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The STING ligand cGAMP potentiates the efficacy of vaccine-induced CD8+ T cells
Alice Gutjahr, … , Stéphane Paul, Victor Appay
Alice Gutjahr, … , Stéphane Paul, Victor Appay
Published April 4, 2019
Citation Information: JCI Insight. 2019;4(7):e125107. https://doi.org/10.1172/jci.insight.125107.
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Research Article Vaccines

The STING ligand cGAMP potentiates the efficacy of vaccine-induced CD8+ T cells

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Abstract

Pathogen recognition receptor (PRR) agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. Using an original in vitro approach to prime naive precursors from unfractionated human peripheral blood mononuclear cells, we assessed the influence of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), a ligand for the stimulator of interferon genes (STING), on the induction of antigen-specific CD8+ T cells. We found that 2′3′-cGAMP and 3′3′-cGAMP were especially potent adjuvants in this system, driving the expansion and maturation of functionally replete antigen-specific CD8+ T cells via the induction of type I IFNs. The biological relevance of these findings was confirmed in vivo using two mouse models, in which 2′3′-cGAMP–adjuvanted vaccination elicited protective antitumor or antiviral CD8+ T cell responses. These results identify particular isoforms of cGAMP as effective adjuvants that may find utility in the development of novel immunotherapies and vaccines.

Authors

Alice Gutjahr, Laura Papagno, Francesco Nicoli, Tomohiro Kanuma, Nozomi Kuse, Mariela Pires Cabral-Piccin, Nicolas Rochereau, Emma Gostick, Thierry Lioux, Eric Perouzel, David A. Price, Masafumi Takiguchi, Bernard Verrier, Takuya Yamamoto, Stéphane Paul, Victor Appay

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Figure 1

STING ligands enhance the induction of effector CD8+ T cells.

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STING ligands enhance the induction of effector CD8+ T cells.
(A) Left: ...
(A) Left: Representative flow cytometry data showing EV10-specific CD8+ T cells expanded in the presence of Flt3 ligand and various adjuvants. Cytokines: TNF, IL-1β, IL-7, and PGE2. Plots are gated on viable CD3+ events. Percentage values represent HLA-A2-EV10 tetramer+ cells among total CD8+ T cells. Right: Data summary. Each dot represents 1 HLA-A2+ donor per condition. The dotted line shows the mean percentage of HLA-A2–EV10 tetramer+ cells among total CD8+ T cells incubated with cytokines in the absence of peptide (n = 20). (B) Intracellular expression of T-bet among EV10-specific CD8+ T cells primed as in A. Left: Representative flow cytometry plots gated on viable HLA-A2–EV10 tetramer+ CD8+ T cells. The dotted line shows the limit for positive expression. Right: data summary. Each dot represents 1 HLA-A2+ donor per condition. (C) Intracellular expression of perforin and granzyme B among EV10-specific CD8+ T cells primed as in A. Details as in B. Horizontal bars indicate median values. P values are represented as circles with variable size and color intensity (Mann-Whitney U test).

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