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Transient disease dynamics across ecological scales

Analyses of transient dynamics are critical to understanding infectious disease transmission and persistence. Identifying and predicting transients across scales, from within-host to community-level patterns, plays an important role in combating ongoing epidemics and mitigating the risk of future outbreaks. Moreover, greater emphases on non-asymptotic processes will enable timely evaluations of wildlife and human diseases and lead to improved surveillance efforts, preventive responses, and intervention strategies. Here, we explore the contributions of transient analyses in recent models spanning the fields of epidemiology, movement ecology, and parasitology. In addition to their roles in predicting epidemic patterns and endemic outbreaks, we explore transients in the contexts of pathogen transmission, resistance, and avoidance at various scales of the ecological hierarchy. Examples illustrate how (i) transient movement dynamics at the individual host level can modify opportunities for transmission events over time; (ii) within-host energetic processes often lead to transient dynamics in immunity, pathogen load, and transmission potential; (iii) transient connectivity between discrete populations in response to environmental factors and outbreak dynamics can affect disease spread across spatial networks; and (iv) increasing species richness in a community can provide transient protection to individuals against infection. Ultimately, we suggest that transient analyses offer deeper insights and raise new, interdisciplinary questions for disease research, consequently broadening the applications of dynamical models for outbreak preparedness and management.

Theoretical Ecology↗

Diversity, origins and virulence of Avipoxviruses in Hawaiian Forest Birds

We cultured avian pox (Avipoxvirus spp.) from lesions collected on Hawai'i, Maui, Moloka'i, and 'Oahu in the Hawaiian Islands from 15 native or non-native birds representing three avian orders. Phylogenetic analysis of a 538 bp fragment of the gene encoding the virus 4b core polypeptide revealed two distinct variant clusters, with sequences from chickens (fowlpox) forming a third distinct basal cluster. Pox isolates from one of these two clusters appear closely related to canarypox and other passerine pox viruses, while the second appears more specific to Hawai'i. There was no evidence that birds were infected simultaneously with multiple pox virus variants based on evaluation of multiples clones from four individuals. No obvious temporal or geographic associations were observed and strict host specificity was not apparent among the 4b-defined field isolates. We amplified a 116 bp 4b core protein gene fragment from an 'Elepaio (Chasiempis sandwichensis) collected in 1900 on Hawai'i Island that clustered closely with the second of the two variants, suggesting that this variant has been in Hawai'i for at least 100 years. The high variation detected between the three 4b clusters provides evidence for multiple, likely independent introductions, and does not support the hypothesis of infection of native species through introduction of infected fowl. Preliminary experimental infections in native Hawai'i 'Amakihi (Hemignathus virens) suggest that the 4b-defined variants may be biologically distinct, with one variant appearing more virulent. These pox viruses may interact with avian malaria (Plasmodium relictum), another introduced pathogen in Hawaiian forest bird populations, through modulation of host immune responses. ?? 2007 Springer Science+Business Media B.V.

Conservation Genetics↗

Avian influenza shedding patterns in waterfowl: implications for surveillance, environmental transmission, and disease spread

Despite the recognized importance of fecal/oral transmission of low pathogenic avian influenza (LPAI) via contaminated wetlands, little is known about the length, quantity, or route of AI virus shed by wild waterfowl. We used published laboratory challenge studies to evaluate the length and quantity of low pathogenic (LP) and highly pathogenic (HP) virus shed via oral and cloacal routes by AI-infected ducks and geese, and how these factors might influence AI epidemiology and virus detection. We used survival analysis to estimate the duration of infection (from virus inoculation to the last day virus was shed) and nonlinear models to evaluate temporal patterns in virus shedding. We found higher mean virus titer and longer median infectious period for LPAI-infected ducks (10–11.5 days in oral and cloacal swabs) than HPAI-infected ducks (5 days) and geese (7.5 days). Based on the median bird infectious dose, we found that environmental contamination is two times higher for LPAI- than HPAI-infectious ducks, which implies that susceptible birds may have a higher probability of infection during LPAI than HPAI outbreaks. Less environmental contamination during the course of infection and previously documented shorter environmental persistence for HPAI than LPAI suggest that the environment is a less favorable reservoir for HPAI. The longer infectious period, higher virus titers, and subclinical infections with LPAI viruses favor the spread of these viruses by migratory birds in comparison to HPAI. Given the lack of detection of HPAI viruses through worldwide surveillance, we suggest monitoring for AI should aim at improving our understanding of AI dynamics (in particular, the role of the environment and immunity) using long-term comprehensive live bird, serologic, and environmental sampling at targeted areas. Our findings on LPAI and HPAI shedding patterns over time provide essential information to parameterize environmental transmission and virus spread in predictive epizootiologic models of disease risks.

Journal of Wildlife Diseases↗

Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat ( Tadarida brasiliensis )

Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat ( Tadarida brasiliensis ), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA- luc , RCN- luc ) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN- luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 x 10 4 PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats.

Vaccine↗

Impact of molecular modifications on the Immunogenicity and efficacy of recombinant raccoon poxvirus-vectored rabies vaccine candidates in mice

Rabies is an ancient disease that is responsible for approximately 59,000 human deaths annually. Bats (Order Chiroptera ) are thought to be the original hosts of rabies virus (RABV) and currently account for most rabies cases in wildlife in the Americas. Vaccination is being used to manage rabies in other wildlife reservoirs like fox and raccoon, but no rabies vaccine is available for bats. We previously developed a recombinant raccoonpox virus (RCN) vaccine candidate expressing a mosaic glycoprotein (MoG) gene that protected mice and big brown bats when challenged with RABV. In this study, we developed two new recombinant RCN candidates expressing MoG (RCN-tPA-MoG and RCN-SS-TD-MoG) with the aim of improving RCN-MoG. We assessed and compared in vitro expression, in vivo immunogenicity, and protective efficacy in vaccinated mice challenged intracerebrally with RABV. All three candidates induced significant humoral immune responses, and inoculation with RCN-tPA-MoG or RCN-MoG significantly increased survival after RABV challenge. These results demonstrate the importance of considering molecular elements in the design of vaccines, and that vaccination with either RCN-tPA-MoG or RCN-MoG confers adequate protection from rabies infection, and either may be a sufficient vaccine candidate for bats in future work.

Vaccines↗

Evaluation of Francisella orientalis ΔpdpA as a live attenuated vaccine against piscine Francisellosis in Nile tilapia

Francisella orientalis is an important bacterial pathogen of marine and freshwater fish with worldwide distribution. Fish francisellosis is a severe subacute to chronic granulomatous disease, with high mortalities and high infectivity rates in cultured and wild fish. To date, there is no approved vaccine for this disease. In this study, we evaluated the efficacy of a defined F. orientalis pathogenicity determinant protein A ( pdpA ) mutant (Δ pdpA ) as a live attenuated immersion vaccine against subsequent immersion challenge with the wild-type organism. Immunized Nile tilapia Oreochromis niloticus were protected (45% relative percent survival) from the lethal challenges and presented significantly lower mortality than nonvaccinated and challenged treatments. Although serum IgM was significantly higher in immunized fish, similar bacterial loads were detected in vaccinated and nonvaccinated survivors. In conclusion, although the F. orientalis Δ pdpA is attenuated and effectively stimulated an adaptive immune response, the low relative percent survival and high bacterial persistence in survivors of immunized and challenged treatments indicates low suitability of Δ pdpA as a mucosal vaccine for tilapia under conditions used in this study.

Journal of Aquatic Animal Health↗

Recombinant F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against virulent Yersinia pestis infection

Black-footed ferrets (Mustela nigripes) are highly susceptible to sylvatic plague, caused by the bacterium Yersinia pestis, and this disease has severely hampered efforts to restore ferrets to their historic range. A study was conducted to assess the efficacy of vaccination of black-footed ferrets against plague using a recombinant protein vaccine, designated F1-V, developed by personnel at the U.S. Army Medical Research Institute of Infectious Diseases. Seven postreproductive black-footed ferrets were immunized with the vaccine, followed by two booster immunizations on days 23 and 154; three control black-footed ferrets received a placebo. After the second immunization, antibody titers to both F1 and V antigen were found to be significantly higher in vaccinates than controls. On challenge with 7,800 colony-forming units of virulent plague by s.c. injection, the three control animals died within 3 days, but six of seven vaccinates survived with no ill effects. The seventh vaccinate died on day 8. These results indicate that black-footed ferrets can be immunized against plague induced by the s.c. route, similar to fleabite injection.

Journal of Zoo and Wildlife Medicine↗

Evolutionary dynamics of an expressed MHC class IIβ locus in the Ranidae (Anura) uncovered by genome walking and high-throughput amplicon sequencing

The Major Histocompatibility Complex (MHC) is a genomic region encoding immune loci that are important and frequently used markers in studies of adaptive genetic variation and disease resistance. Given the primary role of infectious diseases in contributing to global amphibian declines, we characterized the hypervariable exon 2 and flanking introns of the MHC Class IIβ chain for 17 species of frogs in the Ranidae, a speciose and cosmopolitan family facing widespread pathogen infections and declines. We find high levels of genetic variation concentrated in the Peptide Binding Region (PBR) of the exon. Ten codons are under positive selection, nine of which are located in the mammal-defined PBR. We hypothesize that the tenth codon (residue 21) is an amphibian-specific PBR site that may be important in disease resistance. Trans-species and trans-generic polymorphisms are evident from exon-based genealogies, and co-phylogenetic analyses between intron, exon and mitochondrial based reconstructions reveal incongruent topologies, likely due to different locus histories. We developed two sets of barcoded adapters that reliably amplify a single and likely functional locus in all screened species using both 454 and Illumina based sequencing methods. These primers provide a resource for multiplexing and directly sequencing hundreds of samples in a single sequencing run, avoiding the labour and chimeric sequences associated with cloning, and enabling MHC population genetic analyses. Although the primers are currently limited to the 17 species we tested, these sequences and protocols provide a useful genetic resource and can serve as a starting point for future disease, adaptation and conservation studies across a range of anuran taxa.

Developmental and Comparative Immunology↗

White-nose syndrome in bats: U.S. Geological Survey updates

White-nose syndrome (WNS) is a devastating disease that has killed millions of hibernating bats since it first appeared in New York in 2007 and has spread at an alarming rate from the northeastern to the central United States and Canada. The disease is named for the white fungus Geomyces destructans that infects the skin of the muzzle, ears, and wings of hibernating bats. The U.S. Geological Survey (USGS) National Wildlife Health Center (NWHC), the USGS Fort Collins Science Center, the U.S. Fish and Wildlife Service, and other partners continue to play a primary role in WNS research. Studies conducted at the NWHC led to the discovery (Blehert and others, 2009), characterization, and naming (Gargas and others, 2009) of the cold-loving fungus G. destructans and to the development of standardized criteria for diagnosing the disease (Meteyer and others, 2009). Additionally, scientists at the NWHC have pioneered laboratory techniques for studying the effects of the fungus on hibernating bats (Lorch and others, 2011). To determine if bats are affected by white-nose syndrome, scientists look for a characteristic microscopic pattern of skin erosion caused by G. destructans (Meteyer and others, 2009). Field signs of WNS can include visible white fungal growth on the bat's muzzle, wings, or both, but these signs alone are not a reliable disease indicator - laboratory examination and testing are required for disease confirmation. Infected bats also arouse from hibernation more frequently than uninfected bats (Warnecke and others, 2012) and often display abnormal behaviors in their hibernation sites, such as congregating at or near cave openings and daytime flights during winter. These abnormal behaviors may contribute to the bat's accelerated consumption of stored fat reserves, causing emaciation, a characteristic documented in some of the bats that die with WNS. During hibernation, bats likely have lowered immunity (Bouma and others, 2010), which may facilitate the ability of G. destructans to colonize and damage large areas of wing membrane (fig. 2). A current hypothesis suggests that erosion or ulceration of wing membrane caused by the fungus has the potential to alter the physiology of hibernating bats, resulting in fatal disruption of hydration, electrolyte balance, circulation, and thermoregulation (Cryan and others, 2010). Current estimates of bat population declines in the northeastern United States since the emergence of WNS are over 80 percent (Turner and others, 2011). This sudden and widespread mortality associated with WNS is unprecedented in hibernating bats, among which large-scale disease outbreaks have not been previously documented. It is unlikely that species of bats affected by WNS will recover quickly because most are long-lived and have only a single pup per year. Consequently, repopulation after widespread mortality of breeding adults will be a slow process. Worldwide, bats play essential roles as pollinators, seed dispersers, and as primary consumers of insects. The true ecological consequences of the recent large-scale reductions in populations of hibernating bats are not yet known. However, farmers might feel the impact. A recent economic analysis indicated that insect control services (ecosystem services) provided by bats to U.S. agriculture is valued between 4 to 50 billion dollars nationwide per year (Boyles and others, 2011). The number of North American bats estimated to have died from WNS thus far had the capacity to consume up to 8,000 tons of insects per year (Boyles and others, 2011). The area of North America affected by WNS continues to expand. Within the last 2 years, the disease has been confirmed in several Central States, including Alabama, Indiana, Kentucky, Ohio, Tennessee, and Missouri. High mortality of bats has not yet been reported at these locations, and it remains to be seen if WNS will develop and manifest in other States with the same severity as that in the Northeast.

Alabama;Connecticut;Delaware;Illinois;Indiana;Iowa↗

Herring Disease Program II 19120111-E - 2019 Annual Report

We will investigate fish health factors that may be contributing to the failed recovery of Pacific herring populations in Prince William Sound. Field samples will provide infection and disease prevalence data from Prince William Sound and Sitka Sound that will inform the ASA model, serological data that will indicate the prior exposure history and future susceptibility of herring to VHS, and diet information that will provide insights into the unusually high prevalence of Ichthyophonus that occurs in juvenile herring from Cordova Harbor. Laboratory studies will validate the newly-developed plaque neutralization assay as a quantifiable measure of herd immunity against VHS, provide further understanding of disease cofactors including temperature and salinity, investigate the possibility of an invertebrate host for Ichthyophonus, and assess the virulence of other endemic pathogens to Pacific herring. Information from the field and laboratory studies will be integrated into the current ASA model, a novel ASA-type model that is based on the immune status of herring age cohorts.

Alaska↗

Herring Disease Program - Annual Project Report 2012011-E, February 1, 2010-January 31, 2021

We will investigate fish health factors that may be contributing to the failed recovery of Pacific herring populations in Prince William Sound. Field samples will provide infection and disease prevalence data from Prince William Sound and Sitka Sound to inform the age structured assessment (ASA) model, serological data will indicate the prior exposure history and future susceptibility of herring to viral hemorrhagic septicemia virus (VHSV), and diet information will provide insights into the unusually high prevalence of Ichthyophonus that occurs in juvenile herring from Cordova Harbor. Laboratory studies will validate the newly developed plaque neutralization assay as a quantifiable measure of herd immunity against VHS, provide further understanding of disease cofactors including salinity, and investigate possible routes of transmission for Ichthyophonus. Information from the field and laboratory studies will be integrated into the current ASA model and inform a novel ASA-type model that is based on the immune status of herring age cohorts.

Alaska↗

Antibiotic use during the intracoelomic implantation of electronic tags into fish

The use of antibiotics, in particular, the use of a single dose of antibiotics during electronic tag implantation is of unproven value, and carries with it the potential for the development of antibiotic resistance in bacteria and the alteration of the immune response of the fish. Antibiotic use during electronic tag implantation must conform to relevant drug laws and regulations in the country where work is being done, including the requirements for withdrawal times before human consumption is a possibility. Currently, the choice of antibiotics (most often tetracycline or oxytetracycline) and the use of a single dose of the drug are decisions made without knowledge of the basic need for antibiotic usage and of the bacteria involved in infections that occur following electronic tag implantation. Correct perioperative use of an antibiotic is to apply the drug to the animal before surgery begins, to assure serum and tissue levels of the drug are adequate before the incision is made. However, the most common perioperative application of antibiotics during implantation of an electronic tag is to delay the administration of the drug, injecting it into the coelom after the electronic tag is inserted, just prior to closure of the incision. There is little empirical evidence that the present application of antibiotics in fish being implanted with electronic tags is of value. Improvements should first be made to surgical techniques, especially the use of aseptic techniques and sterilized instruments and electronic tags, before resorting to antibiotics.

Reviews in Fish Biology and Fisheries↗

Aroclor 1254 exposure reduces disease resistance and innate immune responses in fasted arctic charr

To examine the immunological impacts of polychlorinated biphenyls (PCBs) in an environmentally relevant way, we orally contaminated Arctic charr (Salvelinus alpinus) with Aroclor 1254. After contamination, fish were either fed (0 and 100 mg Aroclor 1254 kg-1 fish wt) or fasted (0, 1, 10, and 100 mg kg-1) to mimic cycles of feeding-fasting experienced by Arctic animals. After four months, PCB concentrations in muscle were the same in fasted and fed fish; however, PCBs in kidneys of fed fish were 33 to 50% of those in fasted fish. Arctic charr were exposed to Aeromonas salmonicida, the bacteria responsible for furunculosis, by cohabitation with infected conspecifics. Fasted fish had a significant trend toward lower survival with higher dose of PCBs - from 68% in controls to 48% in treatment involving 100 mg kg-1. Independent of PCB contamination, fed fish had the lowest survival; we attribute this to stress associated with establishing and maintaining feeding hierarchies. A significant decrease in the activity of lysozyme was observed in skin mucus, as was hemagglutination ability of a putative rhamnose lectin in fasted, but not in fed, PCB-treated fish. These results demonstrate the immunosuppressive effects of PCBs on Arctic charr, and they illustrate the importance of considering environmentally relevant nutritional status in ecotoxicological studies.

Environmental Toxicology and Chemistry↗

West nile virus in American white pelican chicks: transmission, immunity, and survival

West Nile virus (WNV) causes significant mortality of American White Pelican chicks at northern plains colonies. We tested oropharyngeal/cloacal swabs from moribund chicks for shed WNV. Such shedding could enable chick-to-chick transmission and help explain why WNV spreads rapidly in colonies. WNV was detected on swabs from 11% of chicks in 2006 and 52% of chicks in 2007; however, viral titers were low. Before onset of WNV mortality, we tested blood from < 3-week-old chicks for antibodies to WNV; 5% of chicks were seropositive, suggesting passive transfer of maternal antibodies. Among near-fledged chicks, 41% tested positive for anti-WNV antibodies, indicating that they survived infection. Among years and colonies, cumulative incidence of WNV in chicks varied from 28% to 81%, whereas the proportion of chicks surviving WNV (i.e., seropositive) was 64–75%. Our data revealed that WNV kills chicks that likely would fledge in the absence of WNV, that infection of chicks is pervasive, and that significant numbers of chicks survive infection.

American Journal of Tropical Medicine and Hygiene↗

Antibody response of endangered riparian brush rabbits to vaccination against rabbit hemorrhagic disease virus 2

Rabbit hemorrhagic disease virus 2 (RHDV2; Caliciviridae , Lagovirus europaeus ), the cause of a highly transmissible and fatal lagomorph disease, has spread rapidly through the western United States and Mexico, resulting in substantial mortality in domestic and wild rabbits. The disease was first detected in California in May 2020, prompting an interagency/zoo/academia/nonprofit team to implement emergency conservation actions to protect endangered riparian brush rabbits ( Sylvilagus bachmani riparius ) from RHDV2. Prior to vaccinating wild rabbits, we conducted a vaccine safety trial by giving a single SC dose of Filavac VHD K C+V (Filavie) vaccine to 19 adult wild riparian brush rabbits captured and temporarily held in captivity. Rabbits were monitored for adverse effects, and serum was collected before vaccination, and at 7–10, 14–20, and 60 d post-vaccination. Sera were tested using an ELISA to determine antibody response and timing of seroconversion. Reverse-transcription quantitative real-time PCR (RT-qPCR) was performed on rectal swabs to evaluate infection status. No adverse effects from the vaccine were observed. Before vaccination, 18 of 19 rabbits were seronegative, and RHDV2 was not detected by RT-qPCR on any rectal swabs. After vaccination, all rabbits developed an antibody response, with titers of 1:10–1:160. Seroconversion generally occurred at 7–10 d. The duration of antibody response was ≥60 d in 12 of 13 rabbits. Sixteen animals were released and 4 were recaptured several months later, offering a glimpse into longer duration immune response. Our study has informed vaccination strategies for this species and serves as a model for protecting other vulnerable lagomorphs against RHDV2.

California↗

An examination of the effect of aerosolized permanone insecticide on zebra finch susceptibility to West Nile virus

West Nile virus is primarily maintained cryptically primarily in avian (Passerine) populations where it is transmitted by Culex spp . mosquitoes. Mosquito control measures currently include physical activities to reduce mosquito breeding sites, the application of mosquito larvicides, or aerosolized insecticides to kill adults (adulticides) when arboviral diseases such as West Nile virus (WNV) or Zika virus are detected in mosquito populations. Organochlorine, organohosphorus, carbamate and pyrethroid insecticides are often used. Previous work suggests an effect of pyrethroids on the immune system in a variety of vertebrates. We examined the effects of exposure to aerosolized Permanone ® 30:30 insecticide (permethrin and piperonyl butoxide in soy oil vehicle) at ∼10 3 −10 6 x potential environmental concentrations on the response of captive zebra finches (Taeniopygia guttata) to experimental challenge with WNV. Compared to vehicle control birds, WNV outcome was unchanged (65% of birds produced a viremia) in the ‘low’ exposure (9.52 mg/m 3 ±3.13 SD permethrin) group, but reduced in the ‘high’ exposure (mean 376.5 mg/m 3 ±27.9 SD permethrin) group (30% were viremic) ( p < 0.05). After clearing WNV infection, birds treated with Permanone regained less body mass than vehicle treated birds ( p < 0.001). Our study suggests that exposure to aerosolized Permanone insecticide at levels exceeding typical application rates has the potential to not change or mildly enhance a bird's resistance to WNV.

Environmental Toxicology and Chemistry↗

The aerosphere as a network connector of organisms and their diseases

Aeroecological processes, especially powered flight of animals, can rapidly connect biological communities across the globe. This can have profound consequences for evolutionary diversification, energy and nutrient transfers, and the spread of infectious diseases. The latter is of particular consequence for human populations, since migratory birds are known to host diseases which have a history of transmission into domestic poultry or even jumping to human hosts. In this chapter, we present a scenario under which a highly pathogenic avian influenza (HPAI) strain enters North America from East Asia via post-molting waterfowl migration. We use an agent-based model (ABM) to simulate the movement and disease transmission among 10 6 generalized waterfowl agents originating from ten molting locations in eastern Siberia, with the HPAI seeded in only ~10 2 agents at one of these locations. Our ABM tracked the disease dynamics across a very large grid of sites as well as individual agents, allowing us to examine the spatiotemporal patterns of change in virulence of the HPAI infection as well as waterfowl host susceptibility to the disease. We concurrently simulated a 12-station disease monitoring network in the northwest USA and Canada in order to assess the potential efficacy of these sites to detect and confirm the arrival of HPAI. Our findings indicated that HPAI spread was initially facilitated but eventually subdued by the migration of host agents. Yet, during the 90-day simulation, selective pressures appeared to have distilled the HPAI strain to its most virulent form (i.e., through natural selection), which was counterbalanced by the host susceptibility being conversely reduced (i.e., through genetic predisposition and acquired immunity). The monitoring network demonstrated wide variation in the utility of sites; some were clearly better at providing early warnings of HPAI arrival, while sites further from the disease origin exposed the selective dynamics which slowed the spread of the disease albeit with the result of passing highly virulent strains into southern wintering locales (where human impacts are more likely). Though the ABM presented had generalized waterfowl migration and HPAI disease dynamics, this exercise demonstrates the power of such simulations to examine the extremely large and complex processes which comprise aeroecology. We offer insights into how such models could be further parameterized to represent HPAI transmission risks as well as how ABMs could be applied to other aeroecological questions pertaining to individual-based connectivity.

Book chapter↗

Recombinant raccoon pox vaccine protects mice against lethal plague

Using a raccoon poxvirus (RCN) expression system, we have developed new recombinant vaccines that can protect mice against lethal plague infection. We tested the effects of a translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen in tissue culture and the induction of antibody responses and protection against Yersinia pestis challenge in mice. The RCN vector successfully expressed the F1 protein of Y. pestis in vitro. In addition, the level of expression was increased by the insertion of the EMCV-IRES and combinations of this and the secretory signal or secretory and anchoring signals. These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis . Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7×10 4 LD 50 ). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge. Our studies demonstrate, in vitro and in vivo, the potential importance of the EMCV-IRES and secretory signals in vaccine design. These molecular tools provide a new approach for improving the efficacy of vaccines. In addition, these novel recombinant vaccines could have human, veterinary, and wildlife applications in the prevention of plague.

Vaccine↗