
Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection
- Author
- Hans Van Der Weken (UGent) , Hamid Reza Jahantigh, Eric Cox (UGent) and Bert Devriendt (UGent)
- Organization
- Abstract
- Oral subunit vaccines are an interesting alternative strategy to traditional live-attenuated or inactivated vaccines for conferring protection against gut pathogens. Despite being safer and more cost-effective, the development of oral subunit vaccines remains challenging due to barriers imposed by the gastrointestinal tract, such as digestive enzymes, a tolerogenic immune environment and the inability of larger proteins to cross the epithelial barrier. Recent advances have focused on overcoming these barriers by using potent mucosal adjuvants or pH-responsive delivery vehicles to protect antigens from degradation and promote their release in the intestinal lumen. A promising approach to allow vaccine antigens to pass the epithelial barrier is by their targeting towards aminopeptidase N (APN; CD13), an abundant membrane protein present on small intestinal enterocytes. APN is a peptidase involved in digestion, but also a receptor for several enteric pathogens. In addition, upon antibody-mediated crosslinking, APN facilitated the transport of antibody-antigen fusion constructs across the gut epithelium. This epithelial transport resulted in antigen-specific immune responses. Here, we present evidence that oral administration of APN-specific antibody-antigen fusion constructs comprising the porcine IgA Fc-domain and the FedF tipadhesin of F18-fimbriated E. coli elicited both mucosal and systemic immune responses and provided at least partial protection to piglets against a subsequent challenge infection with an F18-fimbriated STEC strain. Altogether, these findings will contribute to the further development of new oral subunit vaccines and provide a first proof-of-concept for the protective efficacy of APN-targeted vaccine antigens.
- Keywords
- Immunology, Immunology and Allergy, oral vaccination, challenge infection, E, coli, aminopeptidase N, mucosal immunity, recombinant antibody, subunit vaccine, ESCHERICHIA-COLI, EDEMA DISEASE, M CELLS, RECEPTOR, IGA, EFFICACY
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01H45GH6C9CZ360VZ6EV252EYY
- MLA
- Van Der Weken, Hans, et al. “Targeted Delivery of Oral Vaccine Antigens to Aminopeptidase N Protects Pigs against Pathogenic E. Coli Challenge Infection.” FRONTIERS IN IMMUNOLOGY, vol. 14, Frontiers Media SA, 2023, doi:10.3389/fimmu.2023.1192715.
- APA
- Van Der Weken, H., Jahantigh, H. R., Cox, E., & Devriendt, B. (2023). Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection. FRONTIERS IN IMMUNOLOGY, 14. https://doi.org/10.3389/fimmu.2023.1192715
- Chicago author-date
- Van Der Weken, Hans, Hamid Reza Jahantigh, Eric Cox, and Bert Devriendt. 2023. “Targeted Delivery of Oral Vaccine Antigens to Aminopeptidase N Protects Pigs against Pathogenic E. Coli Challenge Infection.” FRONTIERS IN IMMUNOLOGY 14. https://doi.org/10.3389/fimmu.2023.1192715.
- Chicago author-date (all authors)
- Van Der Weken, Hans, Hamid Reza Jahantigh, Eric Cox, and Bert Devriendt. 2023. “Targeted Delivery of Oral Vaccine Antigens to Aminopeptidase N Protects Pigs against Pathogenic E. Coli Challenge Infection.” FRONTIERS IN IMMUNOLOGY 14. doi:10.3389/fimmu.2023.1192715.
- Vancouver
- 1.Van Der Weken H, Jahantigh HR, Cox E, Devriendt B. Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection. FRONTIERS IN IMMUNOLOGY. 2023;14.
- IEEE
- [1]H. Van Der Weken, H. R. Jahantigh, E. Cox, and B. Devriendt, “Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection,” FRONTIERS IN IMMUNOLOGY, vol. 14, 2023.
@article{01H45GH6C9CZ360VZ6EV252EYY, abstract = {{Oral subunit vaccines are an interesting alternative strategy to traditional live-attenuated or inactivated vaccines for conferring protection against gut pathogens. Despite being safer and more cost-effective, the development of oral subunit vaccines remains challenging due to barriers imposed by the gastrointestinal tract, such as digestive enzymes, a tolerogenic immune environment and the inability of larger proteins to cross the epithelial barrier. Recent advances have focused on overcoming these barriers by using potent mucosal adjuvants or pH-responsive delivery vehicles to protect antigens from degradation and promote their release in the intestinal lumen. A promising approach to allow vaccine antigens to pass the epithelial barrier is by their targeting towards aminopeptidase N (APN; CD13), an abundant membrane protein present on small intestinal enterocytes. APN is a peptidase involved in digestion, but also a receptor for several enteric pathogens. In addition, upon antibody-mediated crosslinking, APN facilitated the transport of antibody-antigen fusion constructs across the gut epithelium. This epithelial transport resulted in antigen-specific immune responses. Here, we present evidence that oral administration of APN-specific antibody-antigen fusion constructs comprising the porcine IgA Fc-domain and the FedF tipadhesin of F18-fimbriated E. coli elicited both mucosal and systemic immune responses and provided at least partial protection to piglets against a subsequent challenge infection with an F18-fimbriated STEC strain. Altogether, these findings will contribute to the further development of new oral subunit vaccines and provide a first proof-of-concept for the protective efficacy of APN-targeted vaccine antigens.}}, author = {{Van Der Weken, Hans and Jahantigh, Hamid Reza and Cox, Eric and Devriendt, Bert}}, issn = {{1664-3224}}, journal = {{FRONTIERS IN IMMUNOLOGY}}, keywords = {{Immunology,Immunology and Allergy,oral vaccination,challenge infection,E,coli,aminopeptidase N,mucosal immunity,recombinant antibody,subunit vaccine,ESCHERICHIA-COLI,EDEMA DISEASE,M CELLS,RECEPTOR,IGA,EFFICACY}}, language = {{eng}}, pages = {{8}}, publisher = {{Frontiers Media SA}}, title = {{Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection}}, url = {{http://doi.org/10.3389/fimmu.2023.1192715}}, volume = {{14}}, year = {{2023}}, }
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