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

Publication date: Oct 17, 2024

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(R)10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF(R) 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(R)10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF(R)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(R)10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.

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Concepts Keywords
Agonists Adjuvants, Immunologic
Higher Adjuvants, Immunologic
Mice Animals
Mycobacterium Female
Vaccines Immunologic Memory
Liposomes
Liposomes
Membrane Proteins
Membrane Proteins
Mice
Mycobacterium tuberculosis
Th1 Cells
Th17 Cells
Toll-Like Receptor 9
Toll-Like Receptor 9
Tuberculosis Vaccines
Tuberculosis Vaccines

Semantics

Type Source Name
disease IDO quality
pathway REACTOME Infection with Mycobacterium tuberculosis
disease MESH infection
disease MESH hepatitis
disease MESH influenza
disease MESH malaria
pathway KEGG Malaria
disease MESH shingles
drug DRUGBANK Diethylstilbestrol
disease MESH bacterial infections
drug DRUGBANK Distearyldimonium
drug DRUGBANK Trehalose
drug DRUGBANK Coenzyme M
drug DRUGBANK Aluminum hydroxide
disease IDO cell
drug DRUGBANK Spinosad
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH respiratory infections
disease MESH inflammation
disease IDO assay
disease IDO blood
drug DRUGBANK Pidolic Acid
disease IDO biological process
drug DRUGBANK Dimercaprol
disease MESH hypersensitivity
disease IDO protein
disease IDO production
disease IDO site
drug DRUGBANK Methylergometrine
drug DRUGBANK BCG vaccine
disease IDO pathogen

Original Article

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