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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Joshua S. Woodworth & Vanessa Contreras & Dennis Christensen & Thibaut Naninck & Nidhal Kahlaoui & Anne-Sophie Gallouët & Sébastien Langlois & Emma Burban & Candie Joly & Wesley Gros & Nathalie Dereud, 2024. "MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52863-9
    DOI: 10.1038/s41467-024-52863-9
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