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WIREs Nanomed Nanobiotechnol
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Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

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Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen‐based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co‐delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens. WIREs Nanomed Nanobiotechnol 2017, 9:e1403. doi: 10.1002/wnan.1403 This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
A nanoemulsion (NE) system formulated with the anthrax protective antigen (PA) enhanced mucosal humoral immune responses and improved protection against bacterial spore challenges. Compared with conventional adjuvants, such as monophosphoryl lipid A (MPLA), CpG, and aluminum hydroxide, the NE vaccine administered via the intranasal route elicited higher titers of anti‐PA IgA (a) and IgG (b) in bronchial alveolar lavage fluids from immunized mice. Vaccination with the NE vaccine also protected guinea pigs against an intranasal challenge with a 10‐fold (c) or 100‐fold (d) LD50 dose of bacterial spores. (Reprinted with permission from Ref . Copyright 2007 American Society for Microbiology)
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Erythrocyte membrane‐coated poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles for vaccine delivery of staphylococcal α‐hemolysin (Hla). (a) Schematic illustration and an image by transmission electron microscope of the nanotoxoid. Scale bar: 80 nm. (b) The nanotoxoid vaccine enhanced humoral immune responses and protected mice against toxin challenge. Empty triangles, vaccine particles without the antigen; solid triangles, unvaccinated control; blue squares, single dose of the heat‐inactivated Hla; blue spheres, single dose of the nanotoxoid; red squares, three doses of the heat‐inactivated Hla; red spheres, three doses of the nanotoxoid. (Reprinted with permission from Ref . Copyright 2013 Nature Publishing Group)
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A cationic nanogel developed for intranasal delivery of a subunit botulism neurotoxin. (a) The nanogel was self‐assembled by the polysaccharide pullulan modified with cholesteryl and amino groups. Intranasal immunization with antigen‐loaded nanogels significantly enhanced nasal residence of the antigen (b), antigen‐specific antibody titers (c), and protection against challenge with the neurotoxin (d), compared with the soluble antigen. (Reprinted with permission from Ref . Copyright 2010 Nature Publishing Group)
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Virus‐like particles (VLPs) as an Ebola vaccine candidate. (a) Transmission electron microscope images of Ebola viruses (left) and VLPs (right). (b) Mice were immunized three times with Ebola VLPs (eVLPs), inactivated Ebola viruses (iEBOV) or Marburg viruses (iMARV), or phosphate‐buffered saline (PBS), followed by a challenge with the mouse‐adapted Ebola virus. (a and b: Reprinted with permission from Ref . Copyright 2003 National Academy of Sciences, USA) (c) and (d) Humoral and cellular immune responses elicited by Ebola VLPs were augmented by polyI:C. (c) A low dose of VLPs along with 100 ng–100 µg polyI:C elicited high serum titers of antigen‐specific IgG. (d) Splenocytes from immunized mice were cultured with Ebola GP, followed by stimulation with an Ebola GP peptide in vitro. Robust effector T cells were induced by immunization with 10 µg VLPs and polyI:C. (c and d: Reprinted with permission from Ref . Copyright 2014 Public Library of Science)
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Lipid‐based nanoparticles for delivery of subunit plague antigens. (a) A nanolipoprotein particle loaded with adjuvants and the plague low calcium response V (LcrV) antigen modified with poly‐histidine. (b) Co‐delivery of LcrV and adjuvants via the intraperitoneal route elicited higher anti‐LcrV IgG titers than LcrV admixed with or without soluble or particulate adjuvants. (a and b: Reprinted with permission from Ref . Copyright 2013 American Chemical Society). (c) A cationic lipid/hyaluronic acid (HA) hybrid nanoparticle formed by cross‐linking of thiolated HA and thiolated polyethylene glycol (PEG). (d) Intranasal vaccination with the hybrid particles co‐loaded with F1‐V and monophosphoryl lipid A (MPLA) elicited significantly higher serum titers of anti‐F1‐V IgG compared with the soluble mixture of F1‐V and MPLA. (c and d: Reprinted with permission from Ref . Copyright 2015 Elsevier)
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Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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