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      Biodegradable Polymeric Nanoparticles-Based Vaccine Adjuvants for Lymph Nodes Targeting

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          Abstract

          Vaccines have successfully eradicated a large number of diseases. However, some infectious diseases (such as HIV, Chlamydia trachomatis or Bacillus anthracis) keep spreading since there is no vaccine to prevent them. One way to overcome this issue is the development of new adjuvant formulations which are able to induce the appropriate immune response without sacrificing safety. Lymph nodes are the site of lymphocyte priming by antigen-presenting cells and subsequent adaptive immune response, and are a promising target for vaccine formulations. In this review, we describe the properties of different polymer-based (e.g., poly lactic-co-glycolic acid, poly lactic acid …) particulate adjuvants as innovative systems, capable of co-delivering immunopotentiators and antigens. We point out how these nanoparticles enhance the delivery of antigens, and how their physicochemical properties modify their uptake by antigen-presenting cells and their migration into lymph nodes. We describe why polymeric nanoparticles increase the persistence into lymph nodes and promote a mature immune response. We also emphasize how nanodelivery directs the response to a specific antigen and allows the induction of a cytotoxic immune response, essential for the fight against intracellular pathogens or cancer. Finally, we highlight the interest of the association between polymer-based vaccines and immunopotentiators, which can potentiate the effect of the molecule by directing it to the appropriate compartment and reducing its toxicity.

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          Most cited references65

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          Role of target geometry in phagocytosis.

          Phagocytosis is a principal component of the body's innate immunity in which macrophages internalize targets in an actin-dependent manner. Targets vary widely in shape and size and include particles such as pathogens and senescent cells. Despite considerable progress in understanding this complicated process, the role of target geometry in phagocytosis has remained elusive. Previous studies on phagocytosis have been performed using spherical targets, thereby overlooking the role of particle shape. Using polystyrene particles of various sizes and shapes, we studied phagocytosis by alveolar macrophages. We report a surprising finding that particle shape, not size, plays a dominant role in phagocytosis. All shapes were capable of initiating phagocytosis in at least one orientation. However, the local particle shape, measured by tangent angles, at the point of initial contact dictates whether macrophages initiate phagocytosis or simply spread on particles. The local shape determines the complexity of the actin structure that must be created to initiate phagocytosis and allow the membrane to move over the particle. Failure to create the required actin structure results in simple spreading and not internalization. Particle size primarily impacts the completion of phagocytosis in cases where particle volume exceeds the cell volume.
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            Phylogenetic perspectives in innate immunity.

            The concept of innate immunity refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms. Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity.
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              Nanoparticle vaccines.

              Nanotechnology increasingly plays a significant role in vaccine development. As vaccine development orientates toward less immunogenic "minimalist" compositions, formulations that boost antigen effectiveness are increasingly needed. The use of nanoparticles in vaccine formulations allows not only improved antigen stability and immunogenicity, but also targeted delivery and slow release. A number of nanoparticle vaccines varying in composition, size, shape, and surface properties have been approved for human use and the number of candidates is increasing. However, challenges remain due to a lack of fundamental understanding regarding the in vivo behavior of nanoparticles, which can operate as either a delivery system to enhance antigen processing and/or as an immunostimulant adjuvant to activate or enhance immunity. This review provides a broad overview of recent advances in prophylactic nanovaccinology. Types of nanoparticles used are outlined and their interaction with immune cells and the biosystem are discussed. Increased knowledge and fundamental understanding of nanoparticle mechanism of action in both immunostimulatory and delivery modes, and better understanding of in vivo biodistribution and fate, are urgently required, and will accelerate the rational design of nanoparticle-containing vaccines. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Vaccines (Basel)
                Vaccines (Basel)
                vaccines
                Vaccines
                MDPI
                2076-393X
                12 October 2016
                December 2016
                : 4
                : 4
                : 34
                Affiliations
                [1 ]Laboratoire de Biologie Tissulaire et d’Ingénierie Thérapeutique, UMR 5305, Université Lyon 1, CNRS, IBCP, Lyon 69007, France; alice.gutjahr@ 123456ibcp.fr (A.G.); capucine.phelip@ 123456ibcp.fr (C.P.); anne-line.coolen@ 123456ibcp.fr (A.-L.C.); clairemonge.biotech@ 123456gmail.com (C.M.); anne-sophie.boisgard@ 123456ibcp.fr (A.-S.B.)
                [2 ]InvivoGen, Toulouse 31400, France
                [3 ]Groupe Immunité des Muqueuses et Agents Pathogènes, INSERM CIC1408 Vaccinologie, Faculté de Médecine de Saint-Etienne, Saint-Etienne 42270, France; stephane.paul@ 123456chu-st-etienne.fr
                Author notes
                [* ]Correspondence: bernard.verrier@ 123456ibcp.fr
                [†]

                These authors contributed equally to this work.

                Article
                vaccines-04-00034
                10.3390/vaccines4040034
                5192354
                27754314
                7e974aae-b8d6-428e-84b5-cb5224cd488a
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 August 2016
                : 29 September 2016
                Categories
                Review

                vaccine,adjuvant,immunogenicity,polymer,nanoparticles,nanodelivery,lymph node,antigen,molecular adjuvant

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