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

Cell Reports (May 2018)

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

Journal volume & issue: Vol. 23, no. 5
pp. 1435 – 1447

Abstract

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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

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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