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.
机构:
Anim Hlth Res Inst, Fayoum Branch, Reference Lab Vet Qual Control Poultry Prod, Al Fayyum 63511, EgyptAnim Hlth Res Inst, Fayoum Branch, Reference Lab Vet Qual Control Poultry Prod, Al Fayyum 63511, Egypt
Abd El-Mawgoud, Ahmed I.
El-Nahass, El-Shayma
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Beni Suef Univ, Dept Pathol, Fac Vet Med, Bani Suwayf 62511, EgyptAnim Hlth Res Inst, Fayoum Branch, Reference Lab Vet Qual Control Poultry Prod, Al Fayyum 63511, Egypt
El-Nahass, El-Shayma
Shany, Salama A. S.
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Beni Suef Univ, Poultry Dis Dept, Fac Vet Med, Bani Suwayf 62511, EgyptAnim Hlth Res Inst, Fayoum Branch, Reference Lab Vet Qual Control Poultry Prod, Al Fayyum 63511, Egypt
Shany, Salama A. S.
EL-Sawah, Azza A.
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Beni Suef Univ, Poultry Dis Dept, Fac Vet Med, Bani Suwayf 62511, EgyptAnim Hlth Res Inst, Fayoum Branch, Reference Lab Vet Qual Control Poultry Prod, Al Fayyum 63511, Egypt
EL-Sawah, Azza A.
Dahshan, Al-Hussien M.
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Beni Suef Univ, Poultry Dis Dept, Fac Vet Med, Bani Suwayf 62511, EgyptAnim Hlth Res Inst, Fayoum Branch, Reference Lab Vet Qual Control Poultry Prod, Al Fayyum 63511, Egypt
Dahshan, Al-Hussien M.
Nasef, Soad A.
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Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, POB 264, Giza 12618, EgyptAnim Hlth Res Inst, Fayoum Branch, Reference Lab Vet Qual Control Poultry Prod, Al Fayyum 63511, Egypt
机构:
Nippon Inst Biol Sci, Res Dept, Tokyo, Japan
Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo 1088639, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Takeyama, Natsumi
Yuki, Yoshikazu
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Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo 1088639, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Yuki, Yoshikazu
Tokuhara, Daisuke
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Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo 1088639, Japan
Osaka City Univ, Grad Sch Med, Dept Pediat, Osaka, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Tokuhara, Daisuke
Oroku, Kazuki
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Nippon Inst Biol Sci, Res Dept, Tokyo, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Oroku, Kazuki
Mejima, Mio
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Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo 1088639, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Mejima, Mio
Kurokawa, Shiho
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Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo 1088639, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Kurokawa, Shiho
Kuroda, Masaharu
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Natl Agr Res Ctr, Rice Physiol Res Team, Kumamoto, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Kuroda, Masaharu
Kodama, Toshiaki
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Nippon Inst Biol Sci, Res Dept, Tokyo, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Kodama, Toshiaki
Nagai, Shinya
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Nippon Inst Biol Sci, Res Dept, Tokyo, Japan
Nisseiken Co Ltd, Tokyo, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Nagai, Shinya
Ueda, Susumu
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Nippon Inst Biol Sci, Res Dept, Tokyo, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan
Ueda, Susumu
Kiyono, Hiroshi
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Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo 1088639, Japan
Univ Tokyo, Inst Med Sci, Int Res & Dev Ctr Mucosal Vaccine, Tokyo 1088639, JapanNippon Inst Biol Sci, Res Dept, Tokyo, Japan