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      Outer Membrane Vesicles: Current Status and Future Direction of These Novel Vaccine Adjuvants

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          Abstract

          Adjuvants have been of great interest to vaccine formulation as immune-stimulators. Prior to the recent research in the field of immune stimulation, conventional adjuvants utilized for aluminum-based vaccinations dominated the adjuvant market. However, these conventional adjuvants have demonstrated obvious defects, including poor protective efficiency and potential side effects, which hindered their widespread circulation. Outer membrane vesicles (OMVs) naturally exist in gram-negative bacteria and are capable of engaging innate and adaptive immunity and possess intrinsic adjuvant capacity. They have shown tremendous potential for adjuvant application and have recently been successfully applied in various vaccine platforms. Adjuvants could be highly effective with the introduction of OMVs, providing complete immunity and with the benefits of low toxicity; further, OMVs might also be designed as an advanced mucosal delivery vehicle for use as a vaccine carrier. In this review, we discuss adjuvant development, and provide an overview of novel OMV adjuvants and delivery vehicles. We also suggest future directions for adjuvant research. Overall, we believe that OMV adjuvants would find high value in vaccine formulation in the future.

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          Towards an understanding of the adjuvant action of aluminium.

          The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work.
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            Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus.

            Nanoparticles larger than the reported mesh-pore size range (10-200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (D(eff)) only 4- and 6-fold lower than that for the same particles in water (at time scale tau = 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, D(eff) was 200-fold lower in mucus than in water. For uncoated particles 100-500 nm in diameter, D(eff) was 2,400- to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200- to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery.
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              Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant.

              The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces the need for a new generation of immunostimulatory adjuvants. Because adverse effects are a paramount concern in prophylactic immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned about this compound's mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak version of lipopolysaccharide. Instead, monophosphoryl lipid A's structure seems to have fortuitously retained several functions needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                26 April 2018
                2018
                : 9
                : 783
                Affiliations
                Department of Medical Microbiology, School of Medicine, Nanchang University , Nanchang, China
                Author notes

                Edited by: José Roberto Mineo, Federal University of Uberlandia, Brazil

                Reviewed by: Maryam Dadar, Razi Vaccine and Serum Research Institute, Iran; Sandip Chakraborty, College of Veterinary Sciences and Animal Husbandry, India

                *Correspondence: Qiong Liu p19890528@ 123456126.com

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2018.00783
                5932156
                29755431
                e68749da-8936-415f-a670-40bafb824c8e
                Copyright © 2018 Tan, Li, Huang and Liu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 December 2017
                : 06 April 2018
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 102, Pages: 12, Words: 8922
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 31760261
                Categories
                Microbiology
                Review

                Microbiology & Virology
                outer membrane vesicles (omvs),adjuvants,immunostimulator,vaccine,mucosal delivery carrier

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