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Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica

Bovine respiratory disease (BRD) affects feedlot cattle across North America, resulting in economic losses due to animal treatment and reduced performance. In an effort to develop a vaccine candidate targeting a primary bacterial agent contributing to BRD, we produced a tripartite antigen consisting...

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Autores principales: Kaldis, Angelo, Uddin, Muhammed Salah, Guluarte, Jose Ortiz, Martin, Coby, Alexander, Trevor W., Menassa, Rima
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542578/
https://www.ncbi.nlm.nih.gov/pubmed/37790785
http://dx.doi.org/10.3389/fpls.2023.1251046
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author Kaldis, Angelo
Uddin, Muhammed Salah
Guluarte, Jose Ortiz
Martin, Coby
Alexander, Trevor W.
Menassa, Rima
author_facet Kaldis, Angelo
Uddin, Muhammed Salah
Guluarte, Jose Ortiz
Martin, Coby
Alexander, Trevor W.
Menassa, Rima
author_sort Kaldis, Angelo
collection PubMed
description Bovine respiratory disease (BRD) affects feedlot cattle across North America, resulting in economic losses due to animal treatment and reduced performance. In an effort to develop a vaccine candidate targeting a primary bacterial agent contributing to BRD, we produced a tripartite antigen consisting of segments of the virulence factor Leukotoxin A (LktA) and lipoprotein PlpE from Mannheimia haemolytica, fused to a cholera toxin mucosal adjuvant (CTB). This recombinant subunit vaccine candidate was expressed in the leaves of Nicotiana benthamiana plants, with accumulation tested in five subcellular compartments. The recombinant protein was found to accumulate highest in the endoplasmic reticulum, but targeting to the chloroplast was employed for scaling up production due the absence of post-translational modification while still producing feasible levels. Leaves were freeze dried, then orally administered to mice to determine its immunogenicity. Sera from mice immunized with leaf tissue expressing the recombinant antigen contained IgG antibodies, specifically recognizing both LktA and PlpE. These mice also had a mucosal immune response to the CTB+LktA+PlpE protein as measured by the presence of LktA- and PlpE-specific IgA antibodies in lung and fecal material. Moreover, the antigen remained stable at room temperature with limited deterioration for up to one year when stored as lyophilized plant material. This study demonstrated that a recombinant antigen expressed in plant tissue elicited both humoral and mucosal immune responses when fed to mice, and warrants evaluation in cattle.
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spelling pubmed-105425782023-10-03 Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica Kaldis, Angelo Uddin, Muhammed Salah Guluarte, Jose Ortiz Martin, Coby Alexander, Trevor W. Menassa, Rima Front Plant Sci Plant Science Bovine respiratory disease (BRD) affects feedlot cattle across North America, resulting in economic losses due to animal treatment and reduced performance. In an effort to develop a vaccine candidate targeting a primary bacterial agent contributing to BRD, we produced a tripartite antigen consisting of segments of the virulence factor Leukotoxin A (LktA) and lipoprotein PlpE from Mannheimia haemolytica, fused to a cholera toxin mucosal adjuvant (CTB). This recombinant subunit vaccine candidate was expressed in the leaves of Nicotiana benthamiana plants, with accumulation tested in five subcellular compartments. The recombinant protein was found to accumulate highest in the endoplasmic reticulum, but targeting to the chloroplast was employed for scaling up production due the absence of post-translational modification while still producing feasible levels. Leaves were freeze dried, then orally administered to mice to determine its immunogenicity. Sera from mice immunized with leaf tissue expressing the recombinant antigen contained IgG antibodies, specifically recognizing both LktA and PlpE. These mice also had a mucosal immune response to the CTB+LktA+PlpE protein as measured by the presence of LktA- and PlpE-specific IgA antibodies in lung and fecal material. Moreover, the antigen remained stable at room temperature with limited deterioration for up to one year when stored as lyophilized plant material. This study demonstrated that a recombinant antigen expressed in plant tissue elicited both humoral and mucosal immune responses when fed to mice, and warrants evaluation in cattle. Frontiers Media S.A. 2023-09-15 /pmc/articles/PMC10542578/ /pubmed/37790785 http://dx.doi.org/10.3389/fpls.2023.1251046 Text en Copyright © 2023 His Majesty the King in Right of Canada, as represented by the Minister of Agriculture and Agri-Food Canada for the contribution of Angelo Kaldis, Muhammed Salah Uddin, Jose Ortiz Guluarte, Coby Martin, Trevor W. Alexander, Rima Menassa https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Plant Science
Kaldis, Angelo
Uddin, Muhammed Salah
Guluarte, Jose Ortiz
Martin, Coby
Alexander, Trevor W.
Menassa, Rima
Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica
title Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica
title_full Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica
title_fullStr Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica
title_full_unstemmed Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica
title_short Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica
title_sort development of a plant-based oral vaccine candidate against the bovine respiratory pathogen mannheimia haemolytica
topic Plant Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542578/
https://www.ncbi.nlm.nih.gov/pubmed/37790785
http://dx.doi.org/10.3389/fpls.2023.1251046
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