Synthetic bacterial lipopeptide analogs: structural requirements for adjuvanticity

Modern vaccines aim at conferring immune protection, independently of the nature of the etiological agent causing the disease. These new therapeutics are based on highly purified antigenic moieties that offer potential advantages over traditional vaccines, including a high degree of safety and the capacity of eliciting highly specific immune responses. In spite of these advantages however, subunit vaccines tend to be poorly immunogenic in vivo, and require the coadministration of adjuvants that indirectly enhance cellular immunity. Thus, recombinant vaccines development is dependent on the design of new molecules, non-immunogenic per se, but endowed with immune modulatory properties. Synthetic analogs of bacterial lipoproteins were described more than a decade ago, but their capacity to act as adjuvants has been only recently dissected. These low molecular weight non-immunogenic molecules can be reproducibly synthetized, are safe, and of easy handling and administration. Furthermore, new experimental data from our laboratory reveal their powerful adjuvant effect on human HLA-I/II restricted T cell responses and identify the molecular and cellular requirements for optimal adjuvanticity.