Vaccines, synthetic

Other types of branched peptide dendrimers, known as multiple antigen peptides (MAPs), have been synthesized to mimic proteins for applications, for instance as synthetic vaccines, serodiagnostics, peptide inhibitors and intracellular delivery vehicles. Since this concept has been recently described in detail elsewhere [11], only the conceptual framework will be briefly presented here. Tam and coworkers have developed a dendritic core based on lysine units for the construction of MAPs [12-15] (Fig. 3). Carrying antigens at their periphery these MAPs have been designed to increase antigenicity and immunogenicity of peptides. 

The development of vaccines is one of the most successful practical applications in immunology and in this field it is currently fashionable to make the reductionist claim that it will soon be possible to design effective synthetic vaccines on the basis of our knowledge of the molecules involved in immunological interactions. It seems to me that this claim arises from an unwarranted faith in the power of a reductionist approach for solving complex biological problems. Such a claim does not take into account that the protection against disease that can be achieved by vaccination is a... 

In the rare case when a peptide showing some promise has been identified, further immunization trials are necessary to establish its value as a practical synthetic vaccine. Since peptides are usually poor immunogens and do not mimic well the conformation of the corresponding antigenic site in the... 

Arnon, R. (1987), Synthetic Vaccines, Vols 1 and 2, CRC Press, Boca Raton, FL. 

Nicholson, B. H. (1994), Synthetic Vaccines, Blackwell Scientific Publishers, Oxford, UK, p. 542. 

Koganty, R.R., Reddish, M.A., and Fongenecker, B.M. (1996) Glycopeptide- and carbohydrate-based synthetic vaccines for the immunotherapy of cancer. Drug Disco. Today, 1, 190-198. 

Similar synthetic vaccines have also been constructed that confer immunological protection against bacterial toxins, including diphtheria and cholera toxins. Although coupling to a carrier is... 

Engineered antigen Partly or totally synthetic ag + rDNA production Probably predictable Rigorous Synthetic vaccine for polio myelitis or hepatitis B... 

Coupling of Peptides to the Surface of Liposomes—Application to Liposome-Based Synthetic Vaccines... 

Similar synthetic vaccines have also been constructed which confer immunological protection against bacterial toxins, including diphtheria and cholera toxins. While coupling to a carrier is generally required to elicit an immunological response, some carriers are inappropriate due to their ability to elicit a hypersensitive reaction, particularly when repeat injections are undertaken. Such difficulties can be avoided by judicious choice of carrier. Often a carrier normally used for vaccination is itself used, e.g. tetanus toxoid has been used as a carrier for peptides derived from influenza haemagglutinin and Plasmodium falciparum. 

Figure 13.12 A synthetic vaccine bearing multiple carbohydrate antigens KLH, keyhole limpet hemocyanin.

Keding S J, Danishefsky S J. Prospects for total S3mthesis a vision for a totaUy synthetic vaccine targeting epithelial tumors. Proc Natl Acad Sci 2004 101 11937-11942. 

Lomonossoff, G.P. and Johnson, G.E. (1996). Use of macromolecular assemblies as expression systems for peptides and synthetic vaccines. Curr. Opin. Struct. Biol. 6 176-182. 

Precise definition of the host-protection epitope(s) of the Taenia and Echinococcus vaccine antigens would be valuable if it were to lead to the development of a synthetic vaccine or provide reagents to assist with quality control of vaccine production. Identification of a limited number of host-protective fragments may allow the recombinant antigen to be replaced by synthetic peptides. This would have significant advantages in the production... 

Fig. 8. Synthetic vaccines against Haemophilus influenzae, protein = HSA or TT, n 7.

Jackson, D.C., Lau, Y.F., Le, T., et al. (2004) A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. Proc. Natl. Acad. Sci. USA 101(43), 15440-15445. 

Nardin, E.H., Calvo-Calle, J.M., Oliveira, G.A., et al. (1998) Plasmodium falciparum polyoximes highly immunogenic synthetic vaccines constructed by chemos-elective ligation of repeat B-cell epitopes and a universal T-cell epitope of CS protein. Vaccine 16(6), 590-600. 

Dietzschold, B., Gore, M., Marchandiar, D., et al. (1990) Structural and immunological characterization of a linear virus-neutralizing epitope of the rabies virus glycoprotein and its possible use in a synthetic vaccine. J. Virol. 64,... 

McGeary RP, Jablonkai I, Toth I (2002) Towards synthetic vaccines built on carbohydrate cores. Lett Pept Sci 8(3-5) 273-276... 

The formation of CC bonds to prepare glycoconjugates has also gained some attention. For example, Diels-Alder cycloaddition has allowed the preparation of synthetic glycoproteins [144] and the construction of a synthetic vaccine candidate against Neisseria meningitidis A [145], These methods relied on a pretagging step to create suitable protein reactants. 

Some key aspects have to be considered when designing such synthetic vaccines because the immunogenic activity of the conjugate depends on the nature of the hapten, the loading onto the protein, and the characteristics of the carrier. In... 

McGeary, R. P., Jablonkai, 1., and Toth, I. (2001) Carbohydrate-based templates for synthetic vaccines and drug delivery. Tetrahedron 57, 8733-8742. 

Bioconjugates play an important role in several fields of biomolecular and biomedicinal sciences. Protein/polypeptide-based conjugates with covalently attached epitope peptides are considered as potential synthetic vaccine candidates and/or target antigens in affinity-based bioassays (e.g., ELISA, BIACORE) (1,2). Drugs such as daunomycin, methotrexate, and a GnRH analog coupled either to monoclonal antibodies or to synthetic linear or branched polypeptides... 

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