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

被引:2
|
作者
van der Weken, Hans [1 ]
Jahantigh, Hamid Reza [2 ,3 ]
Cox, Eric [1 ]
Devriendt, Bert [1 ]
机构
[1] Univ Ghent, Fac Vet Med, Dept Translat Physiol Infectiol & Publ Hlth, Lab Immunol, Merelbeke, Belgium
[2] Emory Univ, Fac Med, Dept Pathol, Atlanta, GA USA
[3] Univ Bari, Interdisciplinary Dept Med, Sect Occupat Med, Bari, Italy
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
关键词
oral vaccination; challenge infection; E; coli; aminopeptidase N; epithelial targeting; mucosal immunity; recombinant antibody; subunit vaccine; ESCHERICHIA-COLI; EDEMA DISEASE; M CELLS; RECEPTOR; IGA; EFFICACY;
D O I
10.3389/fimmu.2023.1192715
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页数:8
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