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Updated: Jun 10, 2025
Determination of Vaccine Immunogenicity Using Bovine Monocyte-Derived Dendritic Cells
Published on: May 19, 2023
MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human
Joshua S Woodworth1, Vanessa Contreras2, Dennis Christensen3
1Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen, Denmark. jow@ssi.dk.
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.
Insights
A novel liposomal adjuvant, CAF®10b, effectively induces Th1 and Th17 immune responses in both mice and non-human primates. This new adjuvant shows promise for developing vaccines against challenging diseases.
Area of Science:
- Immunology
- Vaccinology
- Adjuvant Development
Background:
- Current vaccine development is limited by a lack of human-compatible adjuvants.
- Existing adjuvants do not induce T-helper 17 (Th17) cells, crucial for certain immune responses.
Purpose of the Study:
- To develop and evaluate a novel liposomal adjuvant, CAF®10b, for its ability to induce robust immune responses.
- To assess the species-specific effects of adjuvant composition in preclinical models.
Main Methods:
- CAF®10b was formulated with Mincle and Toll-like receptor 9 agonists.
- Comparative studies were conducted in mice and non-human primates using CAF®10b and existing CAF® adjuvants.
- Immune responses (Th1, Th17, antibody) and protection against Mycobacterium tuberculosis were assessed.
Main Results:
- CAF®10b induced Th1 and Th17 responses and protection against tuberculosis in mice.
- In non-human primates, CAF®10b elicited strong Th1 and Th17 responses lasting over six months.
- Robust memory antibody, Th1, and Th17 responses were observed across species via non-mucosal immunization.
Conclusions:
- CAF®10b is a potent adjuvant capable of inducing significant Th1 and Th17 immune responses.
- The findings support CAF®10b's potential for developing effective vaccines against difficult-to-target diseases.
- Adjuvant composition influences species-specific immune outcomes, highlighting the importance of tailored adjuvant design.
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