Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously.

With the aim to improve the efficacy of therapeutic vaccinesthat target self-antigens, we have developed a novel fusion proteinvaccine on the basis of the C-terminal multimerizing end of the variable lymphocyte receptor B (VLRB), the Ig equivalent in jawless fishes. Recombinant vaccineswere produced in Escherichia coli by fusing the VLRB sequence to 4 different cancer-associated target molecules. The anti–self-immune response generated in mice that were vaccinated with VLRB vaccines was compared with the response in mice that received vaccines that contained bacterial thioredoxin(TRX), previously identified as an efficient carrier. The anti–self-Abs were analyzed with respect to titers, binding properties, and duration of response. VLRB-vaccinated mice displayed a 2- to 10-fold increase in anti–self-Ab titers and a substantial decrease in Abs against the foreign part of the fusion proteincompared with the response in TRX-vaccinated mice (P < 0.01). VLRB-generated Ab response had duration similar to t...