Recombinant vector vaccines and within-host evolution

James Bull; Scott L. Nuismer; Rustom Antia

The self-limiting effect of anti-vaccine immunity depends heavily on the impairment parameter. The two 291 effects do not interact to make the problem worse than from their separate effects. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 is high). Second, the vaccine should elicit a large response to this antigen. This requires that the antigen 300 rapidly elicits immunity (i.e. has low φ X , and in terms of immunology it should be an immunogenic antigen), 301 and also requires a high vaccine viral load to generate a large response. Engineering this requires tackling 302 a trade-off between avoiding vaccine clearance (i.e. having a low k X ) but allowing for rapid clearance of 303 the pathogen (having a high k P ). Vaccines designed to express the antigen in a form that is different from 304 that in the pathogen might help solve this problem. Thus, to elicit immunity to influenza, one might design 305 secreted forms of the hemagglutinin or neuraminidase proteins. A recombinant hemagglutinin protein that is 306 secreted rather than on the virion surface would prevent the antibody response to this protein from clearing 307 the recombinant vector vaccine (have low k X ) without compromising the clearance of the influenza virus 308 pathogen which has hemagglutinin on its surface (i.e. has high k P ). In this manner our model allows the 309 identification and tuning of parameters that affect vaccine efficacy, and a comprehensive search of parameter 310 space would identify ideal combinations of vaccine properties. We now turn to vaccine designs that overcome 311 problems created by evolution, our specific interest here.