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WIREs Nanomed Nanobiotechnol
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Biomaterials and nanomaterials for sustained release vaccine delivery

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Abstract Vaccines are considered one of the most significant medical advancements in human history, as they have prevented hundreds of millions of deaths since their discovery; however, modern travel permits disease spread at unprecedented rates, and vaccine shortcomings like thermal sensitivity and required booster shots have been made evident by the COVID‐19 pandemic. Approaches to overcoming these issues appear promising via the integration of vaccine technology with biomaterials, which offer sustained‐release properties and preserve proteins, prevent conformational changes, and enable storage at room temperature. Sustained release and thermal stabilization of therapeutic biomacromolecules is an emerging area that integrates material science, chemistry, immunology, nanotechnology, and pathology to investigate different biocompatible materials. Biomaterials, including natural sugar polymers, synthetic polyesters produced from biologically derived monomers, hydrogel blends, protein–polymer blends, and metal–organic frameworks, have emerged as early players in the field. This overview will focus on significant advances of sustained release biomaterial in the context of vaccines against infectious disease and the progress made towards thermally stable “single‐shot” formulations. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease
A pie chart showing in percentages the (a) leading causes of death worldwide and (b) the number of deaths by the leading causes of deaths by infectious diseases for 2017. The number of publications published from 1995 to 2021 with the keyword being (c) vaccine refined to journals, letters, and reports, with additional refinement for in vivo and (d) polymer vaccine or sustained release vaccine refined to journals, letters, and reports, explicitly regarding in vivo work. Note: 2021 publications were checked on April 25, 2021
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The Cevhar lab investigates chitosan activation of the immune system when different administrations are used and compare the cytokine production of (a) IL‐2, (b) IL‐4, (c) IL‐6, (d) IL‐10, and (e) IFN‐γ. . (Reprinted with permission from Sinani et al. (2019). Copyright 2019 Elsevier). (f) the Han lab vaccinated mice with PLGA containing a subunit protein CAMP found in toxoplasma gondii, which improve the survival rate of mice compared to a bolus shot of the subunit protein alone. (Reprinted with permission from G. Liu et al. (2017). Copyright 2017 Elsevier)
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(a) The comparison of ovalbumin antibodies that have been encapsulated inside of a cubosome polymer with and without adjuvant has similar production compared to alum. (Reprinted with permission from Rizwan et al. (2013). Copyright 2013 Elsevier). An image of a (b) the steps to develop silk loaded microneedle tips, containing HIV trimer along with adjuvants and when delivered into mice models, (c) the microneedle containing trimer and adjuvant produced the highest amount of antibodies. (Reprinted with permission from Boopathy et al. (2019). Copyright 2019 PNAS). (d) The Xu lab shows that chitosan nanoparticles have a higher upregulation in CD40, CD80, and CD86 in bone marrow dendritic cells compared to a bolus shot of the hepatitis B antigen. (Reprinted with permission from Z.‐B. Wang et al. (2016). Copyright 2016 Royal Society of Chemistry). The Fahmy lab compares the slow release of PLGA, liposome, and alum for release of ovalbumin and show that PLGA stimulates a higher population of cytotoxic T cells producing (e) IFN‐γ and (f) activated specifically to ovalbumin. (Reprinted with permission from Demento et al., 2012. Copyright 2012 Elsevier)
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A schematic of different ways biomaterials interact with antigens. Each approach has focused to improve delivery of the antigens in order to enhance the immune response. Encapsulation and infiltration have been more heavily investigated owing to the potential stability they offer to the antigens trapped within. Created with BioRender.com
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(a) Cartoon illustration of the construction of a ZIF‐8. (b) Crystal structure of ZIF‐8 showing cage and pores in the extended lattice and how they are connected by zinc and imidazole. (c) Conceptualization of the synthesis and product of a biomimetic mineralization process where the viral proteins from tobacco mosaic virus (TMV) triggers the growth and then results in its entrapment inside the framework ([email protected])
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(a) The Appel lab formulated different hydrogels to tune the release and determine the activation of the germinal center in the draining lymph node. (Reprinted with permission from Roth et al. (2020). Copyright 2020 American Chemical Society). (b) Coprecipitation begins by adding ovalbumin into water containing PVP. Zinc and 2‐methylimidazole in methanol are mixed together and placed in an ultrasonic bath for 10 min to react. After 10 min, PVP + ovalbumin is added and sonicated for an additional 3 min. The resulting solution is washed with methanol and centrifuged—The washing is done three times. CpG is later mixed and adsorbs to the surface to make [email protected]‐8‐CpG. (Reprinted with permission from Y. Zhang et al. (2016b). Copyright 2016 John Wiley and Sons)
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The Xu lab investigate chitosan with antigen to evaluate it as a potential adjuvant and determine the mechanism of immune activation. (Reprinted with permission from Z.‐B. Wang et al. (2016). Copyright 2016 Royal Society of Chemistry)
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Chemical structures of commonly used polysaccharides in pre‐clinical vaccines
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SEM images of different PLGA particle sizes tested by the Ma lab to determine the effects it has on activating the immune system. (Reprinted with permission from Jia et al. (2017). Copyright 2017 American Chemical Society)
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Chemical structures of commonly used synthetic biodegradable polymers used in vaccines
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