The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a...

Autores
Verma, Richa; Sahu, Rajnish; Dixit, Saurabh; Duncan, Skyla A.; Giambartolomei, Guillermo Hernan; Singh, Shree R.; Dennis, Vida A.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Recently, we reported that our PPM chlamydial nanovaccine [a biodegradable co-polymeric PLA-PEG (poly(lactic acid)-poly(ethylene glycol))-encapsulated M278 peptide (derived from the major outer membrane protein (MOMP) of Chlamydia)] exploits the caveolin-mediated endocytosis pathway for endosomal processing and MHC class II presentation to immune-potentiate Chlamydia-specific CD4+ T-cell immune effector responses. In the present study, we employed the Chlamydia muridarum mouse infection model to evaluate the protective efficacy of PPM against a genital tract challenge. Our results show that mice immunized with PPM were significantly protected against a homologous genital tract challenge evidently by reduced vaginal bacterial loads. Protection of mice correlated with enhanced Chlamydia-specific adaptive immune responses predominated by IFN-γ along with CD4+ T-cells proliferation and their differentiation to CD4+ memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) T-cell phenotypes. We observed the elevation of M278- and MOMP-specific serum antibodies with high avidity in the ascending order IgG1 > IgG2b > IgG2a. A key finding was the elevated mucosal IgG1 and IgA antibody titers followed by an increase in MOMP-specific IgA after the challenge. The Th1/Th2 antibody titer ratios (IgG2a/IgG1 and IgG2b/IgG1) revealed that PPM evoked a Th2-directed response, which skewed to a Th1-dominated antibody response after the bacterial challenge of mice. In addition, PPM immune sera neutralized the infectivity of C. muridarum in McCoy cells, suggesting the triggering of functional neutralizing antibodies. Herein, we reveal for the first time that subcutaneous immunization with the self-adjuvanting biodegradable co-polymeric PPM nanovaccine immune-potentiated robust CD4+ T cell-mediated immune effector responses; a mixed Th1 and Th2 antibody response and local mucosal IgA to protect mice against a chlamydial genital tract challenge.
Fil: Verma, Richa. Alabama State University; Estados Unidos
Fil: Sahu, Rajnish. Alabama State University; Estados Unidos
Fil: Dixit, Saurabh. Alabama State University; Estados Unidos
Fil: Duncan, Skyla A.. Alabama State University; Estados Unidos
Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Singh, Shree R.. Alabama State University; Estados Unidos
Fil: Dennis, Vida A.. Alabama State University; Estados Unidos
Materia
CHLAMYDIA
IFN-Γ
MUCOSAL IGA
NANOVACCINE
NEUTRALIZING ANTIBODIES
PLA-PEG NANOPARTICLES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/99436
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/99436
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responsesVerma, RichaSahu, RajnishDixit, SaurabhDuncan, Skyla A.Giambartolomei, Guillermo HernanSingh, Shree R.Dennis, Vida A.CHLAMYDIAIFN-ΓMUCOSAL IGANANOVACCINENEUTRALIZING ANTIBODIESPLA-PEG NANOPARTICLEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Recently, we reported that our PPM chlamydial nanovaccine [a biodegradable co-polymeric PLA-PEG (poly(lactic acid)-poly(ethylene glycol))-encapsulated M278 peptide (derived from the major outer membrane protein (MOMP) of Chlamydia)] exploits the caveolin-mediated endocytosis pathway for endosomal processing and MHC class II presentation to immune-potentiate Chlamydia-specific CD4+ T-cell immune effector responses. In the present study, we employed the Chlamydia muridarum mouse infection model to evaluate the protective efficacy of PPM against a genital tract challenge. Our results show that mice immunized with PPM were significantly protected against a homologous genital tract challenge evidently by reduced vaginal bacterial loads. Protection of mice correlated with enhanced Chlamydia-specific adaptive immune responses predominated by IFN-γ along with CD4+ T-cells proliferation and their differentiation to CD4+ memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) T-cell phenotypes. We observed the elevation of M278- and MOMP-specific serum antibodies with high avidity in the ascending order IgG1 > IgG2b > IgG2a. A key finding was the elevated mucosal IgG1 and IgA antibody titers followed by an increase in MOMP-specific IgA after the challenge. The Th1/Th2 antibody titer ratios (IgG2a/IgG1 and IgG2b/IgG1) revealed that PPM evoked a Th2-directed response, which skewed to a Th1-dominated antibody response after the bacterial challenge of mice. In addition, PPM immune sera neutralized the infectivity of C. muridarum in McCoy cells, suggesting the triggering of functional neutralizing antibodies. Herein, we reveal for the first time that subcutaneous immunization with the self-adjuvanting biodegradable co-polymeric PPM nanovaccine immune-potentiated robust CD4+ T cell-mediated immune effector responses; a mixed Th1 and Th2 antibody response and local mucosal IgA to protect mice against a chlamydial genital tract challenge.Fil: Verma, Richa. Alabama State University; Estados UnidosFil: Sahu, Rajnish. Alabama State University; Estados UnidosFil: Dixit, Saurabh. Alabama State University; Estados UnidosFil: Duncan, Skyla A.. Alabama State University; Estados UnidosFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Singh, Shree R.. Alabama State University; Estados UnidosFil: Dennis, Vida A.. Alabama State University; Estados UnidosFrontiers Media S.A.2018-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/99436Verma, Richa; Sahu, Rajnish; Dixit, Saurabh; Duncan, Skyla A.; Giambartolomei, Guillermo Hernan; et al.; The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses; Frontiers Media S.A.; Frontiers in Immunology; 9; OCT; 10-2018; 1-161664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2018.02369/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02369info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:25:11Zoai:ri.conicet.gov.ar:11336/99436instacron: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 11:25:12.139CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses
title The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses
spellingShingle The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses
Verma, Richa
CHLAMYDIA
IFN-Γ
MUCOSAL IGA
NANOVACCINE
NEUTRALIZING ANTIBODIES
PLA-PEG NANOPARTICLES
title_short The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses
title_full The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses
title_fullStr The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses
title_full_unstemmed The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses
title_sort The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses
dc.creator.none.fl_str_mv Verma, Richa
Sahu, Rajnish
Dixit, Saurabh
Duncan, Skyla A.
Giambartolomei, Guillermo Hernan
Singh, Shree R.
Dennis, Vida A.
author Verma, Richa
author_facet Verma, Richa
Sahu, Rajnish
Dixit, Saurabh
Duncan, Skyla A.
Giambartolomei, Guillermo Hernan
Singh, Shree R.
Dennis, Vida A.
author_role author
author2 Sahu, Rajnish
Dixit, Saurabh
Duncan, Skyla A.
Giambartolomei, Guillermo Hernan
Singh, Shree R.
Dennis, Vida A.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CHLAMYDIA
IFN-Γ
MUCOSAL IGA
NANOVACCINE
NEUTRALIZING ANTIBODIES
PLA-PEG NANOPARTICLES
topic CHLAMYDIA
IFN-Γ
MUCOSAL IGA
NANOVACCINE
NEUTRALIZING ANTIBODIES
PLA-PEG NANOPARTICLES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Recently, we reported that our PPM chlamydial nanovaccine [a biodegradable co-polymeric PLA-PEG (poly(lactic acid)-poly(ethylene glycol))-encapsulated M278 peptide (derived from the major outer membrane protein (MOMP) of Chlamydia)] exploits the caveolin-mediated endocytosis pathway for endosomal processing and MHC class II presentation to immune-potentiate Chlamydia-specific CD4+ T-cell immune effector responses. In the present study, we employed the Chlamydia muridarum mouse infection model to evaluate the protective efficacy of PPM against a genital tract challenge. Our results show that mice immunized with PPM were significantly protected against a homologous genital tract challenge evidently by reduced vaginal bacterial loads. Protection of mice correlated with enhanced Chlamydia-specific adaptive immune responses predominated by IFN-γ along with CD4+ T-cells proliferation and their differentiation to CD4+ memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) T-cell phenotypes. We observed the elevation of M278- and MOMP-specific serum antibodies with high avidity in the ascending order IgG1 > IgG2b > IgG2a. A key finding was the elevated mucosal IgG1 and IgA antibody titers followed by an increase in MOMP-specific IgA after the challenge. The Th1/Th2 antibody titer ratios (IgG2a/IgG1 and IgG2b/IgG1) revealed that PPM evoked a Th2-directed response, which skewed to a Th1-dominated antibody response after the bacterial challenge of mice. In addition, PPM immune sera neutralized the infectivity of C. muridarum in McCoy cells, suggesting the triggering of functional neutralizing antibodies. Herein, we reveal for the first time that subcutaneous immunization with the self-adjuvanting biodegradable co-polymeric PPM nanovaccine immune-potentiated robust CD4+ T cell-mediated immune effector responses; a mixed Th1 and Th2 antibody response and local mucosal IgA to protect mice against a chlamydial genital tract challenge.
Fil: Verma, Richa. Alabama State University; Estados Unidos
Fil: Sahu, Rajnish. Alabama State University; Estados Unidos
Fil: Dixit, Saurabh. Alabama State University; Estados Unidos
Fil: Duncan, Skyla A.. Alabama State University; Estados Unidos
Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Singh, Shree R.. Alabama State University; Estados Unidos
Fil: Dennis, Vida A.. Alabama State University; Estados Unidos
description Recently, we reported that our PPM chlamydial nanovaccine [a biodegradable co-polymeric PLA-PEG (poly(lactic acid)-poly(ethylene glycol))-encapsulated M278 peptide (derived from the major outer membrane protein (MOMP) of Chlamydia)] exploits the caveolin-mediated endocytosis pathway for endosomal processing and MHC class II presentation to immune-potentiate Chlamydia-specific CD4+ T-cell immune effector responses. In the present study, we employed the Chlamydia muridarum mouse infection model to evaluate the protective efficacy of PPM against a genital tract challenge. Our results show that mice immunized with PPM were significantly protected against a homologous genital tract challenge evidently by reduced vaginal bacterial loads. Protection of mice correlated with enhanced Chlamydia-specific adaptive immune responses predominated by IFN-γ along with CD4+ T-cells proliferation and their differentiation to CD4+ memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) T-cell phenotypes. We observed the elevation of M278- and MOMP-specific serum antibodies with high avidity in the ascending order IgG1 > IgG2b > IgG2a. A key finding was the elevated mucosal IgG1 and IgA antibody titers followed by an increase in MOMP-specific IgA after the challenge. The Th1/Th2 antibody titer ratios (IgG2a/IgG1 and IgG2b/IgG1) revealed that PPM evoked a Th2-directed response, which skewed to a Th1-dominated antibody response after the bacterial challenge of mice. In addition, PPM immune sera neutralized the infectivity of C. muridarum in McCoy cells, suggesting the triggering of functional neutralizing antibodies. Herein, we reveal for the first time that subcutaneous immunization with the self-adjuvanting biodegradable co-polymeric PPM nanovaccine immune-potentiated robust CD4+ T cell-mediated immune effector responses; a mixed Th1 and Th2 antibody response and local mucosal IgA to protect mice against a chlamydial genital tract challenge.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
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/11336/99436
Verma, Richa; Sahu, Rajnish; Dixit, Saurabh; Duncan, Skyla A.; Giambartolomei, Guillermo Hernan; et al.; The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses; Frontiers Media S.A.; Frontiers in Immunology; 9; OCT; 10-2018; 1-16
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/99436
identifier_str_mv Verma, Richa; Sahu, Rajnish; Dixit, Saurabh; Duncan, Skyla A.; Giambartolomei, Guillermo Hernan; et al.; The Chlamydia M278 Major outer membrane peptide encapsulated in the poly(lactic acid)-poly(ethylene glycol) nanoparticulate self-adjuvanting delivery system protects mice against a Chlamydia muridarumgenital tract challenge by stimulating robust systemic and local mucosal immune responses; Frontiers Media S.A.; Frontiers in Immunology; 9; OCT; 10-2018; 1-16
1664-3224
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/fimmu.2018.02369/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02369
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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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