Tailoring the Immune Response via Customization of Pathogen Gene Expression

Figure 1

Induction of a “just right” immune response, as explained with regard to the damage-response framework (DRF). This curve, based on the DRF of how a host responds to virulence factors and pathogens, was first put forth by Pirofski and Casadevall [8, 9]. The DRF hypothesizes that human disease resulting from microbial infection manifests in two ways: (1) there is a response that is too robust (wild type), which is deleterious to the host or (2) a response that is insufficient, allowing unchecked invasion and succumbing to infection. Also, the low immune response portion of the curve can be viewed with regard to knockout strains with low efficacy as vaccines. Synthetic strains would be in the minimum of the DRF because they are expressing low levels of the toxin, allowing for an increased immune response as compared to the knockout, but below the disease threshold.