Gold nanorod vaccine for respiratory syncytial virus

Stone, John W.; Thornburg, Natalie J.; Blum, David; Kuhn, Samuel; Wright, David W.; Crowe, James E.

doi:10.1088/0957-4484/24/29/295102

Cited by 69 publications

(41 citation statements)

References 28 publications

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“…The vast majority of the reports of tests of vaccine potential concern heterologous VLPs or nanoparticles carrying the hRSV F and/or G protein, in part because these systems are established or efficient and because hRSV particle assembly is poorly understood. The heterologous systems include Newcastle disease virus-, Sendai virus-, or baculovirus-based VLPs; nanoparticles; and gold-based nanorods and have shown encouraging results in the BALB/c mouse model (6)(7)(8)(9)(10)(11)(12) and humans (13,14). In comparison, authentic hRSV VLPs structurally resemble wild-type (wt) virions and also incorporate some of the internal hRSV proteins (5), features that may be advantageous for vaccine purposes.…”

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confidence: 99%

The Respiratory Syncytial Virus Phosphoprotein, Matrix Protein, and Fusion Protein Carboxy-Terminal Domain Drive Efficient Filamentous Virus-Like Particle Formation

Meshram

Baviskar

Ognibene

et al. 2016

J Virol

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Virus-like particles (VLPs) are attractive as a vaccine concept. For human respiratory syncytial virus (hRSV), VLP assembly is poorly understood and appears inefficient. Hence, hRSV antigens are often incorporated into foreign VLP systems to generate anti-RSV vaccine candidates. To better understand the assembly, and ultimately to enable efficient production, of authentic hRSV VLPs, we examined the associated requirements and mechanisms. In a previous analysis in HEp-2 cells, the nucleoprotein (N), phosphoprotein (P), matrix protein (M), and fusion protein (F) were required for formation of filamentous VLPs, which, similar to those of wild-type virus, were associated with the cell surface. Using fluorescence and electron microscopy combined with immunogold labeling, we examined the surfaces of transfected HEp-2 cells and further dissected the process of filamentous VLP formation. Our results show that N is not required. Coexpression of P plus M plus F, but not P plus M, M plus F, or P plus F, induced both viral protein coalescence and formation of filamentous VLPs that resembled wild-type virions. Despite suboptimal coalescence in the absence of P, the M and F proteins, when coexpressed, formed cell surface-associated filaments with abnormal morphology, appearing longer and thinner than wild-type virions. For F, only the carboxy terminus (Fstem) was required, and addition of foreign protein sequences to Fstem allowed incorporation into VLPs. Together, the data show that P, M, and the F carboxy terminus are sufficient for robust viral protein coalescence and filamentous VLP formation and suggest that M-F interaction drives viral filament formation, with P acting as a type of cofactor facilitating the process and exerting control over particle morphology. IMPORTANCEhRSV is responsible for >100,000 deaths in children worldwide, and a vaccine is not available. Among the potential anti-hRSV approaches are virus-like particle (VLP) vaccines, which, based on resemblance to virus or viral components, can induce protective immunity. For hRSV, few reports are available concerning authentic VLP production or testing, in large part because VLP production is inefficient and the mechanisms underlying particle assembly are poorly understood. Here, we took advantage of the cell-associated nature of RSV particles and used high-resolution microscopy analyses to examine the viral proteins required for formation of wild-type-virus-resembling VLPs, the contributions of these proteins to morphology, and the domains involved in incorporation of the antigenically important viral F protein. The results provide new insights that will facilitate future production of hRSV VLPs with defined shapes and compositions and may translate into improved manufacture of live-attenuated hRSV vaccines. H uman respiratory syncytial virus (hRSV) is an important viral agent of respiratory tract disease in infants, children, immunosuppressed individuals, and the elderly (1-3). In pursuit of a vaccine to prevent hRSV disease, a virus-like particle (...

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confidence: 99%

The Respiratory Syncytial Virus Phosphoprotein, Matrix Protein, and Fusion Protein Carboxy-Terminal Domain Drive Efficient Filamentous Virus-Like Particle Formation

Meshram

Baviskar

Ognibene

et al. 2016

J Virol

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“…15 Additionally, GNRs have been explored as a RSV vaccine delivery. 21 Some studies with metallic nanoparticles have been performed in animals with respect to respiratory viruses. However, there is need to understand the molecular events associated with nanoparticle-based viral inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Gold nanomaterials are gaining popularity due to their surface structure, low toxicity and their potential for a wide range of biomedical applications. Gold nanorods (GNRs) are currently being investigated for treatment of cancer, 17–19 HIV, 20 Respiratory Syncytial Virus (RSV), 21 and for various biomedical applications. 22 …”

Section: Introductionmentioning

confidence: 99%

Gold nanorods inhibit respiratory syncytial virus by stimulating the innate immune response

Bawage

Tiwari

Singh

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Respiratory syncytial virus (RSV) causes severe pneumonia and bronchiolitis in infants, children and older adults. The use of metallic nanoparticles as potential therapeutics is being explored against respiratory viruses like Influenza, Parainfluenza and Adenovirus. In this study, we showed that gold nanorods (GNRs) inhibit RSV in HEp-2 cells and BALB/c mice by 82% and 56%, respectively. The RSV inhibition correlated with marked upregulated antiviral genes due to GNR mediated TLR, NOD-like receptor and RIG-I-like receptor signaling pathways. Transmission electron microscopy of lungs showed GNRs in the endocytotic vesicles and histological analyses indicated infiltration by neutrophils, eosinophils and monocytes correlating with clearance of RSV. In addition, production of cytokines and chemokines in the lungs indicate recruitment of immune cells to counter RSV replication. To our knowledge, this is the first in vitro and in vivo report that provides possible antiviral mechanisms of GNRs against RSV.

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“…Furthermore, the shape/structure of a nanoparticle can also be important for interaction with the immune system, especially in terms of proper conformational display of an antigen in vaccine particles [90–94]. …”

Section: Nanoparticles and The Immune Systemmentioning

confidence: 99%

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

Neef

Miller

2017

Curr Diab Rep

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Purpose of Review The current standard therapy for type 1 diabetes (T1D) is insulin replacement. Autoimmune diseases are typically treated with broad immunosuppression, but this has multiple disadvantages. Induction of antigen-specific tolerance is preferable. The application of nanomedicine to the problem of T1D can take different forms, but one promising way is the development of tolerogenic nanoparticles, the aim of which is to mitigate the islet-destroying autoimmunity. We review the topic and highlight recent strategies to produce tolerogenic nanoparticles for the purpose of treating T1D. Recent Findings Several groups are making progress in applying tolerogenic nanoparticles to rodent models of T1D, while others are using nanotechnology to aid other potential T1D treatments such as islet transplant and islet encapsulation. Summary The strategies behind how nanoparticles achieve tolerance are varied. It is likely the future will see even greater diversity in tolerance induction strategies as well as a greater focus on how to translate this technology from preclinical use in mice to treatment of T1D in humans.

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Gold nanorod vaccine for respiratory syncytial virus

Cited by 69 publications

References 28 publications

The Respiratory Syncytial Virus Phosphoprotein, Matrix Protein, and Fusion Protein Carboxy-Terminal Domain Drive Efficient Filamentous Virus-Like Particle Formation

The Respiratory Syncytial Virus Phosphoprotein, Matrix Protein, and Fusion Protein Carboxy-Terminal Domain Drive Efficient Filamentous Virus-Like Particle Formation

Gold nanorods inhibit respiratory syncytial virus by stimulating the innate immune response

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

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