A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses

摘要

A simple generic peptide-based vaccine structure that targets Toll-like receptor 2-expressing dendritic cells and causes their activation is described. The vaccines are totally synthetic, serve as their own adjuvant, and are composed of (i) a single helper T cell epitope, (ii) a target epitope that is either recognized by CD8+ T cells or B cells, and (iii) a Toll-like receptor 2-targeting lipid moiety, S-[2,3-bis(palmitoyloxy)propyl]cysteine, that is situated between the peptide epitopes to form a branched configuration. The different CD8+ T cell epitopes examined were from (i) influenza virus, (ii) the intracellular bacterium Listeria monocytogenes, and (iii) ovalbumin as a model tumor antigen. Vaccines containing a B cell epitope from gastrin or luteinizing hormone-releasing hormone as a B cell epitope were also examined for their ability to elicit antibody against the parent hormones. Each of the vaccines was capable of inducing either CD8+ T cell or antibody-mediated immune responses. The lipidated vaccines, but not the nonlipidated vaccines, were able to mediate protection against viral or bacterial infection and mediate prophylactic and therapeutic anticancer activity. The two hormone-based vaccines induced high antibody titers, which in the case of luteinizing hormone-releasing hormone resulted in abrogation of reproductive function. These results highlight the utility of simple, totally synthetic, epitope-based vaccines.