STING-Activating Adjuvants Elicit a Th17 Immune Response and Protect against Mycobacterium tuberculosis Infection
Erik Van Dis,
Kimberly M. Sogi,
Chris S. Rae,
Kelsey E. Sivick,
Natalie H. Surh,
Meredith L. Leong,
David B. Kanne,
Ken Metchette,
Justin J. Leong,
Jacob R. Bruml,
Vivian Chen,
Kartoosh Heydari,
Nathalie Cadieux,
Tom Evans,
Sarah M. McWhirter,
Thomas W. Dubensky, Jr.,
Daniel A. Portnoy,
Sarah A. Stanley
Affiliations
Erik Van Dis
Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA
Kimberly M. Sogi
School of Public Health, Division of Infectious Disease and Vaccinology, University of California, Berkeley, Berkeley, CA 94720, USA
Chris S. Rae
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Kelsey E. Sivick
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Natalie H. Surh
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Meredith L. Leong
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
David B. Kanne
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Ken Metchette
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Justin J. Leong
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Jacob R. Bruml
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Vivian Chen
School of Public Health, Division of Infectious Disease and Vaccinology, University of California, Berkeley, Berkeley, CA 94720, USA
Kartoosh Heydari
LKS Flow Cytometry Core, Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA
Nathalie Cadieux
Aeras, 1405 Research Blvd., Rockville, MD 20850, USA
Tom Evans
Vaccitech Limited, King Charles House, Park End Street, Oxford OX1 1JD, UK
Sarah M. McWhirter
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Thomas W. Dubensky, Jr.
Aduro Biotech, Inc., 740 Heinz Avenue, Berkeley, CA 94710, USA
Daniel A. Portnoy
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
Sarah A. Stanley
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; Corresponding author
Summary: 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. : Van Dis et al. demonstrate that STING-activating cyclic dinucleotides provide significant protection when used as adjuvants in a protein subunit vaccine against Mycobacterium tuberculosis and show that mucosal administration of this vaccine elicits a Th17 immune response that correlates with enhanced protection. Keywords: Mycobacterium tuberculosis, vaccine adjuvant, cyclic dinucleotides, Th17
