An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses

Autores
Müller, Melisa Florencia; Sacur, Jacinto Alfredo; Matias Brancher, Julia Rafaela; Vera, María Daniela; Arce, Lorena Paola; Raya Tonetti, María Fernanda; Kitazawa, Haruki; Villena, Julio Cesar; Vizoso Pinto, María Guadalupe
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction: The development of a hepatitis E virus (HEV) vaccine is critical, with ORF2 capsid protein as the main target. We previously demonstrated that oral coadministration of recombinant ORF2 with immunomodulatory bacterium-like-particles (IBLP) induces a specific immune response in mice, particularly using IBLP derived from Lacticaseibacillus rhamnosus IBL027 (IBLP027), which was effective in eliciting a local humoral response. IBLP are non-live bacteria with adjuvant and carrier properties, serving as a platform for exposing proteins or antigens fused to LysM (lysine motif) domains, protein modules that bind to cell wall polysaccharides like peptidoglycan.Materials: We cloned the most immunogenic domain of ORF2 (O2P2) fused to five LysM domains (LysM5O2P2) and displayed this chimeric protein on the surface of IBLP027 to create a prototype vaccine (IBLP027-LysM5O2P2). We evaluated its capacity to induce an immune response in vivo by immunizing mice with three doses of either the experimental vaccine or the chimeric protein alone, using an oral or a combined schedule with subcutaneous priming followed by oral boosting. Control groups received IBLP027. Sera and small intestine fluid were analyzed for humoral response, while Peyer’s patches and spleen immune cells were used for ex vivo stimulation with capsid protein to assess cellular response.Results: The oral scheme failed to elicit an IgG response, but this was overcome by a subcutaneous priming dose followed by oral boosters, which led to increasing IgG titers in the combined scheme. The highest IgG titers were seen in the vaccine prototype group. Most groups produced significantly higher IgA levels in intestinal fluid, especially in those that received the oral scheme. Cellular response studies showed increased tumor necrosis factor (TNF)-α, interferon (IFN)-γ interleukin (IL)-4, and IL-17 levels in groups receiving the chimeric protein via oral or combined schedules.Conclusion: Further and continuous research is needed to better understand both the needs and expectations of students and supervisors in different academic realities, including in Veterinary Medicine schools, from which the information available on the subject is scarce.
Fil: Müller, Melisa Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Sacur, Jacinto Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Matias Brancher, Julia Rafaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Vera, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Arce, Lorena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Raya Tonetti, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
Fil: Kitazawa, Haruki. Tohoku University; Japón
Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
Fil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Materia
hepatitis
antigen-display
lactic acid bacteria
recombinant antigen
ORF2
immunomodulatory bacterium-like-particles
antigen-display
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/263431
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/263431
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responsesMüller, Melisa FlorenciaSacur, Jacinto AlfredoMatias Brancher, Julia RafaelaVera, María DanielaArce, Lorena PaolaRaya Tonetti, María FernandaKitazawa, HarukiVillena, Julio CesarVizoso Pinto, María Guadalupehepatitisantigen-displaylactic acid bacteriarecombinant antigenORF2immunomodulatory bacterium-like-particlesantigen-displayhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Introduction: The development of a hepatitis E virus (HEV) vaccine is critical, with ORF2 capsid protein as the main target. We previously demonstrated that oral coadministration of recombinant ORF2 with immunomodulatory bacterium-like-particles (IBLP) induces a specific immune response in mice, particularly using IBLP derived from Lacticaseibacillus rhamnosus IBL027 (IBLP027), which was effective in eliciting a local humoral response. IBLP are non-live bacteria with adjuvant and carrier properties, serving as a platform for exposing proteins or antigens fused to LysM (lysine motif) domains, protein modules that bind to cell wall polysaccharides like peptidoglycan.Materials: We cloned the most immunogenic domain of ORF2 (O2P2) fused to five LysM domains (LysM5O2P2) and displayed this chimeric protein on the surface of IBLP027 to create a prototype vaccine (IBLP027-LysM5O2P2). We evaluated its capacity to induce an immune response in vivo by immunizing mice with three doses of either the experimental vaccine or the chimeric protein alone, using an oral or a combined schedule with subcutaneous priming followed by oral boosting. Control groups received IBLP027. Sera and small intestine fluid were analyzed for humoral response, while Peyer’s patches and spleen immune cells were used for ex vivo stimulation with capsid protein to assess cellular response.Results: The oral scheme failed to elicit an IgG response, but this was overcome by a subcutaneous priming dose followed by oral boosters, which led to increasing IgG titers in the combined scheme. The highest IgG titers were seen in the vaccine prototype group. Most groups produced significantly higher IgA levels in intestinal fluid, especially in those that received the oral scheme. Cellular response studies showed increased tumor necrosis factor (TNF)-α, interferon (IFN)-γ interleukin (IL)-4, and IL-17 levels in groups receiving the chimeric protein via oral or combined schedules.Conclusion: Further and continuous research is needed to better understand both the needs and expectations of students and supervisors in different academic realities, including in Veterinary Medicine schools, from which the information available on the subject is scarce.Fil: Müller, Melisa Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Sacur, Jacinto Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Matias Brancher, Julia Rafaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Vera, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Arce, Lorena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Raya Tonetti, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFrontiers Media2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/263431Müller, Melisa Florencia; Sacur, Jacinto Alfredo; Matias Brancher, Julia Rafaela; Vera, María Daniela; Arce, Lorena Paola; et al.; An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses; Frontiers Media; Frontiers in Microbiology; 15; 12-2024; 1-111664-302XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2024.1512018/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2024.1512018info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:03:57Zoai:ri.conicet.gov.ar:11336/263431instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:03:57.693CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses
title An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses
spellingShingle An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses
Müller, Melisa Florencia
hepatitis
antigen-display
lactic acid bacteria
recombinant antigen
ORF2
immunomodulatory bacterium-like-particles
antigen-display
title_short An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses
title_full An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses
title_fullStr An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses
title_full_unstemmed An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses
title_sort An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses
dc.creator.none.fl_str_mv Müller, Melisa Florencia
Sacur, Jacinto Alfredo
Matias Brancher, Julia Rafaela
Vera, María Daniela
Arce, Lorena Paola
Raya Tonetti, María Fernanda
Kitazawa, Haruki
Villena, Julio Cesar
Vizoso Pinto, María Guadalupe
author Müller, Melisa Florencia
author_facet Müller, Melisa Florencia
Sacur, Jacinto Alfredo
Matias Brancher, Julia Rafaela
Vera, María Daniela
Arce, Lorena Paola
Raya Tonetti, María Fernanda
Kitazawa, Haruki
Villena, Julio Cesar
Vizoso Pinto, María Guadalupe
author_role author
author2 Sacur, Jacinto Alfredo
Matias Brancher, Julia Rafaela
Vera, María Daniela
Arce, Lorena Paola
Raya Tonetti, María Fernanda
Kitazawa, Haruki
Villena, Julio Cesar
Vizoso Pinto, María Guadalupe
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv hepatitis
antigen-display
lactic acid bacteria
recombinant antigen
ORF2
immunomodulatory bacterium-like-particles
antigen-display
topic hepatitis
antigen-display
lactic acid bacteria
recombinant antigen
ORF2
immunomodulatory bacterium-like-particles
antigen-display
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Introduction: The development of a hepatitis E virus (HEV) vaccine is critical, with ORF2 capsid protein as the main target. We previously demonstrated that oral coadministration of recombinant ORF2 with immunomodulatory bacterium-like-particles (IBLP) induces a specific immune response in mice, particularly using IBLP derived from Lacticaseibacillus rhamnosus IBL027 (IBLP027), which was effective in eliciting a local humoral response. IBLP are non-live bacteria with adjuvant and carrier properties, serving as a platform for exposing proteins or antigens fused to LysM (lysine motif) domains, protein modules that bind to cell wall polysaccharides like peptidoglycan.Materials: We cloned the most immunogenic domain of ORF2 (O2P2) fused to five LysM domains (LysM5O2P2) and displayed this chimeric protein on the surface of IBLP027 to create a prototype vaccine (IBLP027-LysM5O2P2). We evaluated its capacity to induce an immune response in vivo by immunizing mice with three doses of either the experimental vaccine or the chimeric protein alone, using an oral or a combined schedule with subcutaneous priming followed by oral boosting. Control groups received IBLP027. Sera and small intestine fluid were analyzed for humoral response, while Peyer’s patches and spleen immune cells were used for ex vivo stimulation with capsid protein to assess cellular response.Results: The oral scheme failed to elicit an IgG response, but this was overcome by a subcutaneous priming dose followed by oral boosters, which led to increasing IgG titers in the combined scheme. The highest IgG titers were seen in the vaccine prototype group. Most groups produced significantly higher IgA levels in intestinal fluid, especially in those that received the oral scheme. Cellular response studies showed increased tumor necrosis factor (TNF)-α, interferon (IFN)-γ interleukin (IL)-4, and IL-17 levels in groups receiving the chimeric protein via oral or combined schedules.Conclusion: Further and continuous research is needed to better understand both the needs and expectations of students and supervisors in different academic realities, including in Veterinary Medicine schools, from which the information available on the subject is scarce.
Fil: Müller, Melisa Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Sacur, Jacinto Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Matias Brancher, Julia Rafaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Vera, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Arce, Lorena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Raya Tonetti, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
Fil: Kitazawa, Haruki. Tohoku University; Japón
Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
Fil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
description Introduction: The development of a hepatitis E virus (HEV) vaccine is critical, with ORF2 capsid protein as the main target. We previously demonstrated that oral coadministration of recombinant ORF2 with immunomodulatory bacterium-like-particles (IBLP) induces a specific immune response in mice, particularly using IBLP derived from Lacticaseibacillus rhamnosus IBL027 (IBLP027), which was effective in eliciting a local humoral response. IBLP are non-live bacteria with adjuvant and carrier properties, serving as a platform for exposing proteins or antigens fused to LysM (lysine motif) domains, protein modules that bind to cell wall polysaccharides like peptidoglycan.Materials: We cloned the most immunogenic domain of ORF2 (O2P2) fused to five LysM domains (LysM5O2P2) and displayed this chimeric protein on the surface of IBLP027 to create a prototype vaccine (IBLP027-LysM5O2P2). We evaluated its capacity to induce an immune response in vivo by immunizing mice with three doses of either the experimental vaccine or the chimeric protein alone, using an oral or a combined schedule with subcutaneous priming followed by oral boosting. Control groups received IBLP027. Sera and small intestine fluid were analyzed for humoral response, while Peyer’s patches and spleen immune cells were used for ex vivo stimulation with capsid protein to assess cellular response.Results: The oral scheme failed to elicit an IgG response, but this was overcome by a subcutaneous priming dose followed by oral boosters, which led to increasing IgG titers in the combined scheme. The highest IgG titers were seen in the vaccine prototype group. Most groups produced significantly higher IgA levels in intestinal fluid, especially in those that received the oral scheme. Cellular response studies showed increased tumor necrosis factor (TNF)-α, interferon (IFN)-γ interleukin (IL)-4, and IL-17 levels in groups receiving the chimeric protein via oral or combined schedules.Conclusion: Further and continuous research is needed to better understand both the needs and expectations of students and supervisors in different academic realities, including in Veterinary Medicine schools, from which the information available on the subject is scarce.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/263431
Müller, Melisa Florencia; Sacur, Jacinto Alfredo; Matias Brancher, Julia Rafaela; Vera, María Daniela; Arce, Lorena Paola; et al.; An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses; Frontiers Media; Frontiers in Microbiology; 15; 12-2024; 1-11
1664-302X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/263431
identifier_str_mv Müller, Melisa Florencia; Sacur, Jacinto Alfredo; Matias Brancher, Julia Rafaela; Vera, María Daniela; Arce, Lorena Paola; et al.; An experimental chimeric hepatitis E virus vaccine elicits both local and systemic immune responses; Frontiers Media; Frontiers in Microbiology; 15; 12-2024; 1-11
1664-302X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2024.1512018/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2024.1512018
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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