Enhanced control of Mycobacterium Tuberculosis Extrapulmonary Dissemination in Mice by an Arabinomannan-protein Conjugate Vaccine

dc.creatorBaena García, Andres
dc.creatorPrados Rosales, Rafael
dc.creatorCarreño, Leandro
dc.creatorCheng, Tingting
dc.creatorBlanc, Caroline
dc.creatorWeinrick, Brian
dc.creatorMalek, Adel
dc.creatorLowary, Todd L.
dc.date2022-05-09T21:42:19Z
dc.date2022-05-09T21:42:19Z
dc.date2017
dc.date.accessioned2023-08-28T20:48:06Z
dc.date.available2023-08-28T20:48:06Z
dc.identifier1553-7366
dc.identifierhttp://hdl.handle.net/10495/28302
dc.identifier10.1371/journal.ppat.1006250
dc.identifier1553-7374
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8484446
dc.descriptionABSTRACT: Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB) and each formulation attempts to elicit protection by enhancement of cellmediated immunity (CMI). In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM) to either Mtb Ag85b or B. anthracis protective antigen (PA). Further, we studied their immunogenicity by ELISA and AM glycan microarrays and protection efficacy in mice. Immunization with either Abg85b-AM or PA-AM conjugates elicited an AM-specific antibody response in mice. AM binding antibodies stimulated transcriptional changes in Mtb. Sera from AM conjugate immunized mice reacted against a broad spectrum of AM structural variants and specifically recognized arabinan fragments. Conjugate vaccine immunized mice infected with Mtb had lower bacterial numbers in lungs and spleen, and lived longer than control mice. These findings provide additional evidence that humoral immunity can contribute to protection against Mtb.
dc.description0008639
dc.format28
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.publisherGrupo de Inmunología Celular e Inmunogenética
dc.publisherSan Francisco, Estados Unidos
dc.relationPLoS Pathog.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.subjectTuberculosis
dc.subjectMycobacterium tuberculosis
dc.subjectVaccines, Conjugate
dc.subjectVacunas Conjugadas
dc.titleEnhanced control of Mycobacterium Tuberculosis Extrapulmonary Dissemination in Mice by an Arabinomannan-protein Conjugate Vaccine
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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