Adjuvants adjuvant activity

Kohn, J., Niemi, S. M., Albert, E. C., Murphy, J. C., Danger, R., and Fox, J. G., Single step immunization using a controlled release, biodegradable polymer with sustained adjuvant activity, J. Immunol. Meth., 95. 31-38, 1986. 

LIPOSPHERES AS CARRIERS OF ADJUVANTS 5.4.1 Adjuvant Activity of Lipid A... 

The results presented in this chapter demonstrate that enhanced immunogenic efficacy can be achieved by using liposphere-based formulations, indicating the potential usefulness of lipospheres in the formulation of human and veterinary vaccines. The liposphere approach employs the fat-lipid environment to achieve several goals to serve as a carrier to protect the antigen, to serve as a depot, and to provide a surface interphase necessary for adjuvant activity. The ability to provide different surface... 

It is reasonable to presume that the immunogenic and adjuvant activity of lipospheres may be the result of a combination of factors. These factors may include a focused and enhanced delivery of the antigen to an antigen-presenting cell (macrophage) and protection of the antigen from metabolic destruction at other sites in the body that do no participate in the immune response. 

The liposphere delivery system as a fat-based adjuvant formulation may both provide the surface interface necessary for solubilization and proper orientation of the adjuvant-active material, and provide potential carriers for vaccines, which may allow better position for processing and presentation of the incorporated antigens, resulting in enhanced immunogenicity. 

Hunter R., S.F., F. Kezdy, The Adjuvant Activity of Nonionic Block Polymer Surfactants I. The Role of Hydrophile-Lipophile Balance, Journal of Immunology. 127, 1244, 1981. 

Ellouz, F. et al., Minimal structural requirements for adjuvant activity of bacterial pepti-doglycan derivatives, Biochem. Biophys. Res Commun., 59, 1317, 1974. 

De Haar, C., et al., Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model, Toxicol. Sci. 87, 2, 409, 2005. 

Takafuji, S., et al., Diesel-exhaust particulates inoculated by the intranasal route have an adjuvant activity for IgE production in mice, J. Allergy Clin. Immunol., 79, 639, 1987. 

Yoshikawa, M., Morikawa, T., Yashiro, K., Murakami, T., Yamahara, J., and Matsuda, H. (2001). Bioactive saponins and glycosides. XIX. Notoginseng (3) Immunological adjuvant activity of notoginsenosides and related saponins Structures of notoginsenosides-L, -M, and -N from the roots of Panax notoginseng (Burk.) F. H. Chen. Chem. Pharm. Bull. 49, 1452-1456. 

Krishnan L, et al. The potent adjuvant activity of archaeosomes correlates to the recruitment and activation of macrophages and dendritic cells in vivo. J Immunol 2001 166 1885. 

Hunter R, Strickland F, Kezdy F (1981) The adjuvant activity of nonionic block polymer surfactants. J Immunol 127 1244-1250... 

Two processes are suggested to be of importance in the induction of T cell sensitization by chemicals (i) the formation of neoantigens (i.e., cryptic epitopes or hapten-carrier conjugates) (ii) the stimulation of innate immune processes (i.e., adjuvant activity or induction of danger signals reviewed by Uetrecht [64]). The... 

A wide variety of materials have been explored for their adjuvant activity, although not all are equally effective or nontoxic, especially in humans. Alum and other aluminum salts were first recognized in 1926 and remain the most effective agents licensed for human use by the FDA, although some French products also use calcium phosphate. However, in recent years it has become evident that new and improved vaccine adjuvants are needed. 

The most prominent mixed Ai/A2 receptor antagonist is caffeine which is currently used clinically as an adjunctive analgesic in combination with acetaminophen and other NSAIDs. Its adjuvant activity has been demonstrated in both clinical and preclinical studies and it is extremely successful on the OTC market. Other mixed Ai/A2 receptor antagonist are currently being investigated in preclinical studies (Akahane et al. (Fujisawa Pharm Co), 2001). 

When crude endotoxin from the heptose-less mutant of Salmonella typhimurium is combined with trehalose dimycolate from mycobacteria in oil droplets and injected directly into established tumors (line 10 hepatocellular carcinoma) in syngeneic guinea pigs, rapid regression of the tumors occurs and over 90% of the animals are cured. The three required components for activity in this tumor model are (a) the endotoxin (b) the mycobacterial adjuvant, trehalose dimycolate and (c) a compound satisfying the minimal structural requirement (muramyl dipeptide) for adjuvant activity by bacterial cell wall materials. The mycobacterial cell wall skeleton is able to replace the latter two components. 

A wide variety of novel approaches for the development of mucosal immune responses by administration of antigens in different delivery systems have been investigated, in many cases, with considerable success. These approaches include (1) the coadministration of immunogens with adjuvants active at the mucosal surface, (2) the coupling of immunogens to carrier molecules that promote their uptake at the mucosal inductive site, and (3) the expression of antigens in live attenuated bacterial or viral vectors, which can promote the colonization of mucosal tissue and the incorporation of antigens into a variety of microparticulate and adhesive vehicles, which are taken up in mucosal inductive sites. 

Roy et al. 1999). There are four basic DNA-based immunotherapeutic approaches immunization with DNA gene vaccines, allergen mixed with immu-nostimulatory oligodeoxynucleotide (ISS-ODN), allergen-ISS-ODN conjugates, and immunomodulation with ISS-ODN alone. ISS-ODN or CpG motifs provide Thl adjuvant activity for the immune response that developed toward the gene product (Sato et al. 1996). 

Interactions between lipids and receptors for structurally conserved pathogen-associated molecular patterns, most commonly the Toll-like receptors (TLRs), have been studied in detail for their involvement in adjuvant activity. TLRs appear to play an important role in the functioning of many adjuvants and the most important TLRs for lipopeptide or glycolipopeptide vaccines are TLR1, TLR2, TLR4, and TLR6 (van Duin et al. 2006). 

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