Nature Communications (Oct 2024)

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,
  • Rasmus Mortensen

DOI
https://doi.org/10.1038/s41467-024-52863-9
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 16

Abstract

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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.