Biology subjects

Nuismer, S.

Publications and source records attributed to Nuismer, S..

3 recordsLinked to original sources

bioRxiv2022

Optimizing the delivery of self-disseminating vaccines in fluctuating wildlife popualtions

1Zoonotic pathogens spread by wildlife continue to spill into human populations and threaten human lives. A potential way to reduce this threat is by vaccinating wildlife species that harbor pathogens that are infectious to humans. Unfortunately, even in cases where vaccines can be distributed en masse as edible baits, achieving levels of vaccine coverage sufficient for pathogen elimination is rare. Developing vaccines that self-disseminate may help solve this problem by magnifying the impact of limited direct vaccination. Although models exist that quantify how well these self-disseminating vaccines will work when introduced into temporally stable wildlife populations, how well they will perform when introduced into populations with pronounced seasonal population dynamics remains unknown. Here we develop and analyze mathematical models of fluctuating wildlife populations that allow us to study how reservoir ecology, vaccine design, and vaccine delivery interact to influence vaccine coverage and opportunities for pathogen elimination. Our results demonstrate that the timing of vaccine delivery can make or break the success of vaccination programs. As a general rule, the effectiveness of self-disseminating vaccines is optimized by introducing after the peak of seasonal reproduction when the number of susceptible animals is near its maximum.

ecology↗

bioRxiv2020

A White Noise Approach to Evolutionary Ecology

Although the evolutionary response to random genetic drift is classically modelled as a sampling process for populations with fixed abundance, the abundances of populations in the wild fluctuate over time. Furthermore, since wild populations exhibit demographic stochasticity, it is reasonable to consider the evolutionary response to demographic stochasticity and its relation to random genetic drift. Here we close this gap in the context of quantitative genetics by deriving the dynamics of the distribution of a quantitative character and the abundance of a biological population from a stochastic partial differential equation driven by space-time white noise. In the process we develop a useful set of heuristics to operationalize the powerful, but abstract theory of white noise and measure-valued stochastic processes. This approach allows us to compute the full implications of demographic stochasticity on phenotypic distributions and abundances of populations. We demonstrate the utility of our approach by deriving a quantitative genetic model of diffuse coevolution mediated by exploitative competition for a continuum of resources. In addition to trait and abundance distributions, this model predicts interaction networks defined by rates of interactions, competition coefficients, or selection gradients. Analyzing the relationship between selection gradients and competition coefficients reveals independence between linear selection gradients and competition coefficients. In contrast, absolute values of linear selection gradients and quadratic selection gradients tend to be positively correlated with competition coefficients. That is, competing species that strongly affect each others abundance tend to also impose selection on one another, but the directionality is not predicted. This approach contributes to the development of a synthetic theory of evolutionary ecology by formalizing first principle derivations of stochastic models that underlie rigorous investigations of the relationship between feedbacks of biological processes and the patterns of diversity they produce.

ecology↗

bioRxiv2019

Recombinant vector vaccines and within-host evolution

Many recombinant vector vaccines are capable of replication within the host. They consist of a fully competent vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be intrinsically detrimental. Thus vaccine revertants that delete the transgene may evolve to dominate the within-host population and in doing so reduce the antigenicity of the vaccine. We apply mathematical and computational models to study this process, including the dynamics of vaccine and revertant growth plus the dynamics of innate and adaptive immunity. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that, despite possible fitness differences between vaccine and revertant, the opportunity for vaccine evolution is limited by the short period of growth before the viral population is cleared. Even less obvious, revertant per se does not interfere with immunity to vaccine except as the revertant suppresses vaccine abundance; the magnitude of this interference depends on mechanisms and timing of viral suppression. Adaptive immunity targeting the foreign antigen is also a possible basis of vaccine inferiority, but it is not worsened by vaccine evolution. Overall, we find that within-host vaccine evolution can sometimes matter to the adaptive immune response targeting the foreign antigen, but even when it does matter, simple principles of vaccine design and the control of inoculum composition can largely mitigate the effects. Author SummaryRecombinant vector vaccines are live replicating viruses that are engineered to carry extra genes derived from a pathogen - and these produce proteins against which we want to generate immunity. These genes may evolve to be lost during the course of replication within an individual, and there is a concern that this can severely limit the vaccines efficacy. The dynamics of this process are studied here with mathematical models. The potential for vaccine evolution is somewhat reduced by the short-term growth of the vaccine population before it is suppressed by the immune response. Even when within-host evolution can be a problem, the models show that increasing the vaccine inoculum size or ensuring that the inoculum is mostly pure vaccine can largely avoid the loss of immunity arising from evolution.

evolutionary biology↗