Workshop report: Optimization of animal models to better predict influenza vaccine efficacy.

Animal models that can recapitulate the human immune system are essential for the preclinical development of safe and efficacious vaccines. Development and optimization of representative animal models are key components of the NIAID strategic plan for the development of a universal influenza vaccine. To gain insight into the current landscape of animal model usage in influenza vaccine development, NIAID convened a workshop in Rockville, Maryland that brought together experts from academia, industry and government. Panelists discussed the benefits and limitations of the field's most widely-used animal models, identified currently available and critically needed resources and reagents, and suggested areas for improvement based on inadequacies of existing models. Although appropriately-selected animal models can be useful for evaluating safety, mechanism-of-action, and superiority over existing vaccines, workshop participants concluded that multiple animal models will likely be required to sufficiently test all aspects of a novel vaccine candidate. Refinements are necessary for all current model systems, for example, to better represent special human populations, and will be facilitated by the development and broader availability of new reagents. NIAID continues to support progress towards increasing the predictive value of animal models.

Phylogeography of rubella virus in Asia: Vaccination and demography shape synchronous outbreaks.

Rubella virus causes mild disease in children but for women in the early stages of pregnancy, it can cause spontaneous abortion, congenital rubella syndrome (CRS) and associated birth defects. Despite the availability of an effective vaccine, rubella virus continues to circulate endemically in several regions of the world. This is particularly true in East and Southeast (E/SE) Asia, where control efforts vary widely among countries that are well connected through travel and immigration. It is therefore important to understand how the regional persistence of rubella is affected both by dynamics occurring across countries and susceptibility within countries. Here, we use genetic and epidemiological data from countries in E/SE Asia to explore the phylogeography of rubella virus in this region. Our results underline that metapopulation dynamics are key for rubella persistence and highlight the source-sink population structure of the region. We identify countries that contribute to the regional metapopulation network and link epidemic dynamics to susceptibility profiles within each country. Our results indicate that human movement plays an important role in driving epidemic dynamics in E/SE Asia.

Small genome of the fungus Escovopsis weberi, a specialized disease agent of ant agriculture.

Many microorganisms with specialized lifestyles have reduced genomes. This is best understood in beneficial bacterial symbioses, where partner fidelity facilitates loss of genes necessary for living independently. Specialized microbial pathogens may also exhibit gene loss relative to generalists. Here, we demonstrate that Escovopsis weberi, a fungal parasite of the crops of fungus-growing ants, has a reduced genome in terms of both size and gene content relative to closely related but less specialized fungi. Although primary metabolism genes have been retained, the E. weberi genome is depleted in carbohydrate active enzymes, which is consistent with reliance on a host with these functions. E. weberi has also lost genes considered necessary for sexual reproduction. Contrasting these losses, the genome encodes unique secondary metabolite biosynthesis clusters, some of which include genes that exhibit up-regulated expression during host attack. Thus, the specialized nature of the interaction between Escovopsis and ant agriculture is reflected in the parasite's genome.

INTEGRATING PARASITES AND PATHOGENS INTO THE STUDY OF GEOGRAPHIC RANGE LIMITS.

The geographic distributions of all species are limited, and the determining factors that set these limits are of fundamental importance to the fields of ecology and evolutionary biology. Plant and animal ranges have been of primary concern, while those of parasites, which represent much of the Earth's biodiversity, have been neglected. Here, we review the determinants of the geographic ranges of parasites and pathogens, and explore how parasites provide novel systems with which to investigate the ecological and evolutionary processes governing host/parasite spatial distributions. Although there is significant overlap in the causative factors that determine range borders of parasites and free-living species, parasite distributions are additionally constrained by the geographic range and ecology of the host species' population, as well as by evolutionary factors that promote host-parasite coevolution. Recently, parasites have been used to infer population demographic and ecological information about their host organisms and we conclude that this strategy can be further exploited to understand geographic range limitations of both host and parasite populations.

The Role of Human Transportation Networks in Mediating the Genetic Structure of Seasonal Influenza in the United States.

Recent studies have demonstrated the importance of accounting for human mobility networks when modeling epidemics in order to accurately predict spatial dynamics. However, little is known about the impact these movement networks have on the genetic structure of pathogen populations and whether these effects are scale-dependent. We investigated how human movement along the aviation and commuter networks contributed to intra-seasonal genetic structure of influenza A epidemics in the continental United States using spatially-referenced hemagglutinin nucleotide sequences collected from 2003-2013 for both the H3N2 and H1N1 subtypes. Comparative analysis of these transportation networks revealed that the commuter network is highly spatially-organized and more heavily traveled than the aviation network, which instead is characterized by high connectivity between all state pairs. We found that genetic distance between sequences often correlated with distance based on interstate commuter network connectivity for the H1N1 subtype, and that this correlation was not as prevalent when geographic distance or aviation network connectivity distance was assessed against genetic distance. However, these patterns were not as apparent for the H3N2 subtype at the scale of the continental United States. Finally, although sequences were spatially referenced at the level of the US state of collection, a community analysis based on county to county commuter connections revealed that commuting communities did not consistently align with state geographic boundaries, emphasizing the need for the greater availability of more specific sequence location data. Our results highlight the importance of utilizing host movement data in characterizing the underlying genetic structure of pathogen populations and demonstrate a need for a greater understanding of the differential effects of host movement networks on pathogen transmission at various spatial scales.