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Pharmaceutics
Volume 14
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10.3390/pharmaceutics14010123
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Article

Oral Immunogenicity of Enterotoxigenic Escherichia coli Outer Membrane Vesicles Encapsulated into Zein Nanoparticles Coated with a Gantrez® AN–Mannosamine Polymer Conjugate

by
Melibea Berzosa
1,
Alzbeta Nemeskalova
1,2,
Alba Calvo
1,
Gemma Quincoces
3,
María Collantes
3,
Felix Pareja
3,
Carlos Gamazo
1 and
Juan Manuel Irache
4,*
1
Department of Microbiology and Parasitology, Institute of Tropical Health, University of Navarra, 31008 Pamplona, Spain
2
Department of Analytical Chemistry, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic
3
Department of Nuclear Medicine, Clínica Universidad de Navarra, 31008 Pamplona, Spain
4
Department of Pharmacy and Pharmaceutical Technology, University of Navarra, 31008 Pamplona, Spain
*
Author to whom correspondence should be addressed.
Pharmaceutics 2022, 14(1), 123; https://doi.org/10.3390/pharmaceutics14010123
Submission received: 16 November 2021 / Revised: 7 December 2021 / Accepted: 28 December 2021 / Published: 4 January 2022
(This article belongs to the Special Issue Drug Delivery Systems for Oral Immunotherapy)
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Abstract

Enterotoxigenic Escherichia coli (ETEC) represents a major cause of morbidity and mortality in the human population. In particular, ETEC infections affect children under the age of five from low-middle income countries. However, there is no licensed vaccine against this pathogen. ETEC vaccine development is challenging since this pathotype expresses a wide variety of antigenically diverse virulence factors whose genes can be modified due to ETEC genetic plasticity. To overcome this challenge, we propose the use of outer membrane vesicles (OMVs) isolated from two ETEC clinical strains. In these OMVs, proteomic studies revealed the presence of important immunogens, such as heat-labile toxin, colonization factors, adhesins and mucinases. Furthermore, these vesicles proved to be immunogenic after subcutaneous administration in BALB/c mice. Since ETEC is an enteropathogen, it is necessary to induce both systemic and mucosal immunity. For this purpose, the vesicles, free or encapsulated in zein nanoparticles coated with a Gantrez®–mannosamine conjugate, were administered orally. Biodistribution studies showed that the encapsulation of OMVs delayed the transit through the gut. These results were confirmed by in vivo study, in which OMV encapsulation resulted in higher levels of specific antibodies IgG2a. Further studies are needed to evaluate the protection efficacy of this vaccine approach.
Keywords: Enterotoxigenic Escherichia coli (ETEC); outer membrane vesicle (OMV); nanoparticles; oral vaccine; Gantrez; mannosamine Enterotoxigenic Escherichia coli (ETEC); outer membrane vesicle (OMV); nanoparticles; oral vaccine; Gantrez; mannosamine

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MDPI and ACS Style

Berzosa, M.; Nemeskalova, A.; Calvo, A.; Quincoces, G.; Collantes, M.; Pareja, F.; Gamazo, C.; Irache, J.M. Oral Immunogenicity of Enterotoxigenic Escherichia coli Outer Membrane Vesicles Encapsulated into Zein Nanoparticles Coated with a Gantrez® AN–Mannosamine Polymer Conjugate. Pharmaceutics 2022, 14, 123. https://doi.org/10.3390/pharmaceutics14010123

AMA Style

Berzosa M, Nemeskalova A, Calvo A, Quincoces G, Collantes M, Pareja F, Gamazo C, Irache JM. Oral Immunogenicity of Enterotoxigenic Escherichia coli Outer Membrane Vesicles Encapsulated into Zein Nanoparticles Coated with a Gantrez® AN–Mannosamine Polymer Conjugate. Pharmaceutics. 2022; 14(1):123. https://doi.org/10.3390/pharmaceutics14010123

Chicago/Turabian Style

Berzosa, Melibea, Alzbeta Nemeskalova, Alba Calvo, Gemma Quincoces, María Collantes, Felix Pareja, Carlos Gamazo, and Juan Manuel Irache. 2022. "Oral Immunogenicity of Enterotoxigenic Escherichia coli Outer Membrane Vesicles Encapsulated into Zein Nanoparticles Coated with a Gantrez® AN–Mannosamine Polymer Conjugate" Pharmaceutics 14, no. 1: 123. https://doi.org/10.3390/pharmaceutics14010123

APA Style

Berzosa, M., Nemeskalova, A., Calvo, A., Quincoces, G., Collantes, M., Pareja, F., Gamazo, C., & Irache, J. M. (2022). Oral Immunogenicity of Enterotoxigenic Escherichia coli Outer Membrane Vesicles Encapsulated into Zein Nanoparticles Coated with a Gantrez® AN–Mannosamine Polymer Conjugate. Pharmaceutics, 14(1), 123. https://doi.org/10.3390/pharmaceutics14010123

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