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

Nat Commun. 2024 Oct 17;15(1):8959. doi: 10.1038/s41467-024-52863-9.

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.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / immunology
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Adjuvants, Immunologic* / administration & dosage
  • Adjuvants, Immunologic* / pharmacology
  • Animals
  • Female
  • Immunologic Memory* / drug effects
  • Immunologic Memory* / immunology
  • Liposomes / immunology
  • Membrane Proteins / agonists
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology
  • Th1 Cells* / drug effects
  • Th1 Cells* / immunology
  • Th17 Cells* / drug effects
  • Th17 Cells* / immunology
  • Toll-Like Receptor 9* / agonists
  • Toll-Like Receptor 9* / immunology
  • Tuberculosis Vaccines / administration & dosage
  • Tuberculosis Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Toll-Like Receptor 9
  • Adaptor Proteins, Vesicular Transport
  • Tuberculosis Vaccines
  • Membrane Proteins
  • Liposomes