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Synthetic Vaccines: The Role of Adjuvants in Immune Targeting

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Abstract:

A clear understanding of the mechanism of function of immune stimulatory adjuvants, which commonly accompany vaccines, is beginning to emerge. Recent investigations have demonstrated that Toll-like receptors (TLRs) are the critical link between the innate and the adaptive immunity. This link, which is normally activated as a result of collaboration between adjuvants and TLRs in triggering adaptive immunity, has been a subject of several recent investigations. With the advent of well-defined synthetic small molecules, which are designed to either mimic the adjuvants or, as in many cases, to structurally represent pathogen associated molecular patterns, it is now possible to design reproducible experiments and to draw credible conclusions. An adjuvant alerts the host immune system through a mechanism similar to that of an infection by a pathogen, which involves interaction with a TLR followed by a ‘danger signal’ to the immune system. Secretion of cytokines and regulation of the expression of co-stimulatory molecules induced by innate response shape the magnitude and quality of adaptive response. Synthetic vaccines containing specific epitopes to which immune responses are desired, are expected to be far superior in target specificity while the benefits may be long-lasting. The immune responses by therapeutic vaccines are generally adaptive in nature and such responses often require the participation of the components of innate immunity, most importantly the TLRs and their pathogen-associated binding compliments. Structurally well-defined synthetic molecules derived from lipid A, muramyl di-peptide (MDP), and CpG motifs from bacterial DNA offer a wide range of immune stimulants for the development of fully synthetic vaccines. Lipo-peptide and self-adjuvanted antigens, in combination with additional immune stimulatory adjuvants in liposome delivery system, may be important in vaccine design. Combinations of synthetic mimics of microbial products are known to display synergistic effects in stimulating the immune system. Either alone or in combination with chemotherapy, innate immune therapy - using TLR ligands to stimulate the immune system - may offer an alternate therapeutic approach against rapidly mutating viral infections-(HIV / AIDS), and cancers.

Keywords: cytokine; innate immune therapy; innate immunity; self-adjuvanted synthetic antigen; synergistic effect; synthetic adjuvant; synthetic vaccine; toll-like receptor

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867033457340

Affiliations: Biomira Inc., 2011-94 Street, Edmonton, Alberta, T6N 1H1, Canada

Publication date: August 1, 2003

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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