Recombinant vector vaccine evolution
Fig 5
Viral load and the level of immunity to the vaccine antigen depend on evolution and vaccine composition (pre-host evolution).
The final vaccine load and immunity against the vaccine antigen depends heavily on two parameters, the inoculum composition (plotted on the x-axis as initial abundance of the revertant virus, W(0)) and the growth advantage of the revertant within the host (c, plotted on the y-axis). The heat maps show how, as the composition shifts toward revertant or as vector superiority increases (as we move to the right or up), there is a reduction in the viral load of the vaccine (defined as ∫ V dt, left panel) and in the magnitude of immunity to the vaccine antigen (X, right panel). The initial amount of vaccine virus is always V(0) = 1 (i.e. logV(0) = 0). Note that the graphs span high frequencies of revertant in the inoculum that should be easily avoided (log W(0) = 1, i.e. W(0) = 10 V(0))—if the researcher is alert to the possibility. We include such extremes merely to show that the outcome is relatively insensitive to small changes in vaccine composition. Equations, initial conditions and parameter values not shown here are given in S1 Appendix; R code is included in S1 File.