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      An Overview of Challenges Limiting the Design of Protective Mucosal Vaccines for Finfish

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          Abstract

          Research in mucosal vaccination in finfish has gained prominence in the last decade in pursuit of mucosal vaccines that would lengthen the duration of protective immunity in vaccinated fish. However, injectable vaccines have continued to dominate in the vaccination of finfish because they are perceived to be more protective than mucosal vaccines. Therefore, it has become important to identify the factors that limit developing protective mucosal vaccines in finfish as an overture to identifying key areas that require optimization in mucosal vaccine design. Some of the factors that limit the success for designing protective mucosal vaccines for finfish identified in this review include the lack optimized protective antigen doses for mucosal vaccines, absence of immunostimulants able to enhance the performance of non-replicative mucosal vaccines, reduction of systemic antibodies due to prolonged exposure to oral vaccination and the lack of predefined correlates of protective immunity for use in the optimization of newly developed mucosal vaccines. This review also points out the need to develop prime-boost vaccination regimes able to induce long-term protective immunity in vaccinated fish. By overcoming some of the obstacles identified herein, it is anticipated that future mucosal vaccines shall be designed to induce long-term protective immunity in finfish.

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          The genome sequence of Atlantic cod reveals a unique immune system.

          Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.
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            Vaccines: correlates of vaccine-induced immunity.

            The immune system is redundant, and B and T cells collaborate. However, almost all current vaccines work through induction of antibodies in serum or on mucosa that block infection or interfere with microbial invasion of the bloodstream. To protect, antibodies must be functional in the sense of neutralization or opsonophagocytosis. Correlates of protection after vaccination are sometimes absolute quantities but often are relative, such that most infections are prevented at a particular level of response but some will occur above that level because of a large challenge dose or deficient host factors. There may be >1 correlate of protection for a disease, which we term "cocorrelates." Either effector or central memory may correlate with protection. Cell-mediated immunity also may operate as a correlate or cocorrelate of protection against disease, rather than against infection. In situations where the true correlate of protection is unknown or difficult to measure, surrogate tests (usually antibody measurements) must suffice as predictors of protection by vaccines. Examples of each circumstance are given.
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              The mucosal immune system of fish: the evolution of tolerating commensals while fighting pathogens.

              The field of mucosal immunology research has grown fast over the past few years, and our understanding on how mucosal surfaces respond to complex antigenic cocktails is expanding tremendously. With the advent of new molecular sequencing techniques, it is easier to understand how the immune system of vertebrates is, to a great extent, orchestrated by the complex microbial communities that live in symbiosis with their hosts. The commensal microbiota is now seen as the "extended self" by many scientists. Similarly, fish immunologist are devoting important research efforts to the field of mucosal immunity and commensals. Recent breakthroughs on our understanding of mucosal immune responses in teleost fish open up the potential of teleosts as animal research models for the study of human mucosal diseases. Additionally, this new knowledge places immunologists in a better position to specifically target the fish mucosal immune system while rationally designing mucosal vaccines and other immunotherapies. In this review, an updated view on how teleost skin, gills and gut immune cells and molecules, function in response to pathogens and commensals is provided. Finally, some of the future avenues that the field of fish mucosal immunity may follow in the next years are highlighted. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/77708
                URI : http://frontiersin.org/people/u/238750
                URI : http://frontiersin.org/people/u/198285
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                22 October 2015
                2015
                : 6
                : 542
                Affiliations
                [1] 1Section of Aquatic Medicine and Nutrition, Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences , Oslo, Norway
                Author notes

                Edited by: Jorge Galindo-Villegas, Murcia University, Spain

                Reviewed by: Daniel Barreda, University of Alberta, Canada; Jorge Cuéllar-Anjel, Camaronera de Cocle, Panama

                *Correspondence: Hetron Mweemba Munang’andu, hetroney.mweemba.munangandu@ 123456nmbu.no

                Specialty section: This article was submitted to Immunotherapies and Vaccines, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2015.00542
                4617105
                26557121
                a1305fdf-37dc-4397-990f-1b4a54295a37
                Copyright © 2015 Munang’andu, Mutoloki and Evensen.

                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) or licensor 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
                : 16 May 2015
                : 08 October 2015
                Page count
                Figures: 0, Tables: 4, Equations: 0, References: 114, Pages: 11, Words: 9758
                Categories
                Immunology
                Review

                Immunology
                bath,antigens,finfish,genomics,immersion,mucosal,oral,vaccines
                Immunology
                bath, antigens, finfish, genomics, immersion, mucosal, oral, vaccines

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