Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H7

ABSTRACT Here we exploit the natural properties of a synthetic nanoparticle (NP) scaffold as a subunit vaccine against enterohemorrhagic Escherichia coli (EHEC). Two EHEC-specific immunogenic antigens, namely, LomW and EscC, either alone or in combination, were covalently linked on the surface of go...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Javier I. Sanchez-Villamil, Daniel Tapia, Alfredo G. Torres
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Escherichia coli O157:H7 diarrhea nanovaccines pathogenic Escherichia vaccines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e5b8d9c55e6843ec8963db0b9f1b865e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e5b8d9c55e6843ec8963db0b9f1b865e
record_format	dspace
spelling	oai:doaj.org-article:e5b8d9c55e6843ec8963db0b9f1b865e2021-11-15T16:22:09ZDevelopment of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H710.1128/mBio.01869-192150-7511https://doaj.org/article/e5b8d9c55e6843ec8963db0b9f1b865e2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01869-19https://doaj.org/toc/2150-7511ABSTRACT Here we exploit the natural properties of a synthetic nanoparticle (NP) scaffold as a subunit vaccine against enterohemorrhagic Escherichia coli (EHEC). Two EHEC-specific immunogenic antigens, namely, LomW and EscC, either alone or in combination, were covalently linked on the surface of gold nanoparticles (AuNPs) and used to immunize mice prior to challenge with EHEC O157:H7 strain 86-24. LomW is a putative outer membrane protein encoded in bacteriophage BP-933W, while EscC is a structural type III secretion system protein which forms a ring in the outer membrane. The resulting AuNP preparations, AuNP-LomW and AuNP-EscC, showed that the nanoparticles were able to incorporate the antigens, forming stable formulations that retained robust immunogenicity in vivo after subcutaneous immunization. When administered subcutaneously, AuNP-LomW or AuNP-EscC or a combination containing equivalent amounts of both candidates resulted in higher IgG titers in serum and secretory IgA titers in feces. The serum IgG titers correlated with a significant reduction in EHEC intestinal colonization after 3 days postinoculation. In addition, we showed that serum from antigen-coated AuNP-immunized mice resulted in a reduction of adherence to human intestinal epithelial cells for EHEC, as well as for two other E. coli pathotypes (enteropathogenic E. coli [EPEC], encoding EscC, and enteroaggregative E. coli [EAEC], encoding LomW). Further, the serum had antigen-specific bactericidal properties, engaging the classical complement pathway. Overall, our results demonstrate the immunogenicity and stability of a novel nanovaccine against EHEC. These results also strengthen the prospect of development of a synthetic nanoparticle vaccine conjugated to E. coli antigens as a promising platform against other enteric pathogens. IMPORTANCE Enterohemorrhagic E. coli O157:H7 is a human pathogen and the causative agent of diarrhea and hemorrhagic colitis, which can progress to hemolytic uremic syndrome. These complications represent a serious global public health problem that requires laborious public health interventions and safety control measures to combat recurrent outbreaks worldwide. Today, there are no effective interventions for the control of EHEC infections, and, in fact, the use of antibiotics is counterindicated for EHEC disease. Therefore, a viable alternative for the prevention of human infections is the development of vaccines; however, no such vaccines are approved for human use. In this study, we developed a novel gold nanoparticle platform which acts as a scaffold for the delivery of various antigens, representing a nanovaccine technology which can be applied to several disease models.Javier I. Sanchez-VillamilDaniel TapiaAlfredo G. TorresAmerican Society for MicrobiologyarticleEscherichia coliO157:H7diarrheananovaccinespathogenic EscherichiavaccinesMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Escherichia coli O157:H7 diarrhea nanovaccines pathogenic Escherichia vaccines Microbiology QR1-502
spellingShingle	Escherichia coli O157:H7 diarrhea nanovaccines pathogenic Escherichia vaccines Microbiology QR1-502 Javier I. Sanchez-Villamil Daniel Tapia Alfredo G. Torres Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H7
description	ABSTRACT Here we exploit the natural properties of a synthetic nanoparticle (NP) scaffold as a subunit vaccine against enterohemorrhagic Escherichia coli (EHEC). Two EHEC-specific immunogenic antigens, namely, LomW and EscC, either alone or in combination, were covalently linked on the surface of gold nanoparticles (AuNPs) and used to immunize mice prior to challenge with EHEC O157:H7 strain 86-24. LomW is a putative outer membrane protein encoded in bacteriophage BP-933W, while EscC is a structural type III secretion system protein which forms a ring in the outer membrane. The resulting AuNP preparations, AuNP-LomW and AuNP-EscC, showed that the nanoparticles were able to incorporate the antigens, forming stable formulations that retained robust immunogenicity in vivo after subcutaneous immunization. When administered subcutaneously, AuNP-LomW or AuNP-EscC or a combination containing equivalent amounts of both candidates resulted in higher IgG titers in serum and secretory IgA titers in feces. The serum IgG titers correlated with a significant reduction in EHEC intestinal colonization after 3 days postinoculation. In addition, we showed that serum from antigen-coated AuNP-immunized mice resulted in a reduction of adherence to human intestinal epithelial cells for EHEC, as well as for two other E. coli pathotypes (enteropathogenic E. coli [EPEC], encoding EscC, and enteroaggregative E. coli [EAEC], encoding LomW). Further, the serum had antigen-specific bactericidal properties, engaging the classical complement pathway. Overall, our results demonstrate the immunogenicity and stability of a novel nanovaccine against EHEC. These results also strengthen the prospect of development of a synthetic nanoparticle vaccine conjugated to E. coli antigens as a promising platform against other enteric pathogens. IMPORTANCE Enterohemorrhagic E. coli O157:H7 is a human pathogen and the causative agent of diarrhea and hemorrhagic colitis, which can progress to hemolytic uremic syndrome. These complications represent a serious global public health problem that requires laborious public health interventions and safety control measures to combat recurrent outbreaks worldwide. Today, there are no effective interventions for the control of EHEC infections, and, in fact, the use of antibiotics is counterindicated for EHEC disease. Therefore, a viable alternative for the prevention of human infections is the development of vaccines; however, no such vaccines are approved for human use. In this study, we developed a novel gold nanoparticle platform which acts as a scaffold for the delivery of various antigens, representing a nanovaccine technology which can be applied to several disease models.
format	article
author	Javier I. Sanchez-Villamil Daniel Tapia Alfredo G. Torres
author_facet	Javier I. Sanchez-Villamil Daniel Tapia Alfredo G. Torres
author_sort	Javier I. Sanchez-Villamil
title	Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H7
title_short	Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H7
title_full	Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H7
title_fullStr	Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H7
title_full_unstemmed	Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H7
title_sort	development of a gold nanoparticle vaccine against enterohemorrhagic <named-content content-type="genus-species">escherichia coli</named-content> o157:h7
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e5b8d9c55e6843ec8963db0b9f1b865e
work_keys_str_mv	AT javierisanchezvillamil developmentofagoldnanoparticlevaccineagainstenterohemorrhagicnamedcontentcontenttypegenusspeciesescherichiacolinamedcontento157h7 AT danieltapia developmentofagoldnanoparticlevaccineagainstenterohemorrhagicnamedcontentcontenttypegenusspeciesescherichiacolinamedcontento157h7 AT alfredogtorres developmentofagoldnanoparticlevaccineagainstenterohemorrhagicnamedcontentcontenttypegenusspeciesescherichiacolinamedcontento157h7
_version_	1718426939414282240

Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> O157:H7

Ejemplares similares