scholarly journals Designing transmissible viral vaccines for evolutionary robustness and maximum efficiency

2021 ◽  
Author(s):  
Nathan Layman ◽  
Beth M Tuschhoff ◽  
Scott L Nuismer
Keyword(s):  
Evolutionary Dynamics ◽  
Emerging Infectious Diseases ◽  
Human Infection ◽  
Maximum Efficiency ◽  
Trade Offs ◽  
Animal Pathogens ◽  
Hard To Reach Populations ◽  
Evolutionary Robustness ◽  
Overall Performance ◽  
Viral Vaccines

Abstract The danger posed by emerging infectious diseases necessitates the development of new tools that can mitigate the risk of animal pathogens spilling over into the human population. One promising approach is the development of recombinant viral vaccines that are transmissible, and thus capable of self-dissemination through hard to reach populations of wild animals. Indeed, mathematical models demonstrate that transmissible vaccines can greatly reduce the effort required to control the spread of zoonotic pathogens in their animal reservoirs, thereby limiting the chances of human infection. A key challenge facing these new vaccines, however, is the inevitability of evolutionary change resulting from their ability to self-replicate and generate extended chains of transmission. Further, carrying immunogenic transgenes is often costly, either in terms of metabolic burden, increased competition with the pathogen, or due to unintended interactions with the viral host regulatory network. As a result, natural selection is expected to favor vaccine strains that down-regulate or delete these transgenes resulting in increased rates of transmission and reduced efficacy against the target pathogen. In addition, efficacy and evolutionary stability will often be at odds; as when longer, more efficacious antigens experience faster rates of evolutionary decay. Here we ask how such trade-offs influence the overall performance of transmissible vaccines. We find that evolutionary instability can substantially reduce performance, even for vaccine candidates with the ideal combination of efficacy and transmission. However, we find that, at least in some cases, vaccine stability and overall performance can be improved by the inclusion of a second, redundant antigen. Overall, our results suggest that the successful application of recombinant transmissible vaccines will require consideration of evolutionary dynamics and epistatic effects, as well as basic measurements of epidemiological features.

Biosecurity and Public Health Ethics Issues Raised by Biological Threats

2019 ◽  
pp. 773-785
Author(s):  
Nicholas Evans ◽  
Thomas Inglesby
Keyword(s):  
Public Health ◽  
Resource Allocation ◽  
Infectious Diseases ◽  
Ethical Issues ◽  
Emerging Infectious Diseases ◽  
Biological Weapon ◽  
Ethical Values ◽  
Dual Use ◽  
Health Concerns ◽  
Trade Offs

This chapter introduces ethical issues that arise in the context of biosecurity: policies and actions intended to prevent the development or emergence, or mitigate the consequences, of serious biological threats. These threats could include deliberate biological weapon attacks (bioterrorism), pandemics, emerging infectious diseases, or major laboratory accidents. The basic values that underpin these public health concerns are first introduced. Ethical issues that arise before, during, and following a biosecurity crisis are then examined, including issues of resource allocation, dual-use research, and the possibility of quarantine. Their resolution requires trade-offs among different ethical values, including utility, fairness, and liberty.

scholarly journals Performance of Five Commercial Identification Platforms for Identification of Staphylococcus delphini

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Matthew C. Canver ◽  
Tsigereda Tekle ◽  
Samantha T. Compton ◽  
Katrina Callan ◽  
Eileen M. Burd ◽  
...  
Keyword(s):  
Distinct Species ◽  
Human Infection ◽  
Species Level ◽  
Accurate Identification ◽  
Content Type ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Staphylococcus Intermedius ◽  
Animal Pathogens ◽  
Tof Ms

ABSTRACT The Staphylococcus intermedius group (SIG) is a collection of coagulase-positive staphylococci consisting of four distinct species, namely, Staphylococcus cornubiensis, Staphylococcus delphini, Staphylococcus intermedius, and Staphylococcus pseudintermedius. SIG members are animal pathogens and rare causes of human infection. Accurate identification of S. pseudintermedius has important implications for interpretation of antimicrobial susceptibility testing data and may be important for other members of the group. Therefore, we sought to evaluate the performance of five commercially available identification platforms with 21 S. delphini isolates obtained from a variety of animal and geographic sources. Here, we show that automated biochemical platforms were unable to identify S. delphini to the species level, a function of its omission from their databases, but could identify isolates to the SIG level with various degrees of success. However, all automated systems misidentified at least one isolate as Staphylococcus aureus. One matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) system was able to identify S. delphini to the species level, suggesting that MALDI-TOF MS is the best option for distinguishing members of the SIG. With the exception of S. pseudintermedius, it is unclear if other SIG members should be routinely identified to the species level; however, as our understanding of their role in animal and human diseases increases, it may be necessary and important to do so.

scholarly journals Cucumber mosaic virus satellite RNAs that induce similar symptoms in melon plants show large differences in fitness

2011 ◽  
Vol 92 (8) ◽  
pp. 1930-1938 ◽  
Author(s):  
Mónica Betancourt ◽  
Aurora Fraile ◽  
Fernando García-Arenal
Keyword(s):  
Cucumber Mosaic Virus ◽  
Mosaic Virus ◽  
Evolutionary Dynamics ◽  
Plant Biomass ◽  
Aphid Transmission ◽  
Helper Virus ◽  
Relative Fitness ◽  
Single Infection ◽  
Trade Offs ◽  
Satellite Rnas

Two groups of Cucumber mosaic virus (CMV) satellite RNAs (satRNAs), necrogenic and non-necrogenic, can be differentiated according to the symptoms they cause in tomato plants, a host in which they also differ in fitness. In most other CMV hosts these CMV-satRNA cause similar symptoms. Here, we analyse whether they differ in traits determining their relative fitness in melon plants, in which the two groups of CMV-satRNAs cause similar symptoms. For this, ten necrogenic and ten non-necrogenic field satRNA genotypes were assayed with Fny-CMV as a helper virus. Neither type of CMV-satRNA modified Fny-CMV symptoms, and both types increased Fny-CMV virulence similarly, as measured by decreases in plant biomass and lifespan. Necrogenic and non-necrogenic satRNAs differed in their ability to multiply in melon tissues; necrogenic satRNAs accumulated to higher levels both in single infection and in competition with non-necrogenic satRNAs. Indeed, multiplication of some non-necrogenic satRNAs was undetectable. Transmission between hosts by aphids was less efficient for necrogenic satRNAs as a consequence of a more severe reduction of CMV accumulation in leaves. The effect of CMV accumulation on aphid transmission was not compensated for by differences in satRNA encapsidation efficiency or transmissibility to CMV progeny. Thus, necrogenic and non-necrogenic satRNAs differ in their relative fitness in melon, and trade-offs are apparent between the within-host and between-host components of satRNA fitness. Hence, CMV-satRNAs could have different evolutionary dynamics in CMV host-plant species in which they do not differ in pathogenicity.

scholarly journals Trade-offs between individual and ensemble forecasts of an emerging infectious disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rachel J. Oidtman ◽  
Elisa Omodei ◽  
Moritz U. G. Kraemer ◽  
Carlos A. Castañeda-Orjuela ◽  
Erica Cruz-Rivera ◽  
...  
Keyword(s):  
Human Mobility ◽  
Emerging Infectious Diseases ◽  
Spatiotemporal Variation ◽  
Emerging Pathogens ◽  
Ensemble Forecasts ◽  
Transmission Potential ◽  
Trade Offs ◽  
Probabilistic Forecasts ◽  
Model Structures ◽  
Answering Questions

AbstractProbabilistic forecasts play an indispensable role in answering questions about the spread of newly emerged pathogens. However, uncertainties about the epidemiology of emerging pathogens can make it difficult to choose among alternative model structures and assumptions. To assess the potential for uncertainties about emerging pathogens to affect forecasts of their spread, we evaluated the performance 16 forecasting models in the context of the 2015-2016 Zika epidemic in Colombia. Each model featured a different combination of assumptions about human mobility, spatiotemporal variation in transmission potential, and the number of virus introductions. We found that which model assumptions had the most ensemble weight changed through time. We additionally identified a trade-off whereby some individual models outperformed ensemble models early in the epidemic, but on average the ensembles outperformed all individual models. Our results suggest that multiple models spanning uncertainty across alternative assumptions are necessary to obtain robust forecasts for emerging infectious diseases.

scholarly journals Functional and evolutionary trade-offs co-occur between two consolidated memory phases in Drosophila melanogaster

2012 ◽  
Vol 279 (1744) ◽  
pp. 4015-4023 ◽  
Author(s):  
Fabrice Lagasse ◽  
Celine Moreno ◽  
Thomas Preat ◽  
Frederic Mery
Keyword(s):  
Evolutionary Dynamics ◽  
Functional Relationship ◽  
Learning Task ◽  
Long Term Memory ◽  
Phenotypic Traits ◽  
Trade Offs ◽  
Memory Phase ◽  
Fitness Benefits ◽  
Benefits And Costs

Memory is a complex and dynamic process that is composed of different phases. Its evolution under natural selection probably depends on a balance between fitness benefits and costs. In Drosophila , two separate forms of consolidated memory phases can be generated experimentally: anaesthesia-resistant memory (ARM) and long-term memory (LTM). In recent years, several studies have focused on the differences between these long-lasting memory types and have found that, at the functional level, ARM and LTM are antagonistic. How this functional relationship will affect their evolutionary dynamics remains unknown. We selected for flies with either improved ARM or improved LTM over several generations, and found that flies selected specifically for improvement of one consolidated memory phase show reduced performance in the other memory phase. We also found that improved LTM was linked to decreased longevity in male flies but not in females. Conversely, males with improved ARM had increased longevity. We found no correlation between either improved ARM or LTM and other phenotypic traits. This is, to our knowledge, the first evidence of a symmetrical evolutionary trade-off between two memory phases for the same learning task. Such trade-offs may have an important impact on the evolution of cognitive capacities. On a neural level, these results support the hypothesis that mechanisms underlying these forms of consolidated memory are, to some degree, antagonistic.

scholarly journals The Invasive Bank Vole (Myodes glareolus): A Model System for Studying Parasites and Ecoimmunology during a Biological Invasion

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2529
Author(s):  
Andrew McManus ◽  
Celia V. Holland ◽  
Heikki Henttonen ◽  
Peter Stuart
Keyword(s):  
Emerging Infectious Diseases ◽  
Model System ◽  
Helminth Species ◽  
Human Interaction ◽  
Myodes Glareolus ◽  
Enemy Release ◽  
Trade Offs ◽  
Primary Driver ◽  
Immunological Research ◽  
Wildlife Pathogens

The primary driver of the observed increase in emerging infectious diseases (EIDs) has been identified as human interaction with wildlife and this increase has emphasized knowledge gaps in wildlife pathogens dynamics. Wild rodent models have proven excellent for studying changes in parasite communities and have been a particular focus of eco-immunological research. Helminth species have been shown to be one of the factors regulating rodent abundance and indirectly affect disease burden through trade-offs between immune pathways. The Myodes glareolus invasion in Ireland is a unique model system to explore the invasion dynamics of helminth species. Studies of the invasive population of M. glareolus in Ireland have revealed a verifiable introduction point and its steady spread. Helminths studies of this invasion have identified enemy release, spillover, spillback and dilution taking place. Longitudinal studies have the potential to demonstrate the interplay between helminth parasite dynamics and both immune adaptation and coinfecting microparasites as M. glareolus become established across Ireland. Using the M. glareolus invasion as a model system and other similar wildlife systems, we can begin to fill the large gap in our knowledge surrounding the area of wildlife pathogen dynamics.

scholarly journals Exploiting evolutionary herding to control drug resistance in cancer

2019 ◽  
Author(s):  
Ahmet Acar ◽  
Daniel Nichol ◽  
Javier Fernandez-Mateos ◽  
George D. Cresswell ◽  
Iros Barozzi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Single Cell ◽  
Evolutionary Dynamics ◽  
Clonal Evolution ◽  
Genomic Analysis ◽  
Treatment Resistance ◽  
Control Treatment ◽  
Patient Specific ◽  
Control Drug ◽  
Trade Offs

AbstractDrug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased growth rate or increased sensitivity to another drug due to evolutionary trade-offs. This weakness can be exploited in the clinic using an approach called ‘evolutionary herding’ that aims at controlling the tumour cell population to delay or prevent resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here we present a novel approach for evolutionary herding based on a combination of single-cell barcoding, very large populations of 108–109cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary herding in non-small cell lung cancer, showing that herding allows shifting the clonal composition of a tumour in our favour, leading to collateral drug sensitivity and proliferative fitness costs. Through genomic analysis and single-cell sequencing, we were also able to determine the mechanisms that drive such evolved sensitivity. Our approach allows modelling evolutionary trade-offs experimentally to test patient-specific evolutionary herding strategies that can potentially be translated into the clinic to control treatment resistance.

scholarly journals Trade-offs between individual and ensemble forecasts of an emerging infectious disease

2021 ◽  
Author(s):  
Rachel J Oidtman ◽  
Elisa Omodei ◽  
Moritz U. G. Kraemer ◽  
Carlos A. Casteneda-Orjuela ◽  
Erica Cruz-Rivera ◽  
...  
Keyword(s):  
Human Mobility ◽  
Emerging Infectious Diseases ◽  
Transmission Model ◽  
Ensemble Model ◽  
Emerging Pathogens ◽  
Coupled Models ◽  
Forecast Performance ◽  
Transmission Potential ◽  
Trade Offs ◽  
Probabilistic Forecasts

When new pathogens emerge, numerous questions arise about their future spread, some of which can be addressed with probabilistic forecasts. The many uncertainties about the epidemiology of emerging pathogens can make it difficult to choose among model structures and assumptions, however. To assess the potential for uncertainties about emerging pathogens to affect forecasts of their spread, we evaluated the performance of a suite of 16 forecasting models in the context of the 2015-2016 Zika epidemic in Colombia. Each model featured a different combination of assumptions about the role of human mobility in driving transmission, spatiotemporal variation in transmission potential, and the number of times the virus was introduced. All models used the same core transmission model and the same iterative data assimilation algorithm to generate forecasts. By assessing forecast performance through time using logarithmic scoring with ensemble weighting, we found that which model assumptions had the most ensemble weight changed through time. In particular, spatially coupled models had higher ensemble weights in the early and late phases of the epidemic, whereas non-spatial models had higher ensemble weights at the peak of the epidemic. We compared forecast performance of the equally-weighted ensemble model to each individual model and identified a trade-off whereby certain individual models outperformed the ensemble model early in the epidemic but the ensemble model outperformed all individual models on average. On balance, our results suggest that suites of models that span uncertainty across alternative assumptions are necessary to obtain robust forecasts in the context of emerging infectious diseases.

A multifunction trade-off has contrasting effects on the evolution of form and function

2020 ◽  
Author(s):  
Katherine A Corn ◽  
Christopher M Martinez ◽  
Edward D Burress ◽  
Peter C Wainwright
Keyword(s):  
Evolutionary Dynamics ◽  
Functional Diversification ◽  
Form And Function ◽  
Kinematic Evolution ◽  
Rates Of Evolution ◽  
Trade Offs ◽  
Feeding Mechanics ◽  
And Function ◽  
Suction Performance ◽  
Clear Support

Abstract Trade-offs caused by the use of an anatomical apparatus for more than one function are thought to be an important constraint on evolution. However, whether multifunctionality suppresses diversification of biomechanical systems is challenged by recent literature showing that traits more closely tied to trade-offs evolve more rapidly. We contrast the evolutionary dynamics of feeding mechanics and morphology between fishes that exclusively capture prey with suction and multifunctional species that augment this mechanism with biting behaviors to remove attached benthic prey. Diversification of feeding kinematic traits was, on average, over 13.5 times faster in suction feeders, consistent with constraint on biters due to mechanical trade-offs between biting and suction performance. Surprisingly, we found that the evolution of morphology contrasts directly with these differences in kinematic evolution, with significantly faster rates of evolution of head shape in biters. This system provides clear support for an often postulated, but rarely confirmed prediction that multifunctionality stifles functional diversification, while also illustrating the sometimes weak relationship between form and function.

scholarly journals Identification of Optimal Process Parameter Settings Based on Manufacturing Performance for Fused Filament Fabrication of CFR-PEEK

2020 ◽  
Vol 10 (13) ◽  
pp. 4630
Author(s):  
Kijung Park ◽  
Gayeon Kim ◽  
Heena No ◽  
Hyun Woo Jeon ◽  
Gül E. Okudan Kremer
Keyword(s):  
Layer Thickness ◽  
Optimal Parameter ◽  
Lower Layer ◽  
Critical Role ◽  
Performance Measure ◽  
Fused Filament Fabrication ◽  
Trade Offs ◽  
Manufacturing Performance ◽  
Overall Performance ◽  
The Impact

Fused filament fabrication (FFF) has been proven to be an effective additive manufacturing technique for carbon fiber reinforced polyether–ether–ketone (CFR-PEEK) due to its practicality in use. However, the relationships between the process parameters and their trade-offs in manufacturing performance have not been extensively studied for CFR-PEEK although they are essential to identify the optimal parameter settings. This study therefore investigates the impact of critical FFF parameters (i.e., layer thickness, build orientation, and printing speed) on the manufacturing performance (i.e., printing time, dimensional accuracy, and material cost) of CFR-PEEK outputs. A full factorial design of the experiments is performed for each of the three sample designs to identify the optimal parameter combinations for each performance measure. In addition, multiple response optimization was used to derive optimal parameter settings for the overall performance. The results show that the optimal parameter settings depend on the performance measures regardless of the designs, and that the layer thickness plays a critical role in the performance trade-offs. In addition, lower layer thickness, horizontal orientation, and higher speed form the optimal settings to maximize the overall performance. The findings from this study indicate that FFF parameter settings for CFR-PEEK should be identified through multi-objective decision making that involves conflicts between the operational objectives for the parameter settings.

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