Covalently Conjugated NOD2/TLR7 Agonists Are Potent and Versatile Immune Potentiators

The success of vaccination with subunit vaccines often
relies on
the careful choice of adjuvants. There is great interest in developing
new adjuvants that can elicit a cellular immune response. Here, we
address this challenge by taking advantage of the synergistic cross-talk
between two pattern recognition receptors: nucleotide-binding oligomerization-domain-containing
protein 2 (NOD2) and Toll-like receptor 7 (TLR7). We designed two
conjugated NOD2/TLR7 agonists, which showed potent immunostimulatory
activities in human primary peripheral blood mononuclear cells and
murine bone-marrow-derived dendritic cells. One of these, 4, also generated a strong antigen-specific immune response in vivo, with a Th1-polarized profile. Importantly, our
study shows that novel NOD2/TLR7 agonists elicit sophisticated and
fine-tuned immune responses that are inaccessible to individual NOD2
and TLR7 agonists.