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      Immunogenicity of anthrax recombinant peptides and killed spores in goats and protective efficacy of immune sera in A/J mouse model

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          Abstract

          Anthrax is primarily recognized as an affliction of herbivores with incubation period ranging from three to five days post-infection. Currently, the Sterne live-spore vaccine is the only vaccine approved for control of the disease in susceptible animals. While largely effective, the Sterne vaccine has several problems including adverse reactions in sensitive species, ineffectiveness in active outbreaks and incompatibility with antibiotics. These can be surmounted with the advent of recombinant peptides (non-living) next generation vaccines. The candidate vaccine antigens comprised of recombinant protective antigen (PA), spore-specific antigen (bacillus collagen-like protein of anthracis, BclA) and formaldehyde inactivated spores (FIS). Presently, little information exists on the protectivity of these novel vaccine candidates in susceptible ruminants. Thus, this study sought to assess the immunogenicity of these vaccine candidates in goats and evaluate their protectivity using an in vivo mouse model. Goats receiving a combination of PA, BclA and FIS yielded the highest antibody and toxin neutralizing titres compared to recombinant peptides alone. This was also reflected in the passive immunization experiment whereby mice receiving immune sera from goats vaccinated with the antigen combination had higher survival post-challenge. In conclusion, the current data indicate promising potential for further development of non-living anthrax vaccines in ruminants.

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          Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process.

          Anthrax lethal toxin, which consists of two proteins, protective antigen and lethal factor, is lethal for experimental animals. This study describes the first in vitro system demonstrating lethality of the toxin. Mouse peritoneal macrophages are killed within 1 h of exposure to the toxin. Neither protein component alone shows any toxic activity. The minimal effective concentration of protective antigen and lethal factor was approximately equal to 10(-2) and approximately equal to 10(-3) micrograms/ml, respectively. None of the several established cell lines examined was killed. Cells could be completely protected from the toxin by pretreatment with agents, such as amines or monensin, which dissipate intracellular proton gradients and raise the pH of intracellular vesicles. This protection was reversible and could be overcome by lowering the intravesicular pH. Antitoxin added after preincubation with amines was unable to protect cells subsequently exposed to low pH treatment. These results suggest that anthrax lethal toxin requires passage through an acidic endocytic vesicle in order to exert its toxic effect within the cytosol.
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            Anthrax and wildlife

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              Anthrax vaccines: past, present and future

              Most livestock vaccines in use throughout the world today for immunization against anthrax are derivatives of the live spore vaccine formulated by Sterne in 1937 and still use descendants of his strain 34F2. Credit belongs to this formulation for effective control in many countries with considerable reduction, sometimes complete elimination, of the disease in animals and, since man generally acquires it from livestock, in man also. However, there are some contraindications of its use and situations in which it cannot be easily administered, and room for development of a successor is discussed. The human vaccines, formulated for at-risk occupations and situations, date from the 1950s (UK vaccine) and 1960s (US vaccine). The rather greater need for improvement of these as compared with the veterinary vaccine stimulated valuable research during the 1980s which has led to a number of promising candidate alternatives for the future.
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                Author and article information

                Contributors
                okechukwu.ndumnego@ahri.org
                Henriette.VanHeerden@up.ac.za
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                16 November 2018
                16 November 2018
                2018
                : 8
                : 16937
                Affiliations
                [1 ]ISNI 0000 0001 2107 2298, GRID grid.49697.35, Department of Veterinary Tropical Diseases, , University of Pretoria, ; Onderstepoort, South Africa
                [2 ]ISNI 0000 0001 2290 1502, GRID grid.9464.f, Institute of Animal Science, Department of Livestock Infectiology and Environmental Hygiene, , University of Hohenheim, ; Stuttgart, Germany
                [3 ]GRID grid.488675.0, Present Address: Africa Health Research Institute, ; Durban, South Africa
                [4 ]ISNI 0000 0001 0940 3744, GRID grid.13652.33, Present Address: Robert Koch Institute, ; Berlin, Germany
                Author information
                http://orcid.org/0000-0003-2958-7151
                Article
                35382
                10.1038/s41598-018-35382-8
                6240085
                30446695
                b9c9a7d0-d6ba-4da3-a298-b8be1bb69d44
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 June 2018
                : 2 November 2018
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