Conjugation to Nickel-Chelating Nanolipoprotein Particles Increases the Potency and Efficacy of Subunit Vaccines to Prevent West Nile Encephalitis

Fischer, Nicholas O.; Infante, Ernesto; Ishikawa, Takahiro; Blanchette, Craig D.; Bourne, Nigel; Hoeprich, Paul D.; Mason, Peter W.

doi:10.1021/bc100083d

Cited by 39 publications

(36 citation statements)

References 46 publications

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“…Although we demonstrated the potential of attaching multiple different types of biological molecules using NLPs of varying composition and functional anchors, the NiNLP (35% NiLipid and 65% DOPC) was selected for further analysis of in vitro cytotoxicity, in vivo toxicity, in vivo immunogenicity and in vivo biodistribution as the NiNLP has been previously utilized as an in vivo antigen delivery vehicle for vaccine applications [32] and is one of the most versatile functional NLPs for use in delivery of any His-tagged protein [34], [37].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform

et al. 2014

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Nanoparticles hold great promise for the delivery of therapeutics, yet limitations remain with regards to the use of these nanosystems for efficient long-lasting targeted delivery of therapeutics, including imparting functionality to the platform, in vivo stability, drug entrapment efficiency and toxicity. To begin to address these limitations, we evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high-density lipoproteins (HDLs). We found that a wide range of molecules could be reliably conjugated to the NLP, including proteins, single-stranded DNA, and small molecules. The NLP was also found to be relatively stable in complex biological fluids and displayed no cytotoxicity in vitro at doses as high as 320 µg/ml. In addition, we observed that in vivo administration of the NLP daily for 14 consecutive days did not induce significant weight loss or result in lesions on excised organs. Furthermore, the NLPs did not display overt immunogenicity with respect to antibody generation. Finally, the biodistribution of the NLP in vivo was found to be highly dependent on the route of administration, where intranasal administration resulted in prolonged retention in the lung tissue. Although only a select number of NLP compositions were evaluated, the findings of this study suggest that the NLP platform holds promise for use as both a targeted and non-targeted in vivo delivery vehicle for a range of therapeutics.

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Section: Resultsmentioning

confidence: 99%

Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform

et al. 2014

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“…Several vaccines, such as the hepatitis B vaccine and the human papilloma virus vaccine, have already been developed utilizing these platforms (16, 17). Other examples of experimental use of particles for vaccine delivery are the self‐assembling polypeptide‐based nanoparticles (SAPNs) for peptide sporozoite malaria vaccine (18), nanolipoproteins for vaccines against West Nile encephalitis (19), and poly(propylene sulfide) nanoparticles for intranasal delivery of peptide antigens to enhance mucosal immune responses (20). A recent immunogenicity study of a malaria circumsporozoite peptide epitope vaccine, presented on self‐assembling peptide nanofibers, shows promising results in developing the nanofibers as a multi‐epitopes vaccine platform (21).…”

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confidence: 99%

Iron oxide nanoparticles as a clinically acceptable delivery platform for a recombinant blood‐stage human malaria vaccine

et al. 2012

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This study explored the novel use of iron oxide (IO) nanoparticles (<20 nm) as a vaccine delivery platform without additional adjuvants. A recombinant malaria vaccine antigen, the merozoite surface protein 1 (rMSP1), was conjugated to IO nanoparticles (rMSP1-IO). Immunizations in outbred mice with rMSP1-IO achieved 100% responsiveness with antibody titers comparable to those obtained with rMSP1 formulated with a clinically acceptable adjuvant, Montanide ISA51 (2.7×10 vs. 1.6×10; respectively). Only rMSP1-1O could induce significant levels (80%) of parasite inhibitory antibodies. The rMSP1-IO was highly stable at 4°C and was amenable to lyophilization, maintaining its antigenicity, immunogenicity, and ability to induce inhibitory antibodies. Further testing in nonhuman primates, Aotus monkeys, also elicited 100% immune responsiveness and high levels of parasite inhibitory antibodies (55-100% inhibition). No apparent local or systemic toxicity was associated with IO immunizations. Murine macrophages and dendritic cells efficiently (>90%) internalized IO nanoparticles, but only the latter were significantly activated, with elevated expression/secretion of CD86, cytokines (IL-6, TNF-α, IL1-b, IFN-γ, and IL-12), and chemokines (CXCL1, CXCL2, CCL2, CCL3, CCL4, and CXCL10). Thus, the IO nanoparticles is a novel, safe, and effective vaccine platform, with built-in adjuvancy, that is highly stable and field deployable for cost-effective vaccine delivery.

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“…However, these traditional vaccines present challenges in terms of safety, residual toxicity, means of transportation, and difficulties associated with sufficient mass production. A subunit vaccine based on protective vaccine antigen epitopes enables investigators to overcome the problems of conventional vaccines and provides a safer, more cost-effective approach to vaccine development [10]. …”

Section: Introductionmentioning

confidence: 99%

Protective Immunity against Trichinella spiralis Infection Induced by a Multi-Epitope Vaccine in a Murine Model

Wei

Yang

et al. 2013

PLoS ONE

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Trichinellosis is one of the most important food-borne parasitic zoonoses throughout the world. Because infected pigs are the major source of human infections, and China is becoming the largest international producer of pork, the development of a transmission-blocking vaccine to prevent swine from being infected is urgently needed for trichinellosis control in China. Our previous studies have demonstrated that specific Trichinella spiralis paramyosin (Ts-Pmy) and Ts-87 antigen could provide protective immunity against T. spiralis infection in immunized mice. Certain protective epitopes of Ts-Pmy and Ts-87 antigen have been identified. To identify more Ts-Pmy protective epitopes, a new monoclonal antibody, termed 8F12, was produced against the N-terminus of Ts-Pmy. This antibody elicited significant protective immunity in mice against T. spiralis infection by passive transfer and was subsequently used to screen a random phage display peptide library to identify recognized epitopes. Seven distinct positive phage clones were identified and their displayed peptides were sequenced. Synthesized epitope peptides conjugated to keyhole limpet hemocyanin were used to immunize mice, four of which exhibited larval reduction (from 18.7% to 26.3%, respectively) in vaccinated mice in comparison to the KLH control. To increase more effective protection, the epitope 8F7 that was found to induce the highest protection in this study was combined with two other previously identified epitopes (YX1 from Ts-Pmy and M7 from Ts-87) to formulate a multi-epitope vaccine. Mice immunized with this multi-epitope vaccine experienced a 35.0% reduction in muscle larvae burden after being challenged with T. spiralis larvae. This protection is significantly higher than that induced by individual-epitope peptides and is associated with high levels of subclasses IgG and IgG1. These results showed that a multi-epitope vaccine induced better protective immunity than an individual epitope and provided a feasible approach for developing a safer and more effective vaccine against trichinellosis.

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Conjugation to Nickel-Chelating Nanolipoprotein Particles Increases the Potency and Efficacy of Subunit Vaccines to Prevent West Nile Encephalitis

Cited by 39 publications

References 46 publications

Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform

Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform

Iron oxide nanoparticles as a clinically acceptable delivery platform for a recombinant blood‐stage human malaria vaccine

Protective Immunity against Trichinella spiralis Infection Induced by a Multi-Epitope Vaccine in a Murine Model

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