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Vaccination with Mincle agonist UM-1098 and mycobacterial antigens induces protective Th1 and Th17 responses.
Rungelrath, Viktoria; Ahmed, Mushtaq; Hicks, Linda; Miller, Shannon M; Ryter, Kendal T; Montgomery, Kyle; Ettenger, George; Riffey, Alexander; Abdelwahab, Walid M; Khader, Shabaana Abdul; Evans, Jay T.
Afiliación
  • Rungelrath V; Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59812, USA.
  • Ahmed M; Department of Biomedical & Pharmaceutical Sciences, University of Montana, Missoula, MT, 59812, USA.
  • Hicks L; Department of Microbiology, University of Chicago, 920 E. 58th St., Chicago, IL, 60637, USA.
  • Miller SM; Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59812, USA.
  • Ryter KT; Department of Biomedical & Pharmaceutical Sciences, University of Montana, Missoula, MT, 59812, USA.
  • Montgomery K; Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59812, USA.
  • Ettenger G; Department of Biomedical & Pharmaceutical Sciences, University of Montana, Missoula, MT, 59812, USA.
  • Riffey A; Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59812, USA.
  • Abdelwahab WM; Department of Biomedical & Pharmaceutical Sciences, University of Montana, Missoula, MT, 59812, USA.
  • Khader SA; Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59812, USA.
  • Evans JT; Department of Biomedical & Pharmaceutical Sciences, University of Montana, Missoula, MT, 59812, USA.
NPJ Vaccines ; 9(1): 100, 2024 Jun 06.
Article en En | MEDLINE | ID: mdl-38844494
ABSTRACT
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the top infectious killers in the world. The only licensed vaccine against TB, Bacille Calmette-Guérin (BCG), provides variable protection against pulmonary TB, especially in adults. Hence, novel TB vaccine approaches are urgently needed. Both Th1 and Th17 responses are necessary for protection against TB, yet effective adjuvants and vaccine delivery systems for inducing robust Th1 and Th17 immunity are lacking. Herein we describe a synthetic Mincle agonist, UM-1098, and a silica nanoparticle delivery system that drives Th1/Th17 responses to Mtb antigens. Stimulation of human peripheral blood mononuclear cells (hPBMCs) with UM-1098 induced high levels of Th17 polarizing cytokines IL-6, IL-1ß, IL-23 as well as IL-12p70, IL-4 and TNF-α in vitro. PBMCs from both C57BL/6 and BALB/c mice responded with a similar cytokine pattern in vitro and in vivo. Importantly, intramuscular (I.M.) vaccination with UM-1098-adjuvanted TB antigen M72 resulted in significantly higher antigen-specific IFN-γ and IL-17A levels in C57BL/6 wt mice than Mincle KO mice. Vaccination of C57BL/6 wt mice with immunodominant Mtb antigens ESAT6/Ag85B or M72 resulted in predominantly Th1 and Th17 responses and induced antigen-specific serum antibodies. Notably, in a virulent Mtb challenge model, vaccination with UM-1098 adjuvanted ESAT6/Ag85B or M72 significantly reduced lung bacterial burden when compared with unvaccinated mice and protection occurred in the absence of pulmonary inflammation. These data demonstrate that the synthetic Mincle agonist UM-1098 induces strong Th1 and Th17 immunity after vaccination with Mtb antigens and provides protection against Mtb infection in mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Vaccines Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Vaccines Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido