Peptide adjuvant

Nagai, Y., K. Akiyama, S. Kotani, Y. Watanabe, T. Shimono, T. Shiba, and S. Kusumoto Structural specificity of synthetic peptide adjuvant for induction of experimental allergic encephalomyelitis. Cell. Immunol. 35, 168 (1978). 

The nasal tissue is highly vascularized and provides efficient systemic absorption. Compared with oral or subcutaneous administration, nasal administration enhances bioavailability and improves safety and efficacy. Chitosan enhances the absorption of proteins and peptide drugs across nasal and intestinal epithelia. Gogev et al. demonstrated that the soluble formulation of glycol chitosan has potential usefulness as an intranasal adjuvant for recombinant viral vector vaccines in cattle [276]. 

A human contraceptive vaccine based on lactide polymers is currently being developed. The antigen is a 37-amino-acid peptide of B-HCG conjugated to diphtheria toxoid. The antigen is administered wtih microencapsulated muramyl dipeptide as an adjuvant. Studies in rabbits have shown 9-12 months of elevated antibody liter following... 

Halloran MM, Woods JM, Stricter RM, et al. The role of an epithelial neutrophilactivating peptide-78-like protein in rat adjuvant-induced arthritis. J Immunol 1999 162(12) 7492-7500. 

Fig. 15 Induction of cellular immunity by subcutaneous immunization with OVA-encapsulating y-PGA-Phe nanoparticles. Mice were subcutaneously immunized one time with OVA alone (10 pg), 10 pg of OVA and 100 pg of NPs (OVA-NPs), 10 pg of OVA and 100 pL of complete Freund s adjuvant (OVA + CFA), or PBS (control). Splenocytes were obtained from the immunized mice on day 10 after the immunization and stimulated with the OVA peptide. The number of IFN-y-producing cells was measured by enzyme-linked immunospot assay. SFU spot forming units...

One particularly novel carrier was reported to consist of 50-70 nm colloidal gold particles of the type often used in cytochemical labeling techniques for microscopy (Pow and Crook, 1993) (Chapter 24). Adsorption of peptide antigens onto gold and subsequent injection of the complex into rabbits in an adjuvant mixture resulted in rapid production of antibody of extremely high titer. The resultant antibodies could be used in immunocytochemistry at dilutions from l-in-250,000 down to l-in-1,000,000, which is orders-of-magnitude beyond the dilutions typically used with lower-titer antibodies. 

Edelman, R. 2002. The development and use of vaccine adjuvants. Molecular Biotechnology 21(2), 129-148. Francis, J. and Larche, M. 2005. Peptide-based vaccination where do we stand Current Opinion in Allergy and Clinical Immunology 5(6), 537-543. 

Second, we described the successful outcomes of Ap immunotherapy in mutant mice with Ap amyloidosis. Unfortunately, in humans, although Phase 1 trials with Ap peptide and adjuvant vaccination were not associated with any adverse events, Phase 2 trials were suspended because of severe adverse reactions (meningoencephalitis) in a subset of patients [79,90]. The pathology in a single case, consistent with T-cell meningitis [90], was interpreted to show some clearance of Ap deposits, yet these regions... 

Stern, B.V., Boehm, B.O., and Tary-Lehmann, M., Vaccination with tumor peptide in CpG adjuvant protects via IFN-gamma-dependent CD4 cell immunity, J Immunol, 168, 6099, 2002. 

A frequently used strategy to couple peptides to the surface of liposomes consists in the use hydrophobic/amphipathic anchors that are functionalized with maleimide or bromoacetyl groups, i.e., thiol-reactive functions, which give by reaction with HS-peptides very stable thioether linkages. These functions are conveniently introduced into hydrophobic anchors such as phospholipids, e.g., PE (9,10), the adjuvant PamsCAG (11) or cholesterol... 

Finally, besides conventional liposomes that are made from natural (e.g., egg yolk and soybean) or synthetic phospholipids, novel liposomes called archaeosomes that are prepared from the polar ether lipids extracted from various archaeobacteria proved also interesting for the design of vaccines as peptide antigen carriers (71) and as powerful self-adjuvanting vaccine delivery vesicles that promote both humoral and cell-mediated immunity (72). Related to this, one can mention that pseudopeptides, which are less prone to proteolysis when conjugated to liposomes, were also competent in triggering a humoral immune response (73). 

Figure 4 Design of a chemically defined diepitope liposomal anticancer vaccine. Small unilamellar liposomes (PC/PG/Chol 75/20/50 molar ratio diameter 65nm) containing 5mol% of the synthetic thiol-reactive lipopeptide adjuvant anchor Pam3CSS-Mal were reacted, at 25°C and pH 6.5, with equimolar quantities of the peptides ErbB2 (p63-71), derivatized with a CG linker at its N-terminus, and HA307-319, derivatized with a C-linker at its C-terminus. Abbreviations PC, phosphatidylcholine PE, phosphatidylethanolamine SUV, small unilamellar vesicles. Source From Refs. 11, 74.

The induction of CD4+ T helper 1 responses suggests that IRIV could provide adjuvance to the generation of HLA class I-restricted CTL responses. Thus, we addressed the capacity of IRIV to enhance the induction of CTL specific for influenza matrix (IM) 58-66 epitope and Melan-A/Mart-127-35 melanoma-associated epitope. Briefly, CD 14-cells isolated from healthy donor s peripheral blood were cocultured with autologous iDC in presence of peptide and empty IRIV or in presence of peptide alone. 

CTL induction experiments consistently demonstrate that IRIV indeed enhance induction of HLA class I-restricted CTL specific for IMsg-ee and Melan-A/Mart-127-35 epitopes. CTL induction in presence of irradiated or nonirradiated CD4+ cells showed that IRIV CTL adjuvance requires CD4+ T-cell activation. Remarkably, IRIV CTL adjuvance observed in our in vitro studies is solely due to IRIV immunogenicity and independent of peptide delivery and protection capacities, as peptides were not encapsulated in nor attached to IRIV. Further studies are warranted to clarify whether and to what extent delivery, protection, and immunogenic capacities of IRIV synergize in CTL adjuvance. The fact that IRIV adjuvance was observed in relation to the tumor-associated epitope Melan-A/Mart-127-35 encourages further evaluation of IRIV as potential adjuvants in cancer... 

Successful vaccines have several important properties such as safety, effectiveness, low cost per dose, and ease of preparation. Vaccines, whether peptide, protein, or DNA, have limited potency without codelivery with an adjuvant and/or a specialized delivery system (11). There is currently a lack of safe, nontoxic, effective. Food and Drug Administration (FDA)-approved vaccine adjuvants capable of stimulating cellular (Thl) immunity (12). Most potent immune activators are also toxic at relatively low doses and cannot, therefore, be successfully used as adjuvants (12). 

Recently, the activities of host defense peptides related to the resolution of infection have been suggested to result in part from nondirect antimicrobial activities. It has been postulated that immunomodulation may represent the primary action of these peptides in vivo as the immunomodulatory activities are retained under physiological conditions in contrast to the direct antimicrobial activities of most natural mammalian host defense peptides. These immunomodulatory activities include, but are not limited to, direct chemotactic activity, induction of chemokines and other immune mediators, stimulation of leukocyte degranulation and other microbicidal activities, effects on leukocyte and epithelial cell survival and apoptosis, stimulation of epithelial and endothelial cell proliferation, promotion of wound healing and angiogenesis, antiendotoxic and anti-inflammatory activities, and adjuvant fiinctions. These will be described in detail in the following sections and a summary is found in Table 1. 

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