Effect of AMP-dT on lymph node immune response in rhesus macaque

Presently, there is an acute need for effective adjuvants that safely induce durable and balanced humoral and cellular responses. Here, we engineered a class of Amphiphile (AMP)-modified, immunostimulatory DNA-adjuvants designed for targeted delivery to lymph nodes and enhanced stimulation of TANK-binding kinase 1 (TBK1)-mediated danger-sensing pathways to generate strong adaptive immunity and long-term memory with potent recall potential.

AMP-DNA adjuvants induced robust interferon type-I (IFN-I)-driven inflammatory environments in mouse and non-human primate (NHP) lymph nodes, leading to significantly enhanced cytokine secretion by polyfunctional CD8+ and CD4+ T cells in multiple tissues, as well as strongly elevated TH1-associated and neutralizing antibody responses, in the absence of systemic toxicity. These results demonstrate that AMP-modification enables lymph node-targeted DNA-adjuvants to potently activate IFN-I-signaling to generate substantial cellular and humoral responses crucial for vaccine efficacy.