Multistrain Models of Recombinant Transmissible Vaccines with Mutational Decay
Additional Funding Sources
This work was funded by NIH Grant No. R01GM122079 (S.L.N.).
Abstract
In the absence of gene flow, populations undergo local adaptation to their environment. Swamping occurs when migrant genes prevent local adaptation with high levels of gene flow. Although swamping is often depicted as a problem, it could be implemented to arrest unwanted evolution in GMOs which depend on the integrity of transgenes. In GMO vaccines, the fitness cost of carrying an antigen results in reversion to virulence or antigenic decay through a series of mutational steps. Zoonotic diseases pose an increasing threat to people, causing an estimated 2.7 million worldwide human deaths each year. Recombinant transmissible vaccines (RTVs) provide a way to reduce the risk of infectious diseases, especially zoonotic diseases with wildlife reservoirs that cannot be directly vaccinated. A well-documented two-strain SIR model, including pathogen and RTV, represents the situation where an RTV can mutate to its vector in one step. We built an n-strain model expanding upon this model by imagining a similar situation where the RTV must undergo n-1 mutations, rather than one, to revert to the vector. Although the vector is benign, it competes with the RTV for susceptible individuals, thereby reducing the benefits of the RTV. We found that the level of direct vaccination necessary depends on mutation rate and the decline in efficacy from each mutational step. This model allows us to quantify the amount of swamping in order to protect populations against infectious disease and prevent local adaptation.
Multistrain Models of Recombinant Transmissible Vaccines with Mutational Decay
In the absence of gene flow, populations undergo local adaptation to their environment. Swamping occurs when migrant genes prevent local adaptation with high levels of gene flow. Although swamping is often depicted as a problem, it could be implemented to arrest unwanted evolution in GMOs which depend on the integrity of transgenes. In GMO vaccines, the fitness cost of carrying an antigen results in reversion to virulence or antigenic decay through a series of mutational steps. Zoonotic diseases pose an increasing threat to people, causing an estimated 2.7 million worldwide human deaths each year. Recombinant transmissible vaccines (RTVs) provide a way to reduce the risk of infectious diseases, especially zoonotic diseases with wildlife reservoirs that cannot be directly vaccinated. A well-documented two-strain SIR model, including pathogen and RTV, represents the situation where an RTV can mutate to its vector in one step. We built an n-strain model expanding upon this model by imagining a similar situation where the RTV must undergo n-1 mutations, rather than one, to revert to the vector. Although the vector is benign, it competes with the RTV for susceptible individuals, thereby reducing the benefits of the RTV. We found that the level of direct vaccination necessary depends on mutation rate and the decline in efficacy from each mutational step. This model allows us to quantify the amount of swamping in order to protect populations against infectious disease and prevent local adaptation.
Comments
W80