Directed attenuation to enhance vaccine immunity
Fig 5
Heat maps for the log10 fold changes in pathology (top row) and immunity (bottom row) for changes in two parameters.
The effect of changing a single parameter alone is seen by moving parallel to the respective axis. The goal of attenuation is to reduce pathology from wild-type values (increase the level of blue, top row) and to increase immunity (increase redness, bottom row). Values of wild-type virus are given in upper right of each panel, values of the prospective vaccine in lower left. The goal is to have pathology become increasingly blue and immunity become increasingly red in traversing from wild-type to vaccine. The conventional attenuation strategy arising from reductions in the parameter r is seen to reduce both pathology and immunity (moving left along the horizontal axis in any of the left four panels). However, combining reductions in r with increasing the sensitivity of the adaptive immune response (i.e. decreasing ϕZ) or increasing the duration of innate immunity (i.e. increasing dZ) restores the level of immunity generated by the vaccine to that induced by the wild-type virus while reducing pathology (left two columns). The right column shows attenuation achieved by changes in a pair of parameters that does not include r.