Recombinant vector vaccine evolution
Fig 4
Representative dynamics contrasting vaccine evolution with no evolution.
The combination of intrinsic fitness effects and revertant abundance in the inoculum has the most profound effect in depressing immunity, but depressions are observed even when any evolution is allowed. The vertical axes use a log scale, thus diminish the visual appearance of changes. (Top left): Absence of revertant (i.e. no pre-host or within-host evolution). (Top right): The revertant is included at half the inoculum (representing pre-host evolution); it has no intrinsic fitness advantage over vaccine. Immunity (to vaccine) is reduced to just over a third of the level with no evolution. (Lower left): The revertant is a small fraction of the inoculum (0.01) but it has a 20% fitness advantage over vaccine. The level of immunity is 71% that with no evolution. (Lower right): The revertant is half the inoculum and has a 20% fitness advantage over vaccine. The level of immunity is now less than 0.3% that with no evolution—a depression of almost 3 orders of magnitude. The trials are parameterized so that virus is controlled by innate immunity with final clearance due to adaptive immunity; the mutation rate is 0 in all cases. Equations, initial conditions and parameter values not shown here are given in S1 Appendix; R code is included in S1 File.