Modulation of adaptive immunity by different adjuvant–antigen combinations in mice lacking Nod2

Abstract

The mechanisms underlying adjuvant effects are under renewed scrutiny because of the enormous implications for vaccine development. Additionally, new low-toxicity adjuvants are sought to enhance vaccine formulations. Muramyl dipeptide (MDP) is a component of the peptidoglycan polymer and was shown to be an active but low-toxicity component of complete Freund's adjuvant, a powerful adjuvant composed of mycobacteria lysates in an oil emulsion. MDP activates cells primarily via the cytosolic NLR family member Nod2 and is therefore linked to the ability of adjuvants to enhance antibody production. Accordingly, we tested the adjuvant properties of the MDP-Nod2 pathway. We found that MDP, compared to the TLR agonist lipopolysaccharide, has minimal adjuvant properties for antibody production under a variety of immunization conditions. We also observed that the oil emulsion incomplete Freund's adjuvant (IFA) supplanted the requirements for the TLR pathway independent of the antigen. Surprisingly, we observed that Nod2 was required for an optimal IgG1 and IgG2c response in the absence of exogenous TLR or NLR agonists. Collectively, our results argue that oil emulsions deserve greater attention for their immunostimulatory properties.

Selection of Adjuvants for Enhanced Vaccine Potency

“…These compounds activate cells primarily via the cytosolic NLR family member NOD2 and therefore lead to enhancement of antibody production [401]. Peptidoglycan monomer (PGM), a natural compound of bacterial origin (Brevibacterium divaricatum), is a non-toxic, non-pyrogenic, water-soluble immunostimulator.…”

“…While muramyl peptides preferentially stimulate IgG1 production, the tetrasaccharide containing muramyl peptide induces additional production of IgG2b subclasses [404]. However, muramyl dipeptide (MDP), a component of the peptidoglycan polymer, has minimal adjuvant properties for antibody production compared to the TLR agonist lipopolysaccharide under a variety of immunization conditions [401].…”

Comparative study of structurally related peptidoglycan monomer and muramyl dipeptide on humoral IgG immune response to ovalbumin in mouse

“…IFA is an oil adjuvant without killed mycobacteria and therefore not reactogenic as CFA. There is a significant interest in revisiting the use of IFA for new vaccine development [45,46]. Addition of PGM to IFA, after the first booster, enhanced the IgG response that was comparable to the effect of CFA.…”

Status and future prospects of lipid-based particulate delivery systems as vaccine adjuvants and their combination with immunostimulators

“…MDP is an active but low-toxicity component of complete Freund's adjuvant. MDP has been used as an adjuvant and was suggested to induce humoral immune responses, but recent data suggest that MDP is a poor inducer of antibodies [71]. However, MDP might, in combination with antigen delivery systems, have attractive immune-activating effects.…”