NOD2 Ligand Induces Long Lasting Immunity and Amplifies Mucosal and Systemic Immune Responses after sub cutaneous immunization in mice

Most successful vaccines are able to induce persistent antibody responses that can last lifetime. Emerging evidences indicate that activation of immune cells through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) or NOD-like receptors (NLRs) may be critical mechanisms. Among PRRs, the use of TLR ligands as adjuvants is already largely described whereas the use of NLRs ligands remains largely unexplored regarding the induction of long lasting immunity.

The added value of encapsulation of NOD1 and NOD2 receptor ligands into Poly(Lactic Acid) (PLA) biodegradable nanocarriers to induce persistent antibody responses was explored. In vitro, NOD ligands encapsulated into PLA nanoparticles induced strong up-regulation of maturation markers and enhancement of proinflammatory cytokine secretion by DCs, with a better effect with NOD2 receptor ligands.

In vivo, co-injection of encapsulated NOD2 ligands, in mice, with PLA particles carrying Gag p24 HIV-1 antigen allow a 100 fold increase in antibody responses in comparison to Alum and induction of mucosal immune responses. The same study with gp140 HIV-1 glycoprotein show enhancement of antibody responses and induction of long-lasting immunity.

Our results provide a rational approach for broader application of particulate vaccines using encapsulated NODs receptor ligands as potent tools to induce long lasting immunity.