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Review
. 2014 Aug 26;111(34):12294-9.
doi: 10.1073/pnas.1400478111. Epub 2014 Aug 18.

Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants

Charles Maisonneuve  1 , Sylvie Bertholet  2 , Dana J Philpott  3 , Ennio De Gregorio  2
Affiliations
Review

Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants

Charles Maisonneuve et al. Proc Natl Acad Sci U S A. .

Abstract

Innate immunity confers an immediate nonspecific mechanism of microbial recognition through germ line-encoded pattern recognition receptors (PRRs). Of these, Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) have shaped our current understanding of innate regulation of adaptive immunity. It is now recognized that PRRs are paramount in instructing an appropriate adaptive immune response. Their ligands have been the focus of adjuvant research with the goal of generating modern vaccine combinations tailored to specific pathogens. In this review we will highlight the recent findings in the field of adjuvant research with a particular focus on the potential of TLR and NLR ligands as adjuvants and their influence on adaptive immune responses.

Keywords: NLRP3; NOD1; NOD2; TLR4 alum.

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Conflict of interest statement

Conflict of interest statement: S.B. and E.D.G. are full-time employees of Novartis Vaccines and Diagnostics.

Figures

Fig. 1.
Fig. 1.
Using PRR agonists to modulate the CD4 T-cell response. APCs expressing PRRs, such as TLRs and NLRs, can take up the antigen and provide key cytokines to prime naïve CD4 T cells toward specific TH phenotypes characterized by their cytokine profile. TH1 cells are induced by IL-12, and produce IFN-γ against viral, intracellular bacterial, or parasitic infections. TH2 cells are induced by TSLP-expressing and IL-33–producing DCs and are characterized by the production of IL-4, IL-5, IL-6, IL-10, and IL-13 against extracellular pathogens (–12). Finally, TH17 cells producing IL-17 are induced in the presence of IL-23 and IL-6. TLR stimulation mediates TH1 and TH17 responses (14), whereas NOD1 and NOD2 stimulation within the nonhematopoietic compartment induces a predominant TH2 polarized response in vivo. Interestingly, costimulation with TLRs and NLRs synergizes to elicit TH1 and TH17 immune responses (8, 13, 16).
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