Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles
Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. The immune protection of the piglets derives from maternal colostrum, since this species does not receive maternal antibodies through the placenta. In the present study, outer...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-12-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/8/1/11 |
| _version_ | 1798041403688747008 |
|---|---|
| author | Jose Matías Ana Brotons Santiago Cenoz Isidoro Pérez Muthanna Abdulkarim Mark Gumbleton Juan M. Irache Carlos Gamazo |
| author_facet | Jose Matías Ana Brotons Santiago Cenoz Isidoro Pérez Muthanna Abdulkarim Mark Gumbleton Juan M. Irache Carlos Gamazo |
| author_sort | Jose Matías |
| collection | DOAJ |
| description | Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. The immune protection of the piglets derives from maternal colostrum, since this species does not receive maternal antibodies through the placenta. In the present study, outer membrane vesicles (OMVs) obtained from main ETEC strains involved in piglet infection (F4 and F18 serotypes), encapsulated into zein nanoparticles coated with Gantrez<sup>®®</sup> AN-mannosamine conjugate, were used to orally immunize mice and pregnant sows. Loaded nanoparticles were homogeneous and spherical in a shape, with a size of 220−280 nm. The diffusion of nanoparticles through porcine intestinal mucus barrier was assessed by a Multiple Particle Tracking technique, showing that these particles were able to diffuse efficiently (1.3% diffusion coefficient), validating their oral use. BALB/c mice were either orally immunized with free OMVs or encapsulated into nanoparticles (100 µg OMVs/mouse). Results indicated that a single dose of loaded nanoparticles was able to elicit higher levels of serum specific IgG1, IgG2a and IgA, as well as intestinal IgA, with respect to the free antigens. In addition, nanoparticles induced an increase in levels of IL-2, IL-4 and IFN-γ with respect to the administration of free OMVs. Orally immunized pregnant sows with the same formulation elicited colostrum-, serum- (IgG, IgA or IgM) and fecal- (IgA) specific antibodies and, what is most relevant, offspring suckling piglets presented specific IgG in serum. Further studies are needed to determine the infection protective capacity of this new oral subunit vaccine |
| first_indexed | 2024-04-11T22:21:03Z |
| format | Article |
| id | doaj.art-8179709746a942a3a4edad72d7cadded |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T22:21:03Z |
| publishDate | 2019-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-8179709746a942a3a4edad72d7cadded2022-12-22T04:00:07ZengMDPI AGVaccines2076-393X2019-12-01811110.3390/vaccines8010011vaccines8010011Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based NanoparticlesJose Matías0Ana Brotons1Santiago Cenoz2Isidoro Pérez3Muthanna Abdulkarim4Mark Gumbleton5Juan M. Irache6Carlos Gamazo7Department of Microbiology and Parasitology, Institute of Tropical Health, University of Navarra, 31008 Pamplona, SpainDepartment of Pharmacy and Pharmaceutical Technology, University of Navarra, 31008 Pamplona, SpainBlue Agro Bioscience, Parque Tecnológico Miramón. Paseo Mikeletegi, 54. 20009 San Sebastián, SpainAgropecuario Obanos, Marcilla, 31340 Navarra, SpainSchool of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF10 3NB, UKSchool of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF10 3NB, UKDepartment of Pharmacy and Pharmaceutical Technology, University of Navarra, 31008 Pamplona, SpainDepartment of Microbiology and Parasitology, Institute of Tropical Health, University of Navarra, 31008 Pamplona, SpainEnterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. The immune protection of the piglets derives from maternal colostrum, since this species does not receive maternal antibodies through the placenta. In the present study, outer membrane vesicles (OMVs) obtained from main ETEC strains involved in piglet infection (F4 and F18 serotypes), encapsulated into zein nanoparticles coated with Gantrez<sup>®®</sup> AN-mannosamine conjugate, were used to orally immunize mice and pregnant sows. Loaded nanoparticles were homogeneous and spherical in a shape, with a size of 220−280 nm. The diffusion of nanoparticles through porcine intestinal mucus barrier was assessed by a Multiple Particle Tracking technique, showing that these particles were able to diffuse efficiently (1.3% diffusion coefficient), validating their oral use. BALB/c mice were either orally immunized with free OMVs or encapsulated into nanoparticles (100 µg OMVs/mouse). Results indicated that a single dose of loaded nanoparticles was able to elicit higher levels of serum specific IgG1, IgG2a and IgA, as well as intestinal IgA, with respect to the free antigens. In addition, nanoparticles induced an increase in levels of IL-2, IL-4 and IFN-γ with respect to the administration of free OMVs. Orally immunized pregnant sows with the same formulation elicited colostrum-, serum- (IgG, IgA or IgM) and fecal- (IgA) specific antibodies and, what is most relevant, offspring suckling piglets presented specific IgG in serum. Further studies are needed to determine the infection protective capacity of this new oral subunit vaccinehttps://www.mdpi.com/2076-393X/8/1/11vaccineouter membrane vesiclesetecescherichia colinanoparticles |
| spellingShingle | Jose Matías Ana Brotons Santiago Cenoz Isidoro Pérez Muthanna Abdulkarim Mark Gumbleton Juan M. Irache Carlos Gamazo Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles Vaccines vaccine outer membrane vesicles etec escherichia coli nanoparticles |
| title | Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles |
| title_full | Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles |
| title_fullStr | Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles |
| title_full_unstemmed | Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles |
| title_short | Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles |
| title_sort | oral immunogenicity in mice and sows of enterotoxigenic escherichia coli outer membrane vesicles incorporated into zein based nanoparticles |
| topic | vaccine outer membrane vesicles etec escherichia coli nanoparticles |
| url | https://www.mdpi.com/2076-393X/8/1/11 |
| work_keys_str_mv | AT josematias oralimmunogenicityinmiceandsowsofenterotoxigenicescherichiacolioutermembranevesiclesincorporatedintozeinbasednanoparticles AT anabrotons oralimmunogenicityinmiceandsowsofenterotoxigenicescherichiacolioutermembranevesiclesincorporatedintozeinbasednanoparticles AT santiagocenoz oralimmunogenicityinmiceandsowsofenterotoxigenicescherichiacolioutermembranevesiclesincorporatedintozeinbasednanoparticles AT isidoroperez oralimmunogenicityinmiceandsowsofenterotoxigenicescherichiacolioutermembranevesiclesincorporatedintozeinbasednanoparticles AT muthannaabdulkarim oralimmunogenicityinmiceandsowsofenterotoxigenicescherichiacolioutermembranevesiclesincorporatedintozeinbasednanoparticles AT markgumbleton oralimmunogenicityinmiceandsowsofenterotoxigenicescherichiacolioutermembranevesiclesincorporatedintozeinbasednanoparticles AT juanmirache oralimmunogenicityinmiceandsowsofenterotoxigenicescherichiacolioutermembranevesiclesincorporatedintozeinbasednanoparticles AT carlosgamazo oralimmunogenicityinmiceandsowsofenterotoxigenicescherichiacolioutermembranevesiclesincorporatedintozeinbasednanoparticles |