MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates
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.
Authors
- Nathalie Dereuddre‐Bosquet (ORCID: https://orcid.org/0000-0001-6682-6313)
- Nidhal Kahlaoui (ORCID: https://orcid.org/0000-0003-4784-0819)
- Joshua S. Woodworth (ORCID: https://orcid.org/0000-0002-0771-9056)
- Ann-Kathrin Stein
- Roger Le Grand (ORCID: https://orcid.org/0000-0002-4928-4484)
- Dennis Christensen (ORCID: https://orcid.org/0000-0003-2382-8639)
- Julie Morin (ORCID: https://orcid.org/0000-0001-9601-4359)
- Anne-Sophie Gallouët
- Frank Follmann (ORCID: https://orcid.org/0000-0002-8373-7774)
- Gabriel Kristian Pedersen (ORCID: https://orcid.org/0000-0001-6872-3975)
- Thibaut Naninck
- Sébastien Langlois
- Ming Liu Olsen
- Ida Rosenkrands (ORCID: https://orcid.org/0000-0003-0085-7883)
- Rasmus J. Mortensen (ORCID: https://orcid.org/0000-0003-0177-3032)
- Wesley Gros
- Grith Krøyer Wood
- Emma Burban (ORCID: https://orcid.org/0009-0006-3373-2891)
- Vanessa Contreras
- Thomas Lindenstrøm (ORCID: https://orcid.org/0000-0002-7162-8124)
- Tu Hu (ORCID: https://orcid.org/0000-0002-4635-4117)
- Candie Joly
Institutions
- Statens Serum Institut (DK)
- Inserm (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Paris-Saclay (FR)
- CEA Paris-Saclay (FR)
- Infectious Disease Models and Innovative Therapies (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1038/s41467-024-52863-9
- Citations
- 11
- Primary Topic
- Immune responses and vaccinations
- Type
- article
- Field-Weighted Citation Impact
- 2.65
Funders
- Agence Nationale de la Recherche
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases