A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of...

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Autores: Martín De La Cruz, Leticia, Sevilla Ortega, Carmen, Benito Villalvilla, Cristina, Díez Rivero, Carmen, Sánchez Ramón, Silvia María, Subiza Garrido-Lestache, José Luis, Palomares Gracia, Óscar
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/95337
Acceso en línea:https://hdl.handle.net/20.500.14352/95337
Access Level:acceso abierto
Palabra clave:577.1
Dendritic cells
Recurrent urinary tract infections (RUTIs)
Recurrent vulvovaginal candidiasis (RVVCs)
Trained immunity-based vaccines (TIbVs)
Candida albicans V132
Polybacterial preparation MV140
Inmunología
Bioquímica (Química)
Biología molecular (Química)
Bioquímica (Farmacia)
2412 Inmunología
2302 Bioquímica
2403 Bioquímica
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oai_identifier_str oai:docta.ucm.es:20.500.14352/95337
network_acronym_str ES
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repository_id_str
spelling A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract InfectionsMartín De La Cruz, LeticiaSevilla Ortega, CarmenBenito Villalvilla, CristinaDíez Rivero, CarmenSánchez Ramón, Silvia MaríaSubiza Garrido-Lestache, José LuisPalomares Gracia, Óscar577.1Dendritic cellsRecurrent urinary tract infections (RUTIs)Recurrent vulvovaginal candidiasis (RVVCs)Trained immunity-based vaccines (TIbVs)Candida albicans V132Polybacterial preparation MV140InmunologíaBioquímica (Química)Biología molecular (Química)Bioquímica (Farmacia)2412 Inmunología2302 Bioquímica2403 BioquímicaRecurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ– and IL-17A–producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.FrontiersUniversidad Complutense de Madrid20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/95337reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/953372026-06-02T12:44:21Z
dc.title.none.fl_str_mv A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
title A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
spellingShingle A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
Martín De La Cruz, Leticia
577.1
Dendritic cells
Recurrent urinary tract infections (RUTIs)
Recurrent vulvovaginal candidiasis (RVVCs)
Trained immunity-based vaccines (TIbVs)
Candida albicans V132
Polybacterial preparation MV140
Inmunología
Bioquímica (Química)
Biología molecular (Química)
Bioquímica (Farmacia)
2412 Inmunología
2302 Bioquímica
2403 Bioquímica
title_short A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
title_full A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
title_fullStr A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
title_full_unstemmed A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
title_sort A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
dc.creator.none.fl_str_mv Martín De La Cruz, Leticia
Sevilla Ortega, Carmen
Benito Villalvilla, Cristina
Díez Rivero, Carmen
Sánchez Ramón, Silvia María
Subiza Garrido-Lestache, José Luis
Palomares Gracia, Óscar
author Martín De La Cruz, Leticia
author_facet Martín De La Cruz, Leticia
Sevilla Ortega, Carmen
Benito Villalvilla, Cristina
Díez Rivero, Carmen
Sánchez Ramón, Silvia María
Subiza Garrido-Lestache, José Luis
Palomares Gracia, Óscar
author_role author
author2 Sevilla Ortega, Carmen
Benito Villalvilla, Cristina
Díez Rivero, Carmen
Sánchez Ramón, Silvia María
Subiza Garrido-Lestache, José Luis
Palomares Gracia, Óscar
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 577.1
Dendritic cells
Recurrent urinary tract infections (RUTIs)
Recurrent vulvovaginal candidiasis (RVVCs)
Trained immunity-based vaccines (TIbVs)
Candida albicans V132
Polybacterial preparation MV140
Inmunología
Bioquímica (Química)
Biología molecular (Química)
Bioquímica (Farmacia)
2412 Inmunología
2302 Bioquímica
2403 Bioquímica
topic 577.1
Dendritic cells
Recurrent urinary tract infections (RUTIs)
Recurrent vulvovaginal candidiasis (RVVCs)
Trained immunity-based vaccines (TIbVs)
Candida albicans V132
Polybacterial preparation MV140
Inmunología
Bioquímica (Química)
Biología molecular (Química)
Bioquímica (Farmacia)
2412 Inmunología
2302 Bioquímica
2403 Bioquímica
description Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ– and IL-17A–producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/95337
url https://hdl.handle.net/20.500.14352/95337
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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