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      Immunogenicity and Protective Efficacy of a Non-Living Anthrax Vaccine versus a Live Spore Vaccine with Simultaneous Penicillin-G Treatment in Cattle

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          Abstract

          Sterne live spore vaccine (SLSV) is the current veterinary anthrax vaccine of choice. Unlike the non-living anthrax vaccine (NLAV) prototype, SLSV is incompatible with concurrent antibiotics use in an anthrax outbreak scenario. The NLAV candidates used in this study include a crude recombinant protective antigen (CrPA) and a purified recombinant protective antigen (PrPA) complemented by formalin-inactivated spores and Emulsigen-D ®/Alhydrogel ® adjuvants. Cattle were vaccinated twice (week 0 and 3) with NLAVs plus penicillin-G (Pen-G) treatment and compared to cattle vaccinated twice with SLSV alone and with Pen-G treatment. The immunogenicity was assessed using ELISA against rPA and FIS, toxin neutralisation assay (TNA) and opsonophagocytic assay. The protection was evaluated using an in vivo passive immunisation mouse model. The anti-rPA IgG titres for NLAVs plus Pen-G and SLSV without Pen-G treatment showed a significant increase, whereas the titres for SLSV plus Pen-G were insignificant compared to pre-vaccination values. A similar trend was measured for IgM, IgG1, and IgG2 and TNA titres (NT 50) showed similar trends to anti-rPA titres across all vaccine groups. The anti-FIS IgG and IgM titres increased significantly for all vaccination groups at week 3 and 5 when compared to week 0. The spore opsonising capacity increased significantly in the NLAV vaccinated groups including Pen-G treatment and the SLSV without Pen-G but much less in the SLSV group with Pen-G treatment. Passive immunization of A/J mice challenged with a lethal dose of 34F2 spores indicated significant protective capacity of antibodies raised in the SLSV and the PrPA + FIS + adjuvants vaccinated and Pen-G treated groups but not for the NLAV with the CrPA + FIS + adjuvants and the SLSV vaccinated and Pen-G treated group. Our findings indicate that the PrPA + FIS + Emulsigen-D ®/Alhydrogel ® vaccine candidate may provide the same level of antibody responses and protective capacity as the SLSV. Advantageously, it can be used concurrently with Penicillin-G in an outbreak situation and as prophylactic treatment in feedlots and valuable breeding stocks.

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          Most cited references51

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          Vaccine adjuvants: putting innate immunity to work.

          Adjuvants enhance immunity to vaccines and experimental antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide maximum protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens. Copyright © 2010 Elsevier Inc. All rights reserved.
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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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              Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.

              S H Leppla (1982)
              Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals but in pairs produce two toxic actions. Injection of PA with LF causes death of rats in 60 min, whereas PA with EF causes edema in the skin of rabbits and guinea pigs. The mechanisms of action of these proteins have not been determined. It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] produced by Bacillus anthracis in an inactive form. Activation occurs upon contact with a heat-stable eukaryotic cell material. The specific activity of the resulting adenylate cyclase nearly equals that of the most active known cyclase. In Chinese hamster ovary cells exposed to PA and EF, cAMP concentrations increase without a lag to values about 200-fold above normal, remain high in the continued presence of toxin, and decrease rapidly after its removal. The increase in cAMP is completely blocked by excess LF. It is suggested that PA interacts with cells to form a receptor system by which EF and perhaps LF gain access to the cytoplasm.
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                Author and article information

                Journal
                Vaccines (Basel)
                Vaccines (Basel)
                vaccines
                Vaccines
                MDPI
                2076-393X
                09 October 2020
                December 2020
                : 8
                : 4
                : 595
                Affiliations
                [1 ]Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria 0110, South Africa; henriette.vanheerden@ 123456up.ac.za
                [2 ]Department of Veterinary Microbiology, Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri 600230, Nigeria
                [3 ]Moredun Scientific, Pentlands Science Park, Edinburgh EH26 0PZ, UK; o.ndumnego@ 123456moredun-scientific.com
                [4 ]Design Biologixcc, Building 43b CSIR, Brummeria 0184, South Africa; charlotte@ 123456designbio.co.za (C.E.); angela@ 123456designbio.co.za (A.B.)
                [5 ]Department of Livestock Infectiology and Environmental Hygiene, Institute of Animal Science, University of Hohenheim, 70599 Stuttgart, Germany; wolfgang.beyer@ 123456uni-hohenheim.de
                Author notes
                [* ]Correspondence: sjauro@ 123456unimaid.edu.ng
                Author information
                https://orcid.org/0000-0003-2958-7151
                https://orcid.org/0000-0002-6376-4230
                https://orcid.org/0000-0002-3577-1273
                Article
                vaccines-08-00595
                10.3390/vaccines8040595
                7711464
                33050254
                93d220f4-3143-425e-9651-12dad7701ce4
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 September 2020
                : 01 October 2020
                Categories
                Article

                anthrax,animal vaccination,non-living vaccine
                anthrax, animal vaccination, non-living vaccine

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