Mucosal adjuvants

Abstract

Induction of immune responses following oral immunization is frequently dependent upon the co-administration of appropriate adjuvants that can initiate and support the transition from innate to adaptive immunity. The three bacterial products with the greatest potential to function as mucosal adjuvants are the ADP-ribosylating enterotoxins (cholera toxin and the heat-labile enterotoxin of Escherichia coli), synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN), and monophosphoryl lipid A (MPL). The mechanism of adjuvanticity of the ADP-ribosylating enterotoxins is the subject of considerable debate. Our own view is that adjuvanticity is an outcome and not an event. It is likely that these molecules exert their adjuvant function by interacting with a variety of cell types, including epithelial cells, dendritic cells, macrophages, and possibly B- and T-lymphocytes. The adjuvant activities of CpG and MPL are due to several different effects they have on innate and adaptive immune responses and both MPL and CpG act through MyD88-dependent and -independent pathways. This presentation will summarize the probable mechanisms of action of these diverse mucosal adjuvants and discuss potential synergy between these molecules for use in conjunction with plant-derived vaccines.

Functional Diversity of Heat-labile Toxins (LT) Produced by Enterotoxigenic Escherichia coli

“…LT derivatives are known to elicit balanced Th1/Th2 immune responses, whereas CT derivatives clearly favor Th2-biased responses (14). Our data show that mice immunized with LT4 favored a type 1-biased immune response when compared with mice immunized with LT1 and LTK4R, suggesting that amino acid residues at other positions, either at the A or B subunits, play a relevant role on the immunomodulatory properties of LT. A better understanding of the impact associated with specific residues involved in the immunomodulatory role of LT, as well as in inhibition of NF-B production (49), will certainly help gain knowledge of the molecular mechanisms associated with the adjuvant effects of these molecules.…”

“…Co-administration of LT with antigens results in increased production of antigen-specific mucosal (IgA) and systemic (IgG) antibodies as well as activation of T lymphocytes (11,12). To avoid the mucosal toxicity exhibited by the native toxin, different LT mutants with reduced toxic effect but partially preserved adjuvanticity were tested in the murine model (13,14). Among the several LT mutants generated under laboratory conditions, LTK63 and LTR72, with no or drastically reduced enzymatic activity, and LTR192G, lacking the trypsin cleavage site, have been intensively investigated as potential mucosal adjuvants in the mouse model (8,9,15).…”

Oral immunization against enterotoxigenic colibacillosis in weaned piglets by non-pathogenic Escherichia colistrain with K88 (F4) colonizing factors

“…It was demonstrated that the immunity occurred later than after the administration of a strain with colonizing factors F18ac in our previous experiments where piglets were protected against challenge with F18 positive ETEC on day 7 after combined immunization. It was proved in the second experiment when the infection with ETEC strain was performed on the third day after wean- It is likely that LT has adjuvant properties similarly like cholera toxin (Clements et al, 1988;Cheng et al, 1999;Freytag and Clements, 2005). The strain used in the present study did not produce LT.…”

Adjuvants for allergy vaccines

“…No synergy between fluticasone and SLiT was observed in humans when using distinct administration routes. activity) 49,50 (Table 1). These toxins were either co-administered, conjugated or fused with allergens.…”

“…These toxins were either co-administered, conjugated or fused with allergens. 49,50 TLR2 (e.g., Pam3CSK4) or TLR4 ligands (e.g., MPL and OM-294-BA-MP) were shown to strengthen Th1 and T Reg responses when used as adjuvants via the nasal or sublingual routes. [51][52][53][54] Similarly, dexamethasone associated with 1.25-dihydroxy vitamin D3 enhanced the efficacy of SLIT in a murine asthma model following induction of interleukin 10 production by immune cells, including dendritic cells and CD4 + T lymphocytes.…”