Recombinant vector vaccines and within-host evolution

James Bull; Scott L. Nuismer; Rustom Antia

One major outcome of our analysis was that intuition about vaccine evolution was not easily translated into 367 18 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/545087 doi: bioRxiv preprint intuition about immunity. Indeed, even intuition about evolution often failed because that intuition was based 368 on vaccine versus revertant fitness, but the vaccine growth phase was short enough that differential fitness 369 had little effect on evolution. Even more fundamentally, intuition sometimes failed because the development 370 of immunity to vaccine could be unaffected by the revertant. Thus, our intuition suggested that vaccine 371 inferiority could stem from both an intrinsic fitness disadvantage and a disadvantage due to adaptive immunity 372 to the transgene/antigen. Both effects were found to impair the development of immunity to vaccine, but not 373 necessarily for the reasons suggested by our intuition. of whether vaccine evolution would lead to reduced antigen levels in vivo, but it would be less sensitive in 386 measuring evolution than is measuring mutation frequencies.