QS-21 synergizes with recombinant interleukin-12 to create a potent adjuvant formulation for the fusion protein of respiratory syncytial virus

In the murine model of respiratory syncytial virus (RSV) infection, recombinant interleukin-12 (rIL-12) was previously demonstrated to be most effective as an adjuvant for fusion (F) protein-based vaccines after adsorption to alum adjuvant. Alum, however, is a potent inducer of polarized T-cell responses and the type 2 phenotype. In addition, studies in human cancer patients demonstrated that rIL-12 was toxic when administered systemically at high doses. Because of these issues, we investigated whether the saponin QS-21 could facilitate a reduction in dose of rIL-12 when F protein was prepared in the absence of alum (F/rIL-12). The results demonstrated that a suboptimal dose (0.8 mug) of QS-21 enhanced the capacity of F/rIL-2 to elicit antigen-dependent killer cell precursors and complement-assisted neutralizing antibodies in spleens and sera respectively of BALB/c mice. The killer cell activity of mice vaccinated with F/rIL-12 (0.1 mug) plus 0.8 mug QS-21 was equivalent to that elicited after vaccination by experimental infection, or with an optimal dose of QS-21. The neutralizing titers generated by F/rIL-12 (0.01 to 1.0 mug) were also significantly elevated in the presence of 0.8 mug QS-21. Thus, rIL-12 and QS-21 together form a potent adjuvant for eliciting functional cell-mediated and humoral immune responses against F protein.