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      Vaccination of Mice with Virulence-Associated Protein G (VapG) Antigen Confers Partial Protection against Rhodococcus equi Infection through Induced Humoral Immunity

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          Abstract

          Rhodococcus equi is a facultative intracellular bacterium causing severe pyogranulomatous pneumonia, ulcerative enterocolitis, and mesenteric lymphadenopathy in foals aged less than 6 months. Less frequently, this pathogen affects various other species, such as pigs, cattle, cats, and even humans. Although rhodococcosis is treated with a combination of antimicrobial agents, resistance is developed in some cases, and thus, antimicrobial susceptibility must be monitored and managed. Considering these limitations of the current therapy and unavailability of a vaccine to prevent the disease, research is particularly focused on the development of an effective vaccine against rhodococcosis. Most vaccines undergoing development utilize the virulence-associated protein (Vap) A antigen, which was identified previously as a key virulence factor of R. equi. Nevertheless, other proteins, such as VapG, present in most virulent R. equi strains, are also encoded by vap genes located on the R. equi bacterial virulence plasmid. In the present study, we evaluated the effect of VapG immunization on the survival of R. equi-challenged mice. We used attenuated Salmonella as a carrier for VapG ( Salmonella- vapG+), a procedure previously adopted to develop a VapA-based vaccine. We observed that vaccination with Salmonella- vapG+ induced both an increased IFN-γ, IL-12, and TNF-α production, and a decreased bacterial burden in organs of the R. equi-challenged mice. Nevertheless, Salmonella- vapG+ vaccination protected only 50% of the mice challenged with a lethal dose of R. equi. Interestingly, we observed an increased frequency of B cells in the spleen of Salmonella- vapG+-vaccinated mice and showed that Salmonella- vapG+-vaccinated R. equi-challenged B-cell-knockout mice did not reduce the bacterial burden. Given these results, we discussed the potential role of the humoral immune response induced by Salmonella- vapG+ vaccination in conferring protection against R. equi infection, as well as the employment of VapG antigen for obtaining hyperimmune plasma to prevent rhodoccocosis in young foals.

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          Most cited references34

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          Nonparametric Estimation from Incomplete Observations

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            A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene.

            Of the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu chain), but not light chains. Recent data suggest that pre-B cells express mu chains on the membrane together with the 'surrogate' light chains lambda 5 and V pre B (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes. We have now assessed the importance of the membrane form of the mu chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting in mouse embryonic stem cells. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation.
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              Rhodococcus equi infection.

              Rhodococcus equi is a veterinary pathogen that can cause substantial morbidity in patients that are immunocompromised and are occupationally and recreationally exposed to farming, livestock, and dry soil environments. Although the clinical spectrum of disease associated with R equi is broad, pulmonary involvement is a predominant feature in most cases. We present a case of occupationally acquired R equi pneumonia and mediastinal lymphadenitis in a patient that has had a renal transplant and is in receipt of a stable immunosuppression regimen. We review the pathogenesis and clinical characteristics of infections with Rhodococcus spp, and discuss approaches to treatment of this disease entity in populations of patients who are immunocompromised. Copyright 2010 Elsevier Ltd. All rights reserved.
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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
                11 May 2017
                2017
                : 8
                : 857
                Affiliations
                Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo São Paulo, Brazil
                Author notes

                Edited by: Kuldeep Dhama, Indian Veterinary Research Institute, India

                Reviewed by: Sandip Kumar Khurana, National Research Centre on Equines, India; Muhammad Zubair Shabbir, University of Veterinary and Animal Sciences, Pakistan

                *Correspondence: Sandro G. Soares, soares@ 123456fmrp.usp.br

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

                Article
                10.3389/fmicb.2017.00857
                5425581
                28553279
                93be0424-06ad-4778-88ca-e6ed2398259f
                Copyright © 2017 Trevisani, Hanna, Oliveira, Cardoso, Roque-Barreira and Soares.

                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
                : 18 February 2017
                : 27 April 2017
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 35, Pages: 9, Words: 0
                Funding
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo 10.13039/501100001807
                Award ID: 06/60941-0
                Award ID: 09/53720-5
                Award ID: 08/57354-0
                Award ID: 08/50602-9
                Award ID: 13/24201-5
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 10.13039/501100003593
                Award ID: 555256/2010-3
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 10.13039/501100002322
                Award ID: PROEX
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                rhodococcus equi,vectored vaccine,vapg,aptx,attenuated salmonella
                Microbiology & Virology
                rhodococcus equi, vectored vaccine, vapg, aptx, attenuated salmonella

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