Three in One

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Science  12 Nov 2004:
Vol. 306, Issue 5699, pp. 1103
DOI: 10.1126/science.306.5699.1103d

Vaccines are designed to generate robust immunity through the coactivation of the adaptive and innate arms of the immune system. This is achieved by steering tripartite responses to antigenic epitopes by helper T (TH) cells, antigen-presenting dendritic cells (DCs), and antibody-producing B cells or the cytotoxic lymphocytes (CTLs) that ultimately execute pathogen clearance. However, the poor inherent immunogenicity of peptide epitopes favored in some vaccine formulas dictates the need for including complex and potentially toxic adjuvants that stimulate the essential priming activity of DCs.

Jackson et al. have refined this approach by synthesizing structures containing TH epitopes coupled to B cell or CTL target epitopes. These were linked via a lipid moiety, which served to activate DCs through binding and activation of the innate signaling receptor TLR2. With different epitope combinations, strong antibody and CTL responses could be elicited in models of viral and bacterial infection, as well as to tumors, and were comparable to responses to an adjuvant traditionally used in vaccines. The ability to combine adjuvant and antigenic properties in a single synthetic formula offers an attractive approach for future vaccine design. — SJS

Proc. Natl. Acad. Sci. U.S.A. 101, 15440 (2004).

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