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  1. Article ; Online: Generation of a thermostable, oral Zika vaccine that protects against virus challenge in non-human primates.

    Bacon, Andrew / Teixeira, Mauro / Costa, Vivian / Bone, Peter / Simmons, Jennifer / Drew, Jeffrey

    Vaccine

    2023  Volume 41, Issue 15, Page(s) 2524–2533

    Abstract: Here we report the development of a thermally stable, orally administered, candidate Zika vaccine using human serotype 5 adenovirus (AdHu5). We engineered AdHu5 to express the genes for the envelope and NS1 proteins of Zika virus. AdHu5 was formulated ... ...

    Abstract Here we report the development of a thermally stable, orally administered, candidate Zika vaccine using human serotype 5 adenovirus (AdHu5). We engineered AdHu5 to express the genes for the envelope and NS1 proteins of Zika virus. AdHu5 was formulated using a proprietary platform, OraPro, comprising a mix of sugars and modified amino acids that can overcome elevated temperatures (37 C), and an enteric coated capsule that protects the integrity of the AdHu5 from the acid in the stomach. This enables the delivery AdHu5 to the immune system of the small intestine. We show that oral delivery of AdHu5 elicited antigen-specific serum IgG immune responses in a mouse model and in a non-human primate model. Importantly, these immune responses were able reduce viral counts in mice and to prevent detectable viraemia in the non-human primates on challenge with live Zika virus. This candidate vaccine has significant advantages over many current vaccines that are maintained in a cold or ultra-cold chain and require parenteral administration.
    MeSH term(s) Humans ; Animals ; Mice ; Zika Virus ; Vaccines ; Zika Virus Infection ; Primates ; Antigens ; Antibodies, Viral ; Viral Vaccines ; Antibodies, Neutralizing
    Chemical Substances Vaccines ; Antigens ; Antibodies, Viral ; Viral Vaccines ; Antibodies, Neutralizing
    Language English
    Publishing date 2023-03-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2023.02.055
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A reconnaissance survey of farmers' awareness of hypomagnesaemic tetany in UK cattle and sheep farms.

    Kumssa, Diriba B / Penrose, Beth / Bone, Peter A / Lovatt, J Alan / Broadley, Martin R / Kendall, Nigel R / Ander, E Louise

    PloS one

    2019  Volume 14, Issue 10, Page(s) e0223868

    Abstract: Hypomagnesaemic tetany (HypoMgT) in ruminants is a physiological disorder caused by inadequate intake or impaired absorption of magnesium (Mg) in the gut. If it is not detected and treated in time, HypoMgT can cause the death of the affected animal. A ... ...

    Abstract Hypomagnesaemic tetany (HypoMgT) in ruminants is a physiological disorder caused by inadequate intake or impaired absorption of magnesium (Mg) in the gut. If it is not detected and treated in time, HypoMgT can cause the death of the affected animal. A semi-structured questionnaire survey was conducted from July 2016-2017 to assess farmers' awareness of HypoMgT in cattle and sheep in the UK. The questionnaire was distributed to farmers at farm business events and agricultural shows, and through a collaborative group of independent veterinary practices to their clients. Farmers were asked about (i) the incidence of presumed HypoMgT (PHT); (ii) their strategies to treat or prevent HypoMgT; (iii) mineral tests on animals, forage and soil, and (iv) farm enterprise type. A total of 285 responses were received from 82 cattle, 157 mixed cattle and sheep, and 46 sheep farmers, of whom 39% reported HypoMgT in their livestock, affecting 1-30 animals. Treatment and/or prevention against HypoMgT was reported by 96% respondents with PHT and 79% of those without. Mineral tests on animal, forage, and soil was conducted by 24%, 53%, and 66% of the respondents, respectively, regardless of PHT. There was a highly significant association between the use of interventions to tackle HypoMgT and the incidence of PHT (p < 0.01). The top three treatment/prevention strategies used were reported as being free access supplementation (149), in feed supplementation (59) and direct to animal treatments (drenches, boluses and injections) (45) although these did vary by farm type. Although some (9) reported using Mg-lime, no other pasture management interventions were reported (e.g., Mg-fertilisation or sward composition). Generally, the results indicate that UK farmers are aware of the risks of HypoMgT. A more integrated soil-forage-animal assessment may improve the effectiveness of tackling HypoMgT and help highlight the root causes of the problem.
    MeSH term(s) Animals ; Cattle ; Cattle Diseases/epidemiology ; Cattle Diseases/therapy ; Dairying ; Farmers/psychology ; Farms ; Health Knowledge, Attitudes, Practice ; Incidence ; Magnesium Deficiency/complications ; Magnesium Deficiency/epidemiology ; Magnesium Deficiency/therapy ; Magnesium Deficiency/veterinary ; Sheep ; Sheep Diseases/epidemiology ; Sheep Diseases/therapy ; Surveys and Questionnaires ; Tetany/chemically induced ; Tetany/epidemiology ; Tetany/therapy ; Tetany/veterinary ; United Kingdom/epidemiology
    Language English
    Publishing date 2019-10-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0223868
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Establishing the plasma copper reference range in Boer goats.

    McKay, Molly / Bone, Peter / Kendall, Nigel

    The Veterinary record

    2010  Volume 167, Issue 13, Page(s) 499

    MeSH term(s) Animals ; Copper/blood ; Goats/blood ; Reference Values
    Chemical Substances Copper (789U1901C5)
    Language English
    Publishing date 2010-09-25
    Publishing country England
    Document type Letter
    ZDB-ID 390015-0
    ISSN 2042-7670 ; 0042-4900
    ISSN (online) 2042-7670
    ISSN 0042-4900
    DOI 10.1136/vr.c5192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A single locus from the entomopathogenic bacterium Photorhabdus luminescens inhibits activated Manduca sexta phenoloxidase

    Eleftherianos, Ioannis / Waterfield, Nicholas R / Bone, Peter / Boundy, Sam / ffrench-Constant, Richard H / Reynolds, Stuart E

    FEMS microbiology letters. 2009 Apr., v. 293, no. 2

    2009  

    Abstract: Insect blood (hemolymph) contains prophenoloxidase, a proenzyme that is activated to protective phenoloxidase when the insect is damaged or challenged with microorganisms. The Gram-negative bacterium Photorhabdus luminescens kills the lepidopteron insect ...

    Abstract Insect blood (hemolymph) contains prophenoloxidase, a proenzyme that is activated to protective phenoloxidase when the insect is damaged or challenged with microorganisms. The Gram-negative bacterium Photorhabdus luminescens kills the lepidopteron insect Manduca sexta by using a variety of toxins. We screened P. luminescens and Photorhabdus asymbiotica cosmid libraries in an Escherichia coli host against previously activated M. sexta hemolymph phenoloxidase and identified three overlapping cosmid clones from P. luminescens and five from P. asymbiotica that suppressed the activity of the enzyme both in vitro and in vivo. Genome alignments of cosmid end sequences from both species confirmed that they contained orthologous loci. We examined one of the cosmids from P. luminescens in detail: it induced the formation of significantly fewer melanotic nodules, proliferated faster within the insect host and was significantly more virulent towards fifth-stage larvae than E. coli control bacteria. Insertional mutagenesis of this cosmid yielded 11 transposon mutants that were no longer inhibitory. All of these were insertions into a single 5.5-kb locus, which contained three ORFs and was homologous to the maltodextrin phosphorylase locus of E. coli. The implications of this novel inhibitory factor of insect phenoloxidase for Photorhabdus virulence are discussed.
    Keywords Photorhabdus luminescens ; Manduca sexta ; insect immunity
    Language English
    Dates of publication 2009-04
    Size p. 170-176.
    Publisher Blackwell Publishing Ltd
    Publishing place Oxford, UK
    Document type Article
    ZDB-ID 752343-9
    ISSN 1574-6968 ; 0378-1097
    ISSN (online) 1574-6968
    ISSN 0378-1097
    DOI 10.1111/j.1574-6968.2009.01523.x
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: A single locus from the entomopathogenic bacterium Photorhabdus luminescens inhibits activated Manduca sexta phenoloxidase.

    Eleftherianos, Ioannis / Waterfield, Nicholas R / Bone, Peter / Boundy, Sam / ffrench-Constant, Richard H / Reynolds, Stuart E

    FEMS microbiology letters

    2009  Volume 293, Issue 2, Page(s) 170–176

    Abstract: Insect blood (hemolymph) contains prophenoloxidase, a proenzyme that is activated to protective phenoloxidase when the insect is damaged or challenged with microorganisms. The Gram-negative bacterium Photorhabdus luminescens kills the lepidopteron insect ...

    Abstract Insect blood (hemolymph) contains prophenoloxidase, a proenzyme that is activated to protective phenoloxidase when the insect is damaged or challenged with microorganisms. The Gram-negative bacterium Photorhabdus luminescens kills the lepidopteron insect Manduca sexta by using a variety of toxins. We screened P. luminescens and Photorhabdus asymbiotica cosmid libraries in an Escherichia coli host against previously activated M. sexta hemolymph phenoloxidase and identified three overlapping cosmid clones from P. luminescens and five from P. asymbiotica that suppressed the activity of the enzyme both in vitro and in vivo. Genome alignments of cosmid end sequences from both species confirmed that they contained orthologous loci. We examined one of the cosmids from P. luminescens in detail: it induced the formation of significantly fewer melanotic nodules, proliferated faster within the insect host and was significantly more virulent towards fifth-stage larvae than E. coli control bacteria. Insertional mutagenesis of this cosmid yielded 11 transposon mutants that were no longer inhibitory. All of these were insertions into a single 5.5-kb locus, which contained three ORFs and was homologous to the maltodextrin phosphorylase locus of E. coli. The implications of this novel inhibitory factor of insect phenoloxidase for Photorhabdus virulence are discussed.
    MeSH term(s) Animals ; DNA Transposable Elements ; Escherichia coli/genetics ; Gene Knockout Techniques ; Gene Library ; Manduca/enzymology ; Manduca/microbiology ; Monophenol Monooxygenase/antagonists & inhibitors ; Mutagenesis, Insertional ; Photorhabdus/genetics ; Photorhabdus/pathogenicity ; Survival Analysis ; Virulence
    Chemical Substances DNA Transposable Elements ; Monophenol Monooxygenase (EC 1.14.18.1)
    Language English
    Publishing date 2009-02-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 752343-9
    ISSN 1574-6968 ; 0378-1097
    ISSN (online) 1574-6968
    ISSN 0378-1097
    DOI 10.1111/j.1574-6968.2009.01523.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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