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      Evaluation of Immunoprotective Effects of Fusobacterium necrophorum Outer Membrane Proteins 43K OMP, Leukotoxin and Hemolysin Multi-Component Recombinant Subunit Vaccine in Mice

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          Abstract

          We evaluated the efficacy of three vaccine formulations containing different combinations of proteins (43K OMP, leukotoxin recombinant protein PL4 and hemolysin recombinant protein H2) and killed whole cell Fusobacterium necrophorum in preventing liver abscess. Four subcutaneous vaccines were formulated: vaccine 1 (43K OMP), vaccine 2 (PL4 and H2), vaccine 3 (43K OMP, PL4 and H2), and vaccine 4 (killed whole bacterial cell). 43K OMP, PL4, and H2 proteins were produced by using recombinant protein expression. To evaluate vaccine efficacy, we randomly allocated 50 BALB/c female mice to one of five different treatment groups: PBS control group, vaccine 1, vaccine 2, vaccine 3, and vaccine 4. Mice were vaccinated three times, with 14 days between each immunization. After immunization, the mice were challenged with F. necrophorum. The three key findings of this study are as follows: (1) Vaccine 3 has enabled mice to produce higher antibody titer following bacterial challenge, (2) in the liver pathology of mice, the vaccine 3 liver showed the least pathology, and (3) all four vaccines produced high levels of antibodies and cytokines in mice, but the level of vaccine 3 was the highest. Based on our results, it has been demonstrated that a mixture of F. necrophorum 43K OMP, PL4, and H2 proteins inoculated with mice can achieve protection against liver abscess in mice. Our research may therefore provide the basis for the development of a vaccine against F. necrophorum bovine infections.

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          The regulation of IL-10 production by immune cells.

          Interleukin-10 (IL-10), a cytokine with anti-inflammatory properties, has a central role in infection by limiting the immune response to pathogens and thereby preventing damage to the host. Recently, an increasing interest in how IL10 expression is regulated in different immune cells has revealed some of the molecular mechanisms involved at the levels of signal transduction, epigenetics, transcription factor binding and gene activation. Understanding the specific molecular events that regulate the production of IL-10 will help to answer the remaining questions that are important for the design of new strategies of immune intervention.
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            The role of interleukin-2 during homeostasis and activation of the immune system.

            Interleukin-2 (IL-2) signals influence various lymphocyte subsets during differentiation, immune responses and homeostasis. As discussed in this Review, stimulation with IL-2 is crucial for the maintenance of regulatory T (T(Reg)) cells and for the differentiation of CD4(+) T cells into defined effector T cell subsets following antigen-mediated activation. For CD8(+) T cells, IL-2 signals optimize both effector T cell generation and differentiation into memory cells. IL-2 is presented in soluble form or bound to dendritic cells and the extracellular matrix. Use of IL-2 - either alone or in complex with particular neutralizing IL-2-specific antibodies - can amplify CD8(+) T cell responses or induce the expansion of the T(Reg) cell population, thus favouring either immune stimulation or suppression.
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              Selective stimulation of T cell subsets with antibody-cytokine immune complexes.

              Interleukin-2 (IL-2), which is a growth factor for T lymphocytes, can also sometimes be inhibitory. Thus, the proliferation of CD8+ T cells in vivo is increased after the injection of a monoclonal antibody that is specific for IL-2 (IL-2 mAb), perhaps reflecting the removal of IL-2-dependent CD4+ T regulatory cells (T regs). Instead, we show here that IL-2 mAb augments the proliferation of CD8+ cells in mice simply by increasing the biological activity of preexisting IL-2 through the formation of immune complexes. When coupled with recombinant IL-2, some IL-2/IL-2 mAb complexes cause massive (>100-fold) expansion of CD8+ cells in vivo, whereas others selectively stimulate CD4+ T regs. Thus, different cytokine-antibody complexes can be used to selectively boost or inhibit the immune response.
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                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                06 December 2021
                2021
                : 8
                : 780377
                Affiliations
                Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University , Daqing, China
                Author notes

                Edited by: Massimo Amadori, Italian Network of Veterinary Immunology, Italy

                Reviewed by: T. G. Nagaraja, Kansas State University, United States; Raghavendra G. Amachawadi, Kansas State University, United States

                *Correspondence: Donghua Guo dh_guo@ 123456126.com

                This article was submitted to Veterinary Infectious Diseases, a section of the journal Frontiers in Veterinary Science

                †These authors have contributed equally to this work

                Article
                10.3389/fvets.2021.780377
                8685265
                7cca0454-df75-4376-8aa4-d00ff1bee506
                Copyright © 2021 Xiao, Jiang, He, Zhang, Wang, Wang, Wang and Guo.

                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(s) 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
                : 21 September 2021
                : 10 November 2021
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 47, Pages: 9, Words: 5994
                Categories
                Veterinary Science
                Original Research

                43k omp,hemolysin,leukotoxin,immunoprotective,fusobacterium necrophorum

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