MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates

Joshua S. Woodworth (), Vanessa Contreras, Dennis Christensen, Thibaut Naninck, Nidhal Kahlaoui, Anne-Sophie Gallouët, Sébastien Langlois, Emma Burban, Candie Joly, Wesley Gros, Nathalie Dereuddre-Bosquet, Julie Morin, Ming Liu Olsen, Ida Rosenkrands, Ann-Kathrin Stein, Grith Krøyer Wood, Frank Follmann, Thomas Lindenstrøm, Tu Hu, Roger Le Grand, Gabriel Kristian Pedersen and Rasmus Mortensen ()
Additional contact information
Joshua S. Woodworth: Statens Serum Institut
Vanessa Contreras: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Dennis Christensen: Statens Serum Institut
Thibaut Naninck: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Nidhal Kahlaoui: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Anne-Sophie Gallouët: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Sébastien Langlois: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Emma Burban: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Candie Joly: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Wesley Gros: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Nathalie Dereuddre-Bosquet: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Julie Morin: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Ming Liu Olsen: Statens Serum Institut
Ida Rosenkrands: Statens Serum Institut
Ann-Kathrin Stein: Statens Serum Institut
Grith Krøyer Wood: Statens Serum Institut
Frank Follmann: Statens Serum Institut
Thomas Lindenstrøm: Statens Serum Institut
Tu Hu: Statens Serum Institut
Roger Le Grand: hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184)
Gabriel Kristian Pedersen: Statens Serum Institut
Rasmus Mortensen: Statens Serum Institut

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.

Date: 2024
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DOI: 10.1038/s41467-024-52863-9

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