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STING-Activating Adjuvants Elicit a Th17 Immune Response and Protect against Mycobacterium tuberculosis Infection.
Van Dis, Erik; Sogi, Kimberly M; Rae, Chris S; Sivick, Kelsey E; Surh, Natalie H; Leong, Meredith L; Kanne, David B; Metchette, Ken; Leong, Justin J; Bruml, Jacob R; Chen, Vivian; Heydari, Kartoosh; Cadieux, Nathalie; Evans, Tom; McWhirter, Sarah M; Dubensky, Thomas W; Portnoy, Daniel A; Stanley, Sarah A.
Afiliación
  • Van Dis E; Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Sogi KM; School of Public Health, Division of Infectious Disease and Vaccinology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Rae CS; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Sivick KE; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Surh NH; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Leong ML; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Kanne DB; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Metchette K; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Leong JJ; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Bruml JR; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Chen V; School of Public Health, Division of Infectious Disease and Vaccinology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Heydari K; LKS Flow Cytometry Core, Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Cadieux N; Aeras, 1405 Research Blvd., Rockville, MD 20850, USA.
  • Evans T; Vaccitech Limited, King Charles House, Park End Street, Oxford OX1 1JD, UK.
  • McWhirter SM; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Dubensky TW; Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA.
  • Portnoy DA; Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA; School of Public Health, Division of Infectious Disease and Vaccinology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Stanley SA; Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA; School of Public Health, Division of Infectious Disease and Vaccinology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: sastanley@berkel
Cell Rep ; 23(5): 1435-1447, 2018 05 01.
Article en En | MEDLINE | ID: mdl-29719256
ABSTRACT
There are a limited number of adjuvants that elicit effective cell-based immunity required for protection against intracellular bacterial pathogens. Here, we report that STING-activating cyclic dinucleotides (CDNs) formulated in a protein subunit vaccine elicit long-lasting protective immunity to Mycobacterium tuberculosis in the mouse model. Subcutaneous administration of this vaccine provides equivalent protection to that of the live attenuated vaccine strain Bacille Calmette-Guérin (BCG). Protection is STING dependent but type I IFN independent and correlates with an increased frequency of a recently described subset of CXCR3-expressing T cells that localize to the lung parenchyma. Intranasal delivery results in superior protection compared with BCG, significantly boosts BCG-based immunity, and elicits both Th1 and Th17 immune responses, the latter of which correlates with enhanced protection. Thus, a CDN-adjuvanted protein subunit vaccine has the capability of eliciting a multi-faceted immune response that results in protection from infection by an intracellular pathogen.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis Pulmonar / Vacuna BCG / Adyuvantes Inmunológicos / Células Th17 / Proteínas de la Membrana / Mycobacterium tuberculosis Límite: Animals Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis Pulmonar / Vacuna BCG / Adyuvantes Inmunológicos / Células Th17 / Proteínas de la Membrana / Mycobacterium tuberculosis Límite: Animals Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos