Silica vesicles as nanocarriers and adjuvants for generating both antibody and T-cell mediated immune resposes to Bovine Viral Diarrhoea Virus E2 protein

Mody, Karishma T.; Mahony, Timothy J.; Zhang, Jun; Cavallaro, Antonino S.; Zhang, Bing; Popat, Amirali; Mahony, Timothy J.; Yu, Chengzhong; Mitter, Neena

doi:10.1016/j.biomaterials.2014.08.044

Cited by 39 publications

(39 citation statements)

References 66 publications

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“…In this study, both VirB9-1 and VirB10 were fully absorbed within SV-100 silica vesicles at ratio of 200 µg antigen per mg of SV-100. The absorbed protein release experiment of ViB9-1/VirB10 adsorbed SV-100 at 37 °C in PBS buffer showed that VirB9-1/VirB10 once adsorbed to SV-100 did not dissociate immediately, a similar result to previously reported study [18]. The efficient adsorption of VirB9-1/VirB10 to SV-100 and slow dissolution of protein adsorbed SV-100 is likely to enhance the uptake of antigen by antigen presenting cells.…”

Section: Discussionsupporting

confidence: 86%

“…Proteins with hydrodynamic diameter that is smaller than the pore entrance diameter can easily enter the mesopores, while the ones with larger diameter adsorb on the outer surface of the nanoparticles [29]. The specially designed novel SV-100 (50 nm diameter) silica vesicles with high protein adsorption capacities [24] have been shown to be a potential self-adjuvant with high levels of both humoral and cell-mediated immune responses in mice with no detrimental toxicity effects [18]. The SV-100 which has an entrance size of ~6 nm has been shown to be efficiently up-taken by dendritic cells, and its spherical shape similar to a virus also enhances higher antibody response compared to other shapes of similar size [19].…”

Section: Discussionmentioning

confidence: 99%

“…Due to the low immunogenicity of many purified recombinant proteins, they require the inclusion of adjuvants or carriers in subunit vaccine formulations to enhance antigen specific immune responses [18,19]. Recently, mesoporous silica nanoparticles (MSNs) have been successfully used as self-adjuvanting antigen carriers that stimulate strong, durable and specific immune responses to the major immunological determinant of bovine viral diarrhoea virus 1 [18,20,21,22].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, mesoporous silica nanoparticles (MSNs) have been successfully used as self-adjuvanting antigen carriers that stimulate strong, durable and specific immune responses to the major immunological determinant of bovine viral diarrhoea virus 1 [18,20,21,22]. Silica nanoparticles known as silica vesicles (SV) have been shown to be non-toxic, have excellent biocompatibility, and induce long-term humoral and cell mediated immune responses in mice [18,19,23]. The SV-100 nanoparticles have a diameter of 50 nm with a thin outer shell of 6 nm thickness, and a pore entrance size which can be modified within the range of 5.7 nm to 16 nm.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nanoparticle-Based Delivery of Anaplasma marginale Membrane Proteins; VirB9-1 and VirB10 Produced in the Pichia pastoris Expression System

Zhang¹,

Cavallaro

Mody

et al. 2016

Nanomaterials

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Bovine anaplasmosis or cattle-tick fever is a tick-borne haemolytic disease caused by the rickettsial haemoparasite Anaplasma marginale in tropical and subtropical areas of the world. While difficult to express, the proteins VirB9-1 and VirB10 are immunogenic components of the outer membrane type IV secretion system that have been identified as candidate antigens for vaccines targeting of A. marginale. Soluble VirB9-1 and VirB10 were successfully expressed using Pichia pastoris. When formulated with the self-adjuvanting silica vesicles, SV-100 (diameter: 50 nm, and pore entrance size: 6 nm), 200 µg of VirB9-1 and VirB10 were adsorbed per milligram of nanoparticle. The VirB9-1 and VirB10, SV-100 formulations were shown to induce higher antibody responses in mice compared to the QuilA formulations. Moreover, intracellular staining of selected cytokines demonstrated that both VirB9-1 and VirB10 formulations induced cell-mediated immune responses in mice. Importantly, the SV-100 VirB9-1 and VirB10 complexes were shown to specifically stimulate bovine T-cell linages derived from calves immunised with A. marginale outer membrane fractions, suggesting formulations will be useful for bovine immunisation and protection studies. Overall this study demonstrates the potential of self-adjuvanting silica vesicle formulations to address current deficiencies in vaccine delivery applications.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nanoparticle-Based Delivery of Anaplasma marginale Membrane Proteins; VirB9-1 and VirB10 Produced in the Pichia pastoris Expression System

Zhang¹,

Cavallaro

Mody

et al. 2016

Nanomaterials

Self Cite

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“…Loading immune modulating molecules into those materials can protect the molecules from rapid removal and degradation in the body and allow favorable delivery of molecules to target sites such as lymph nodes, immune cells, and tumor sites, which lead to the enhanced therapeutic efficacy of materials‐based immunotherapy. Several types of engineered immunomodulatory materials have been developed and their immunomodulatory effects have been demonstrated in diverse platforms, such as poly(lactide‐ co ‐glycolide) (PLG) nanoparticles, PLG scaffolds, carbon‐based nanoparticles, gold nanoparticles, liposomes, mesoporous silica, and other materials …”

Section: Introductionmentioning

confidence: 99%

Mesoporous Silica as a Versatile Platform for Cancer Immunotherapy

2018

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Immunotherapy has been recognized for decades as a promising therapeutic method for cancer treatment. To enhance host immune responses against cancer, antigen‐presenting cells (APCs; e.g., dendritic cells) or T cells are educated using immunomodulatory agents including tumor‐associated antigens and adjuvants, and manipulated to induce a cascading adaptive immune response targeting tumor cells. Mesoporous silica materials are promising candidates to improve cancer immunotherapy based on their attractive properties that include high porosity, high biocompatibility, facile surface modification, and self‐adjuvanticity. Here, the recent progress on mesoporous‐silica‐based immunotherapies based on two material forms is summarized: 1) mesoporous silica nanoparticles (MSNs), which can be internalized into APCs, and 2) micrometer‐sized mesoporous silica rods (MSRs) that can form a 3D space to recruit APCs. Subcutaneously injected MSN‐based cancer vaccines can be taken up by peripheral APCs or by APCs in lymphoid organs to educate the immune system against cancer cells. MSR cancer vaccines can recruit immune cells into the MSR scaffold to induce cancer‐specific immunity. Both vaccine systems successfully stimulate the adaptive immune response to eradicate cancer in vivo. Thus, mesoporous silica has potential value as a material platform for the treatment of cancer or infectious diseases.

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Understanding the Effect of Surface Chemistry of Mesoporous Silica Nanorods on Their Vaccine Adjuvant Potency

Yang

Jambhrunkar

Abbaraju

et al. 2017

Adv Healthcare Materials

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Mesoporous silica nanoparticles are reported as adjuvants in nanovaccines in generating robust antigen-specific immunity. However, the effect of surface chemistry in initiating and modulating the immune response remains largely unexplored. In this study, mesoporous silica nanorods (MSNRs) are modified with NH and C groups to investigate the influence of surface functional groups (OH, NH , and C ) on their adjuvant efficacy. It is found that compared to OH and NH groups, the hydrophobic C modification significantly enhances antigen uptake by antigen presenting cells and endosomal-lysosomal escape in vitro, dendritic cells, and macrophages maturation ex vivo, and elicits secretion of interferon-γ level and antibody response in immunized mice. Moreover, bare MSNR and MSNRNH exhibit T-helper 2 biased immune response, while MSNRC shows a T-helper 1 biased immune response. These findings suggest that the surface chemistry of nanostructured adjuvants has profound impact on the immune response, which provides useful guidance for the design of effective nanomaterial based vaccines.

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Silica vesicles as nanocarriers and adjuvants for generating both antibody and T-cell mediated immune resposes to Bovine Viral Diarrhoea Virus E2 protein

Cited by 39 publications

References 66 publications

Nanoparticle-Based Delivery of Anaplasma marginale Membrane Proteins; VirB9-1 and VirB10 Produced in the Pichia pastoris Expression System

Nanoparticle-Based Delivery of Anaplasma marginale Membrane Proteins; VirB9-1 and VirB10 Produced in the Pichia pastoris Expression System

Mesoporous Silica as a Versatile Platform for Cancer Immunotherapy

Understanding the Effect of Surface Chemistry of Mesoporous Silica Nanorods on Their Vaccine Adjuvant Potency

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