Figure 1.
Push-pull approach to optimizing vaccine efficacy for induction of T cell immunity. The basic skeleton of a vaccine is an antigen used to induce an immune response. We can improve on this at each of several steps as described in the text. First, we can improve the immunogenicity of the T-cell epitopes by substituting amino acids that interact with the MHC molecule to increase affinity, without altering the 3-dimensional configuration seen by the TCR. We call this epitope enhancement. Next, we can push the response with cytokines, costimulatory molecules and TLR ligands as molecular adjuvants, not only to increase the magnitude of the response, but also to improve the quality of the response. Even this is not sufficient because of the negative regulatory cells, surface molecules and cytokines that are often present and inhibit the immune response, so we need to overcome those to finally optimize the response (the “pull” of the approach). The examples shown are ones described in the text, but are not intended to be an exhaustive list. We call the overall strategy a “push-pull” approach. Modified from 96 with permission.