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dc.contributor.author
Verma, Richa
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Sahu, Rajnish
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Dixit, Saurabh
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Duncan, Skyla A.
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Giambartolomei, Guillermo Hernan
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Singh, Shree R.
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Dennis, Vida A.
dc.date.available
2020-03-13T13:17:47Z
dc.date.issued
2018-10
dc.identifier.citation
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
dc.identifier.issn
1664-3224
dc.identifier.uri
http://hdl.handle.net/11336/99436
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media S.A.
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CHLAMYDIA
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IFN-Γ
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MUCOSAL IGA
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NANOVACCINE
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NEUTRALIZING ANTIBODIES
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PLA-PEG NANOPARTICLES
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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dc.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
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-16T20:59:02Z
dc.journal.volume
9
dc.journal.number
OCT
dc.journal.pagination
1-16
dc.journal.pais
Suiza
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Fil: Verma, Richa. Alabama State University; Estados Unidos
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Fil: Sahu, Rajnish. Alabama State University; Estados Unidos
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Fil: Dixit, Saurabh. Alabama State University; Estados Unidos
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Fil: Duncan, Skyla A.. Alabama State University; Estados Unidos
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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
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Fil: Singh, Shree R.. Alabama State University; Estados Unidos
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Fil: Dennis, Vida A.. Alabama State University; Estados Unidos
dc.journal.title
Frontiers in Immunology
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info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2018.02369/full
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info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fimmu.2018.02369
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