1. MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates.
- Author
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Woodworth JS, Contreras V, Christensen D, Naninck T, Kahlaoui N, Gallouët AS, Langlois S, Burban E, Joly C, Gros W, Dereuddre-Bosquet N, Morin J, Liu Olsen M, Rosenkrands I, Stein AK, Krøyer Wood G, Follmann F, Lindenstrøm T, Hu T, Le Grand R, Pedersen GK, and Mortensen R
- Subjects
- Animals, Mice, Female, Mice, Inbred C57BL, Mycobacterium tuberculosis immunology, Adaptor Proteins, Vesicular Transport metabolism, Adaptor Proteins, Vesicular Transport immunology, Tuberculosis Vaccines immunology, Tuberculosis Vaccines administration & dosage, Membrane Proteins agonists, Membrane Proteins immunology, Liposomes immunology, Th17 Cells immunology, Th17 Cells drug effects, Th1 Cells immunology, Th1 Cells drug effects, Adjuvants, Immunologic pharmacology, Adjuvants, Immunologic administration & dosage, Toll-Like Receptor 9 agonists, Toll-Like Receptor 9 immunology, Immunologic Memory drug effects, Immunologic Memory immunology
- 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., (© 2024. The Author(s).)
- Published
- 2024
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