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MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates
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MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates
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Journal Article
MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates
2024
Overview
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.
There is a requirement for improved adjuvants to improve responses to vaccines, including adjuvants that induce Th17 cells. Here, the authors use a MINCLE and TLR9 agonist-based vaccine adjuvant and show induction of Th17 and mucosal immune responses to vaccine recall antigens in mice and non-human primate models of vaccination.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/21
/ 13/31
/ 38/91
/ 59/78
/ 64/60
/ 82/83
/ Adaptor Proteins, Vesicular Transport - immunology
/ Adaptor Proteins, Vesicular Transport - metabolism
/ Adjuvants, Immunologic - administration & dosage
/ Adjuvants, Immunologic - pharmacology
/ Agonists
/ Animals
/ Antigens
/ Female
/ Humanities and Social Sciences
/ Immunologic Memory - drug effects
/ Immunologic Memory - immunology
/ Membrane Proteins - agonists
/ Membrane Proteins - immunology
/ Mice
/ Mycobacterium tuberculosis - immunology
/ Primates
/ Recall
/ Science
/ Toll-Like Receptor 9 - agonists
/ Toll-Like Receptor 9 - immunology
/ Tuberculosis Vaccines - administration & dosage
/ Tuberculosis Vaccines - immunology
/ Vaccines
