hanna et al, 2005;Lee et al, 1997Lee et al, , 2010Li et al, 2006;Mondotte et al, 2007;Scherret et al, 2001). Exploitation of these post-translational control measures has facilitated the continuing development of novel vaccines and therapeutics for use against flavivirus infections (Goto et al, 2005; Keelapang et al, 2013;Ohtaki et al, 2010;Pang et al, 2014;Roby et al, 2011Roby et al, , 2013Roby et al, , 2014Zhang et al, 2011). …”

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Post-translational regulation and modifications of flavivirus structural proteins

Roby

Setoh

Hall

et al. 2015

Journal of General Virology

102

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Flaviviruses are a group of single-stranded, positive-sense RNA viruses that generally circulate between arthropod vectors and susceptible vertebrate hosts, producing significant human and veterinary disease burdens. Intensive research efforts have broadened our scientific understanding of the replication cycles of these viruses and have revealed several elegant and tightly co-ordinated post-translational modifications that regulate the activity of viral proteins. The three structural proteins in particular -capsid (C), pre-membrane (prM) and envelope (E) -are subjected to strict regulatory modifications as they progress from translation through virus particle assembly and egress. The timing of proteolytic cleavage events at the C-prM junction directly influences the degree of genomic RNA packaging into nascent virions. Proteolytic maturation of prM by host furin during Golgi transit facilitates rearrangement of the E proteins at the virion surface, exposing the fusion loop and thus increasing particle infectivity. Specific interactions between the prM and E proteins are also important for particle assembly, as prM acts as a chaperone, facilitating correct conformational folding of E. It is only once prM/E heterodimers form that these proteins can be secreted efficiently. The addition of branched glycans to the prM and E proteins during virion transit also plays a key role in modulating the rate of secretion, pH sensitivity and infectivity of flavivirus particles. The insights gained from research into post-translational regulation of structural proteins are beginning to be applied in the rational design of improved flavivirus vaccine candidates and make attractive targets for the development of novel therapeutics. FlavivirusesThe genus Flavivirus in the family Flaviviridae comprises small, enveloped viruses with non-segmented genomes consisting of single-stranded, positive-sense RNA. These RNA genomes are flanked by 59 and 39 untranslated regions (UTRs) and encode a single polyprotein that is cleaved coand post-translationally to generate between 10 and 11 viral proteins. The 59 UTR contains a type 1 m 7 GpppNm cap structure and the 39 UTR lacks a polyadenylated tail. Structural elements within the UTRs regulate genome replication, translation and host immune responses. Viral proteins are divided between structural proteins, which form the virion, and non-structural proteins, which are involved in genomic replication and modulating host immunity (Fig. 1a) (Lindenbach et al., 2007;Roby et al., 2012).Flaviviruses are maintained predominantly in natural transmission cycles between vertebrate reservoir species (normally mammalian or avian) and haematophagous arthropod vectors (mosquitoes or ticks). Notable exceptions are the viruses that are maintained solely in mosquito hosts (insectspecific flaviviruses) and viruses with no known invertebrate vector (Cook et al., 2012;Mackenzie et al., 2004). As of 2013, the International Committee on Taxonomy of Viruses has classified 53 different viral species as belonging to ...

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Pathogenesis of West Nile Virus in Humans

Vandergaast

Hussmann

Fredericksen

2015

Human Emerging and Re‐emerging Infections

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Immunogenicity and efficacy of two types of West Nile virus-like particles different in size and maturation as a second-generation vaccine candidate

Cited by 38 publications

References 42 publications

Retracted: Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue

Retracted: Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue

Post-translational regulation and modifications of flavivirus structural proteins

Pathogenesis of West Nile Virus in Humans

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