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.
引用
收藏
页数:8
相关论文
共 50 条
  • [21] Lassa Virus Replicon Particle Vaccine Protects Strain 13/N Guinea Pigs Against Challenge With Geographically and Genetically Diverse Viral Strains
    Spengler, Jessica R.
    Kainulainen, Markus H.
    Welch, Stephen R.
    Coleman-McCray, Jo Ann D.
    Harmon, Jessica R.
    Condrey, Jillian A.
    Scholte, Florine E. M.
    Nichol, Stuart T.
    Montgomery, Joel M.
    Albarino, Cesar G.
    Spiropoulou, Christina F.
    JOURNAL OF INFECTIOUS DISEASES, 2022, 226 (09): : 1545 - 1550
  • [22] Histomorphometric evaluation of intestinal cellular immune responses in pigs immunized with live oral F4ac+ non-enterotoxigenic E. coli vaccine against postweaning colibacillosis
    Janjatovic, A. Kovsca
    Lackovic, G.
    Bozlc, F.
    Kezic, D.
    Popovic, M.
    Valpotic, H.
    Harapin, I.
    Pavicic, Z.
    Njari, B.
    Valpotic, I.
    EUROPEAN JOURNAL OF HISTOCHEMISTRY, 2010, 54 (01): : 18 - 24
  • [23] Histone deacetylase inhibitor therapy boosts RNase 4 and 7 expression and protects against invasive uropathogenic E. coli infection.
    Schwartz, Laura
    Bochter, Skye
    Simoni, Aaron
    Eichler, Tad
    Li, Birong Rollin
    Bender, Kristin
    Santoro, Nicholas
    Linn, Sarah
    Spencer, John David
    PEDIATRIC NEPHROLOGY, 2023, 38 (07) : 2273 - 2273
  • [24] Oral-Delivery Lactococcus lactis expressing cherry fusion lactoferrin peptides against infection of avian pathogenic Escherichia coli in chickens
    Li, Zhuoran
    Wang, Xueying
    Zheng, Dianzhong
    Han, Fuzhen
    Li, Yue
    Zhou, Han
    Li, Jiaxuan
    Cui, Wen
    Jiang, Yanping
    Wang, Xiaona
    Xie, Weichun
    Tang, Lijie
    POULTRY SCIENCE, 2025, 104 (01)
  • [25] Oral delivery of Escherichia coli persistently infected with M2e-displaying bacteriophages partially protects against influenza A virus
    Deng, Lei
    Roose, Kenny
    Job, Emma R.
    De Rycke, Riet
    Van Hamme, Evelien
    Goncalves, Amanda
    Parthoens, Eef
    Cicchelero, Laetitia
    Sanders, Niek
    Fiers, Walter
    Saelens, Xavier
    JOURNAL OF CONTROLLED RELEASE, 2017, 264 : 55 - 65
  • [26] The effects of a novel adjuvant complex/Eimeria profilin vaccine on the intestinal host immune response against live E. acervulina challenge infection
    Lee, Sung-Hyen
    Lillehoj, Hyun S.
    Jang, Seung I.
    Lee, Kyung-Woo
    Yancey, Roberti.
    Dominowski, Paul
    VACCINE, 2010, 28 (39) : 6498 - 6504
  • [27] MV140 Mucosal Vaccine Induces Targeted Immune Response for Enhanced Clearance of Uropathogenic E. coli in Experimental Urinary Tract Infection
    Saz-Leal, Paula
    Ligon, Marianne Morris
    Diez-Rivero, Carmen Maria
    Garcia-Ayuso, Diego
    Mohanty, Soumitra
    Vinuela, Marcos
    Real-Arevalo, Irene
    Conejero, Laura
    Brauner, Annelie
    Subiza, Jose Luis
    Mysorekar, Indira Uppugunduri
    VACCINES, 2024, 12 (05)
  • [28] Bacterial ghost of avian pathogenic E. coli (APEC) serotype O78:K80 as a homologous vaccine against avian colibacillosis
    Ebrahimi-Nik, Hakimeh
    Bassami, Mohammad Reza
    Mohri, Mehrdad
    Rad, Mehrnaz
    Khan, Mazhar I.
    PLOS ONE, 2018, 13 (03):
  • [29] Intranasal delivery of a cDC1 targeted influenza vaccine with poly(I:C) enhances T cell responses and protects against influenza infection
    Lysen, Anna
    Gudjonsson, Arnar
    Tesfaye, Demo Yemane
    Bobic, Sonja
    Bern, Malin
    Bogen, Bjarne
    Fossum, Even
    SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2022, 95 (03)
  • [30] Oral Delivery of a Novel Attenuated Salmonella Vaccine Expressing Influenza A Virus Proteins Protects Mice against H5N1 and H1N1 Viral Infection
    Pei, Zenglin
    Jiang, Xiaohong
    Yang, Zhu
    Ren, Xiaoguang
    Gong, Hao
    Reeves, Michael
    Sheng, Jingxue
    Wang, Yu
    Pan, Zishu
    Liu, Fenyong
    Wu, Jianguo
    Lu, Sangwei
    PLOS ONE, 2015, 10 (06):