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Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection

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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

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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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