A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates

一种新型佐剂配方可在非人类灵长类动物中诱导强大的 Th1/Th17 记忆和粘膜回忆反应

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作者:Joshua S Woodworth, Vanessa Contreras, Dennis Christensen, Thibaut Naninck, Nidhal Kahlaoui, Anne-Sophie Gallouët, Sébastien Langlois, Emma Burban, Candie Joly, Wesley Gros, Nathalie Dereuddre-Bosquet, Julie Morin, Ming Liu Olsen, Ida Rosenkrands, Ann-Kathrin Stein, Grith Krøyer Wood, Frank Follmann

Abstract

After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF®10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF®10b induced significantly increased antibody and cellular immune responses compared to previous CAF® adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF®10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF®10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.

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