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

Frontiers in Plant Science

Plant Science

Jose Ortiz Guluarte¹  Trevor W. Alexander¹  Muhammed Salah Uddin²  Angelo Kaldis³  Coby Martin⁴  Rima Menassa⁴ 

[1] Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB, Canada;Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB, Canada;Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada;London Research and Development Centre, Agriculture and Agri-Food Canada, London, ON, Canada;London Research and Development Centre, Agriculture and Agri-Food Canada, London, ON, Canada;Department of Biology, Western University, London, ON, Canada;

关键词: bovine respiratory disease;    plant-made vaccine;    oral vaccine;    Mannheimia haemolytica;    molecular farming;    mucosal immunity;    agroinfiltration;   

DOI  :  10.3389/fpls.2023.1251046

 received in 2023-06-30, accepted in 2023-08-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
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