CL429 VacciGrade™ - TLR2 & NOD2-based Adjuvant

CL429 is a chimeric compound that stimulates both TLR2 and NOD2. This compound is composed of murabutide (NOD2 ligand) covalently linked to Pam2C (TLR2 ligand) via a spacer [1].

NOD2 is highly expressed at the mucosal level [2, 3] and its activation induces the production of proinflammatory cytokines and autophagy [4, 5].

TLR2 appears to have a special role in T cell polarization and differentiation [6], mucosal homing receptor expression, and IgA production by human B cells [7].

CL429 was shown to induce synergistic human DC maturation in vitro and to significantly enhance both systemic and mucosal immunity against a vaccine antigen [1].

The very potent adjuvant activity of CL429 is associated with no apparent toxicity. This activity seems to be mediated by an optimal DC maturation process, which induces strong B and T cell stimulation and autophagy [1].

1. Pavot V. et al., 2014. Cutting edge: New chimeric NOD2/TLR2 adjuvant drastically increases vaccine immunogenicity. J Immunol. 193(12):5781-5.
2. Geddes K. et al., 2009. Unleashing the therapeutic potential of NOD-like receptors. Nat Rev Drug Discov. 8(6):465-79.
3. Kobayashi KS. et al., 2005. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 307(5710):731-4.
4. Rubino SJ. et al., 2012. Nod-like receptors in the control of intestinal inflammation. Curr Opin Immunol. 24(4):398-404.
5. Cooney R. et al., 2010. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med. 16(1):90-7.
6. Borrello S. et al., 2011. TLR2: a crossroads between infections and autoimmunity? Int J Immunopathol Pharmacol. 24(3):549-56.
7. Liang Y. et al., 2011. Toll-like receptor 2 induces mucosal homing receptor expression and IgA production by human B cells. Clin Immunol. 138(1):33-40.