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Peter Timms - One of the best experts on this subject based on the ideXlab platform.
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antibody response against Koala retrovirus korv in Koalas harboring korv a in the presence or absence of korv b
Scientific Reports, 2019Co-Authors: Olusola Olagoke, Bonnie L. Quigley, M V Eiden, Peter TimmsAbstract:Koala retrovirus (KoRV) is in the process of endogenization into the Koala (Phascolarctos cinereus) genome and is currently spreading through the Australian Koala population. Understanding how the Koala’s immune system responds to KoRV infection is critical for developing an efficacious vaccine to protect Koalas. To this end, we analyzed the antibody response of 235 wild Koalas, sampled longitudinally over a four-year period, that harbored KoRV-A, and with or without KoRV-B. We found that the majority of the sampled Koalas were able to make anti-KoRV antibodies, and that there was a linear increase in anti-KoRV IgG levels in Koalas up to approximately seven years of age and then a gradual decrease thereafter. Koalas infected with both KoRV-A and KoRV-B were found to have slightly higher anti-KoRV IgG titers than Koalas with KoRV-A alone and there was an inverse relationship between anti-KoRV IgG levels and circulating KoRV viral load. Finally, we identified distinct epitopes on the KoRV envelope protein that were recognized by antibodies. Together, these findings provide insight into the Koala’s immune response to KoRV and may be useful in the development of a therapeutic KoRV vaccine.
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Chlamydia pecorum prevalence in South Australian Koala (Phascolarctos cinereus) populations: Identification and modelling of a population free from infection
Scientific Reports, 2019Co-Authors: J Fabijan, Adam Polkinghorne, Lucy Woolford, Charles G B Caraguel, Martina Jelocnik, Elisa Nishimoto, Greg Johnsson, Robyn Molsher, Wayne S. J. Boardman, Peter TimmsAbstract:Chlamydia pecorum is an established and prevalent infection that produces severe clinical disease in many Koala populations, contributing to dramatic population declines. In wild South Australian Koala populations, C . pecorum occurrence and distribution is unknown. Here, C . pecorum- specific real-time quantitative PCR (qPCR) was applied to ocular and urogenital swabs from targeted surveys of wild Koalas from the mainland Mount Lofty Ranges (MLR) (n = 75) and Kangaroo Island (KI) (n = 170) populations. Historical data from 13,081 KI Koalas (1997–2018) provided additional evidence for assessing the absence of C . pecorum infection. In the MLR population, 46.7% (CI: 35.1–58.6%) of Koalas were C . pecorum positive by qPCR but only 4% had grade 3 clinical disease. MLR Koala fertility was significantly reduced by C . pecorum infection; all reproductively active females (n = 16) were C . pecorum negative, whereas 85.2% of inactive females (n = 23) were positive (P
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chlamydia pecorum prevalence in south australian Koala phascolarctos cinereus populations identification and modelling of a population free from infection
Scientific Reports, 2019Co-Authors: J Fabijan, Adam Polkinghorne, Wayne Boardman, Lucy Woolford, Charles G B Caraguel, Martina Jelocnik, Elisa Nishimoto, Greg Johnsson, Robyn Molsher, Peter TimmsAbstract:Chlamydia pecorum is an established and prevalent infection that produces severe clinical disease in many Koala populations, contributing to dramatic population declines. In wild South Australian Koala populations, C. pecorum occurrence and distribution is unknown. Here, C. pecorum-specific real-time quantitative PCR (qPCR) was applied to ocular and urogenital swabs from targeted surveys of wild Koalas from the mainland Mount Lofty Ranges (MLR) (n = 75) and Kangaroo Island (KI) (n = 170) populations. Historical data from 13,081 KI Koalas (1997–2018) provided additional evidence for assessing the absence of C. pecorum infection. In the MLR population, 46.7% (CI: 35.1–58.6%) of Koalas were C. pecorum positive by qPCR but only 4% had grade 3 clinical disease. MLR Koala fertility was significantly reduced by C. pecorum infection; all reproductively active females (n = 16) were C. pecorum negative, whereas 85.2% of inactive females (n = 23) were positive (P < 0.001). KI Koalas were C. pecorum negative and the population was demonstrated to be free of C. pecorum infection with 95% confidence. C. pecorum is a real threat for the sustainability of the Koala and KI is possibly the last isolated, large C. pecorum-free population remaining in Australia. These Koalas could provide a safeguard against this serious disease threat to an iconic Australian species.
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Characterisation of MHC class I genes in the Koala
Immunogenetics, 2018Co-Authors: Yuanyuan Cheng, Peter Timms, Adam Polkinghorne, Elizabeth A. Jones, Amber Gillett, Denis O’meally, Katherine BelovAbstract:Koala ( Phascolarctos cinereus ) populations are on the decline across the majority of Australia’s mainland. Two major diseases threatening the long-term survival of affected Koala populations are caused by obligate intracellular pathogens: Chlamydia and Koala retrovirus (KoRV). To improve our understanding of the Koala immune system, we characterised their major histocompatibility complex (MHC) class I genes, which are centrally involved in presenting foreign peptides derived from intracellular pathogens to cytotoxic T cells. A total of 11 class I genes were identified in the Koala genome. Three genes, Phci-UA , UB and UC , showed relatively high genetic variability and were expressed in all 12 examined tissues, whereas the other eight genes had tissue-specific expression and limited polymorphism. Evidence of diversifying selection was detected in Phci-UA and UC , while gene conversion may have played a role in creating new alleles at Phci-UB . We propose that Phci-UA , UB and UC are likely classical MHC genes of Koalas, and further research is needed to understand their role in Koala chlamydial and KoRV infections.
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Koala immunology and infectious diseases: How much can the Koala bear?
Developmental and comparative immunology, 2018Co-Authors: Danielle Madden, Peter Timms, Katherine Belov, Alessandra D. Whaite, Elizabeth A. Jones, Adam PolkinghorneAbstract:Infectious diseases are contributing to the decline of the iconic Australian marsupial, the Koala (Phascolarctos cinereus). Infections with the obligate intracellular bacteria, Chlamydia pecorum, cause debilitating ocular and urogenital-tract disease while the Koala-retrovirus (KoRV) has been implicated in host immunosuppression and exacerbation of chlamydial pathogenesis. Although histological studies have provided insight into the basic architecture of Koala immune tissues, our understanding of the Koala immune response to infectious disease has been limited, until recently, by a lack of species-specific immune reagents. Recent advances in the characterisation of key immune genes have focused on advancing our understanding of the immune response to Chlamydia infection, revealing commonalities in disease pathologies and immunity between Koalas and other hosts and paving the way for the development of a Koala Chlamydia vaccine. This review summarises these recent findings and highlights key aspects of the Koala immune system requiring further attention with particular regard to their most prominent infectious diseases.
Adam Polkinghorne - One of the best experts on this subject based on the ideXlab platform.
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chlamydia pecorum prevalence in south australian Koala phascolarctos cinereus populations identification and modelling of a population free from infection
Scientific Reports, 2019Co-Authors: J Fabijan, Adam Polkinghorne, Wayne Boardman, Lucy Woolford, Charles G B Caraguel, Martina Jelocnik, Elisa Nishimoto, Greg Johnsson, Robyn Molsher, Peter TimmsAbstract:Chlamydia pecorum is an established and prevalent infection that produces severe clinical disease in many Koala populations, contributing to dramatic population declines. In wild South Australian Koala populations, C. pecorum occurrence and distribution is unknown. Here, C. pecorum-specific real-time quantitative PCR (qPCR) was applied to ocular and urogenital swabs from targeted surveys of wild Koalas from the mainland Mount Lofty Ranges (MLR) (n = 75) and Kangaroo Island (KI) (n = 170) populations. Historical data from 13,081 KI Koalas (1997–2018) provided additional evidence for assessing the absence of C. pecorum infection. In the MLR population, 46.7% (CI: 35.1–58.6%) of Koalas were C. pecorum positive by qPCR but only 4% had grade 3 clinical disease. MLR Koala fertility was significantly reduced by C. pecorum infection; all reproductively active females (n = 16) were C. pecorum negative, whereas 85.2% of inactive females (n = 23) were positive (P < 0.001). KI Koalas were C. pecorum negative and the population was demonstrated to be free of C. pecorum infection with 95% confidence. C. pecorum is a real threat for the sustainability of the Koala and KI is possibly the last isolated, large C. pecorum-free population remaining in Australia. These Koalas could provide a safeguard against this serious disease threat to an iconic Australian species.
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Chlamydia pecorum prevalence in South Australian Koala (Phascolarctos cinereus) populations: Identification and modelling of a population free from infection
Scientific Reports, 2019Co-Authors: J Fabijan, Adam Polkinghorne, Lucy Woolford, Charles G B Caraguel, Martina Jelocnik, Elisa Nishimoto, Greg Johnsson, Robyn Molsher, Wayne S. J. Boardman, Peter TimmsAbstract:Chlamydia pecorum is an established and prevalent infection that produces severe clinical disease in many Koala populations, contributing to dramatic population declines. In wild South Australian Koala populations, C . pecorum occurrence and distribution is unknown. Here, C . pecorum- specific real-time quantitative PCR (qPCR) was applied to ocular and urogenital swabs from targeted surveys of wild Koalas from the mainland Mount Lofty Ranges (MLR) (n = 75) and Kangaroo Island (KI) (n = 170) populations. Historical data from 13,081 KI Koalas (1997–2018) provided additional evidence for assessing the absence of C . pecorum infection. In the MLR population, 46.7% (CI: 35.1–58.6%) of Koalas were C . pecorum positive by qPCR but only 4% had grade 3 clinical disease. MLR Koala fertility was significantly reduced by C . pecorum infection; all reproductively active females (n = 16) were C . pecorum negative, whereas 85.2% of inactive females (n = 23) were positive (P
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characterization of shifts of Koala phascolarctos cinereus intestinal microbial communities associated with antibiotic treatment
PeerJ, 2018Co-Authors: Katherine E Dahlhausen, Adam Polkinghorne, Ladan Doroud, Alana Firl, Jonathan A EisenAbstract:Koalas (Phascolarctos cinereus) are arboreal marsupials native to Australia that eat a specialized diet of almost exclusively eucalyptus leaves. Microbes in Koala intestines are known to break down otherwise toxic compounds, such as tannins, in eucalyptus leaves. Infections by Chlamydia, obligate intracellular bacterial pathogens, are highly prevalent in Koala populations. If animals with Chlamydia infections are received by wildlife hospitals, a range of antibiotics can be used to treat them. However, previous studies suggested that Koalas can suffer adverse side effects during antibiotic treatment. This study aimed to use 16S rRNA gene sequences derived from Koala feces to characterize the intestinal microbiome of Koalas throughout antibiotic treatment and identify specific taxa associated with Koala health after treatment. Although differences in the alpha diversity were observed in the intestinal flora between treated and untreated Koalas and between Koalas treated with different antibiotics, these differences were not statistically significant. The alpha diversity of microbial communities from Koalas that lived through antibiotic treatment versus those who did not was significantly greater, however. Beta diversity analysis largely confirmed the latter observation, revealing that the overall communities were different between Koalas on antibiotics that died versus those that survived or never received antibiotics. Using both machine learning and OTU (operational taxonomic unit) co-occurrence network analyses, we found that OTUs that are very closely related to Lonepinella Koalarum, a known tannin degrader found by culture-based methods to be present in Koala intestines, was correlated with a Koala's health status. This is the first study to characterize the time course of effects of antibiotics on Koala intestinal microbiomes. Our results suggest it may be useful to pursue alternative treatments for Chlamydia infections without the use of antibiotics or the development of Chlamydia-specific antimicrobial compounds that do not broadly affect microbial communities.
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Characterisation of MHC class I genes in the Koala
Immunogenetics, 2018Co-Authors: Yuanyuan Cheng, Peter Timms, Adam Polkinghorne, Elizabeth A. Jones, Amber Gillett, Denis O’meally, Katherine BelovAbstract:Koala ( Phascolarctos cinereus ) populations are on the decline across the majority of Australia’s mainland. Two major diseases threatening the long-term survival of affected Koala populations are caused by obligate intracellular pathogens: Chlamydia and Koala retrovirus (KoRV). To improve our understanding of the Koala immune system, we characterised their major histocompatibility complex (MHC) class I genes, which are centrally involved in presenting foreign peptides derived from intracellular pathogens to cytotoxic T cells. A total of 11 class I genes were identified in the Koala genome. Three genes, Phci-UA , UB and UC , showed relatively high genetic variability and were expressed in all 12 examined tissues, whereas the other eight genes had tissue-specific expression and limited polymorphism. Evidence of diversifying selection was detected in Phci-UA and UC , while gene conversion may have played a role in creating new alleles at Phci-UB . We propose that Phci-UA , UB and UC are likely classical MHC genes of Koalas, and further research is needed to understand their role in Koala chlamydial and KoRV infections.
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Koala immunology and infectious diseases: How much can the Koala bear?
Developmental and comparative immunology, 2018Co-Authors: Danielle Madden, Peter Timms, Katherine Belov, Alessandra D. Whaite, Elizabeth A. Jones, Adam PolkinghorneAbstract:Infectious diseases are contributing to the decline of the iconic Australian marsupial, the Koala (Phascolarctos cinereus). Infections with the obligate intracellular bacteria, Chlamydia pecorum, cause debilitating ocular and urogenital-tract disease while the Koala-retrovirus (KoRV) has been implicated in host immunosuppression and exacerbation of chlamydial pathogenesis. Although histological studies have provided insight into the basic architecture of Koala immune tissues, our understanding of the Koala immune response to infectious disease has been limited, until recently, by a lack of species-specific immune reagents. Recent advances in the characterisation of key immune genes have focused on advancing our understanding of the immune response to Chlamydia infection, revealing commonalities in disease pathologies and immunity between Koalas and other hosts and paving the way for the development of a Koala Chlamydia vaccine. This review summarises these recent findings and highlights key aspects of the Koala immune system requiring further attention with particular regard to their most prominent infectious diseases.
Joerg Henning - One of the best experts on this subject based on the ideXlab platform.
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estimating Koala density from incidental Koala sightings in south east queensland australia 1997 2013 using a self exciting spatio temporal point process model
Ecology and Evolution, 2021Co-Authors: Ravi Dissanayake, Rachel Allavena, Emanuele Giorgi, Mark Stevenson, Joerg HenningAbstract:The Koala, Phascolarctos cinereus, is an iconic Australian wildlife species facing a rapid decline in South-East Queensland (SEQLD). For conservation planning, the ability to estimate the size of Koala populations is crucial. Systematic surveys are the most common approach to estimate Koala populations but because of their cost they are often restricted to small geographic areas and are conducted infrequently. Public interest and participation in the collection of Koala sighting data is increasing in popularity, but such data are generally not used for population estimation. We modeled monthly sightings of Koalas reported by members of the public from 1997 to 2013 in SEQLD by developing a self-exciting spatio-temporal point process model. This allowed us to account for characteristics that are associated with Koala presence (which vary over both space and time) while accounting for detection bias in the Koala sighting process and addressing spatial clustering of observations. The density of Koalas varied spatially due to the heterogeneous nature of Koala habitat in SEQLD, with a mean density of 0.0019 Koalas per km2 over the study period. The percentage of land areas with very low densities (0–0.0005 Koalas per km2) remained similar throughout the study period representing, on average, 66% of the total study area. The approach described in this paper provides a useful starting point to allow greater use to be made of incidental Koala sighting data. We propose that the model presented here could be used to combine systematic Koala survey data (which is spatially restricted, but more precise) with Koala sighting data (which is incidental and often biased by nature, but often collected over large geographical areas). Our approach could also be adopted for modeling the density of other wildlife species where data is collected in the same manner.
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The value of long-term citizen science data for monitoring Koala populations
Scientific Reports, 2019Co-Authors: Ravi Bandara Dissanayake, Rachel Allavena, Mark Stevenson, Joerg HenningAbstract:The active collection of wildlife sighting data by trained observers is expensive, restricted to small geographical areas and conducted infrequently. Reporting of wildlife sightings by members of the public provides an opportunity to collect wildlife data continuously over wider geographical areas, at lower cost. We used individual Koala sightings reported by members of the public between 1997 and 2013 in South-East Queensland, Australia ( n = 14,076 Koala sightings) to describe spatial and temporal trends in Koala presence, to estimate Koala sighting density and to identify biases associated with sightings. Temporal trends in sightings mirrored the breeding season of Koalas. Sightings were high in residential areas (63%), followed by agricultural (15%), and parkland (12%). The study area was divided into 57,780 one-square kilometer grid cells and grid cells with no sightings of Koalas decreased over time (from 35% to 21%) indicative of a greater level of spatial overlap of Koala home ranges and human activity areas over time. The density of reported Koala sightings decreased as distance from primary and secondary roads increased, indicative of a higher search effort near roads. Our results show that Koala sighting data can be used to refine Koala distribution and population estimates derived from active surveying, on the condition that appropriate bias correction techniques are applied. Collecting Koala absence and search effort information and conducting repeated searches for Koalas in the same areas are useful approaches to improve the quality of sighting data in citizen science programs.
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Decline causes of Koalas in South East Queensland, Australia: a 17-year retrospective study of mortality and morbidity
Scientific Reports, 2017Co-Authors: Viviana Gonzalez-astudillo, Rachel Allavena, Allan Mckinnon, Rebecca Larkin, Joerg HenningAbstract:Koala populations are in catastrophic decline in certain eastern Australian regions. Spanning from 1997–2013, a database derived from wildlife hospitals in southeast Queensland with N = 20,250 entries was classified by causes of morbidity and mortality. A total of 11 aetiologies were identified, with chlamydiosis, trauma, and wasting being most common. The clinical diagnosis at submission varied significantly over the observation period. Combinations of aetiologies were observed in 39% of Koalas submitted, with chlamydiosis frequently co-occurring. Urogenital (cystitis 26.8%, bursitis 13.5%) and ocular (conjunctivitis 17.2%) chlamydiosis were the most frequently diagnosed representations of the infection. Approximately 26% of submissions comprised Koalas involved in vehicle accidents that were otherwise healthy. Age and sex of the Koala as well as season and submission period were compared for the case outcomes of ‘dead on arrival’, ‘euthanized’, or ‘released’ for the four most common clinical diagnoses using multinomial logistic regression models. Exploratory space-time permutation scans were performed and overlapping space-time clusters for chlamydiosis, motor vehicle traumas and wasting unveiled high risk areas for Koala disease and injury. Our results suggest that these aetiologies are acting jointly as multifactorial determinants for the continuing decline of Koalas.
Kenneth W Beagley - One of the best experts on this subject based on the ideXlab platform.
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characterisation of cd4 t cells in healthy and diseased Koalas phascolarctos cinereus using cell type specific monoclonal antibodies
Developmental and Comparative Immunology, 2016Co-Authors: Chandan Mangar, Peter Timms, Charles W Armitage, Lynn M Corcoran, Kenneth W BeagleyAbstract:The Koala (Phascolarctos cinereus) is an arboreal herbivorous marsupial that is an Australian icon. Koalas in many parts of Australia are under multiple threats including habitat destruction, dog attacks, vehicular accidents, and infectious diseases such as Chlamydia spp. and the Koala retrovirus (KoRV), which may contribute to the incidence of lymphoma and leukaemia in this species. Due to a lack of Koala-specific immune reagents and assays there is currently no way to adequately analyse the immune response in healthy, diseased or vaccinated animals. This paper reports the production and characterisation of the first anti-Koala CD4 monoclonal antibody (mAb). The Koala CD4 gene was identified and used to develop recombinant proteins for mAb production. Fluorochrome-conjugated anti-CD4 mAb was used to measure the levels of CD4+ lymphocytes collected from Koala spleens (41.1%, range 20–45.1%) lymph nodes (36.3%, range 19–55.9%) and peripheral blood (23.8%, range 17.3–35%) by flow cytometry. Biotin-conjugated anti-CD4 mAb was used for western blot to determine an approximate size of 52 kDa for the Koala CD4 molecule and used in immunohistochemistry to identify CD4+ cells in the paracortical region and germinal centres of spleen and lymph nodes. Using the anti-CD4 mab we showed that CD4 cells from vaccinated, but not control, Koalas proliferated following in vitro stimulation with UV-inactivated Chlamydia pecorum and recombinant chlamydial antigens. Since CD4+ T cells have been shown to play a pivotal role in clearing chlamydial infection in both human and mouse infections, using this novel antibody will help determine the role CD4+ T cells play in protection against chlamydial infection in Koalas and also enhance our knowledge of how KoRV affects the Koala immune system.
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humoral immune responses in Koalas phascolarctos cinereus either naturally infected with chlamydia pecorum or following administration of a recombinant chlamydial major outer membrane protein vaccine
Vaccine, 2016Co-Authors: Shahneaz Ali Khan, Courtney Waugh, Adam Polkinghorne, J. Hanger, Kenneth W Beagley, Jo Loader, Peter TimmsAbstract:The development of a vaccine is a key strategy to combat the widespread and debilitating effects of chlamydial infection in Koalas. One such vaccine in development uses recombinant chlamydial major outer membrane protein (rMOMP) as an antigen and has shown promising results in several Koala trials. Previous chlamydial vaccine studies, primarily in the mouse model, suggest that both cell-mediated and antibody responses will be required for adequate protection. Recently, the important protective role of antibodies has been highlighted. In our current study, we conducted a detailed analysis of the antibody-mediated immune response in Koalas that are either (a) naturally-infected, and/or (b) had received an rMOMP vaccine. Firstly, we observed that naturally-infected Koalas had very low levels of Chlamydia pecorum-specific neutralising antibodies. A strong correlation between low IgG total titers/neutralising antibody levels, and higher C. pecorum infection load was also observed in these naturally-infected animals. In vaccinated Koalas, we showed that the vaccine was able to boost the humoral immune response by inducing strong levels of C. pecorum-specific neutralising antibodies. A detailed characterisation of the MOMP epitope response was also performed in naturally-infected and vaccinated Koalas using a PepScan epitope approach. This analysis identified unique sets of MOMP epitope antibodies between naturally-infected non-protected and diseased Koalas, versus vaccinated Koalas, with the latter group of animals producing a unique set of specific epitope-directed antibodies that we demonstrated were responsible for the in vitro neutralisation activity. Together, these results show the importance of antibodies in chlamydial infection and immunity following vaccination in the Koala.
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comparison of subcutaneous versus intranasal immunization of male Koalas phascolarctos cinereus for induction of mucosal and systemic immunity against chlamydia pecorum
Vaccine, 2015Co-Authors: Courtney Waugh, Peter Timms, Jacqui Brumm, Karen Nilsson, Dean Andrew, Galit Rawlinson, Kenneth W BeagleyAbstract:Chlamydia pecorum infections are debilitating in the Koala, contributing significantly to morbidity and mortality, with current antibiotic treatments having minimal success and adversely affecting gut microflora. This, combined with the sometimes-asymptomatic nature of the infection, suggests that an efficacious anti-chlamydial vaccine is required to control chlamydial infections in the Koala. To date vaccination studies have focused primarily on female Koalas, however, given the physiological differences between male and female reproductive tracts, we tested the efficacy of a vaccine in 12 captive male Koalas. We evaluated the potential of both subcutaneous and intranasal vaccine delivery to elicit mucosal immunity in male Koalas. Our results showed that both intranasal and subcutaneous delivery of a vaccine consisting of C. pecorum major outer membrane protein (MOMP) and the adjuvant immunostimulating complex (ISC) induced significant immune responses in male Koalas. Subcutaneous immunization elicited stronger cell-mediated responses in peripheral blood lymphocytes (PBL), and greater plasma antibody levels whereas the intranasal immunization elicited stronger humoral responses in urogenital tract (UGT) secretions. This is the first time a Chlamydia vaccine has been tested in the male Koala and the first assessment of a mucosal vaccination route in this species. Our results suggest that vaccination of male Koalas can elicit mucosal immunity and could contribute to the long-term survivability of wild populations of the Koala.
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interleukin 17a is an immune marker for chlamydial disease severity and pathogenesis in the Koala phascolarctos cinereus
Institute of Health and Biomedical Innovation, 2014Co-Authors: Marina Mathew, Courtney Waugh, Peter Timms, Kenneth W Beagley, Adam PolkinghorneAbstract:The Koala (Phascolarctos cinereus) is an iconic Australian marsupial species that is facing many threats to its survival. Chlamydia pecorum infections are a significant contributor to this ongoing decline. A major limiting factor in our ability to manage and control chlamydial disease in Koalas is a limited understanding of the Koala’s cell-mediated immune response to infections by this bacterial pathogen. To identify immunological markers associated with chlamydial infection and disease in Koalas, we used Koala-specific Quantitative Real Time PCR (qrtPCR) assays to profile the cytokine responses of Peripheral Blood Mononuclear Cells (PBMCs) collected from 41 Koalas with different stages of chlamydial disease. Target cytokines included the principal Th1 (Interferon gamma; IFNγ), Th2 (Interleukin 10; IL10), and pro-inflammatory cytokines (Tumor Necrosis Factor alpha; TNFα). A novel Koala-specific IL17A qrtPCR assay was also developed as part of this study to quantitate the gene expression of this Th17 cytokine in Koalas. A statistically significant higher IL17A gene expression was observed in animals with current chlamydial disease compared to animals with asymptomatic chlamydial infection. A modest up-regulation of pro-inflammatory cytokines, such as TNFα and IFNγ, was also observed in these animals with signs of current chlamydial disease. IL10 gene expression was not evident in the majority of animals from both groups. Future longitudinal studies are now required to confirm the role played by cytokines in pathology and/or protection against C. pecorum infection in the Koala.
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preliminary characterisation of tumor necrosis factor alpha and interleukin 10 responses to chlamydia pecorum infection in the Koala phascolarctos cinereus
PLOS ONE, 2013Co-Authors: Marina Mathew, Peter Timms, Kenneth W Beagley, Adam PolkinghorneAbstract:Debilitating infectious diseases caused by Chlamydia are major contributors to the decline of Australia's iconic native marsupial species, the Koala (Phascolarctos cinereus). An understanding of Koala chlamydial disease pathogenesis and the development of effective strategies to control infections continue to be hindered by an almost complete lack of species-specific immunological reagents. The cell-mediated immune response has been shown to play an influential role in the response to chlamydial infection in other hosts. The objective of this study, hence, was to provide preliminary data on the role of two key cytokines, pro-inflammatory tumour necrosis factor alpha (TNFα) and anti-inflammatory interleukin 10 (IL10), in the Koala Chlamydia pecorum response. Utilising sequence homology between the cytokine sequences obtained from several recently sequenced marsupial genomes, this report describes the first mRNA sequences of any Koala cytokine and the development of Koala specific TNFα and IL10 real-time PCR assays to measure the expression of these genes from Koala samples. In preliminary studies comparing wild Koalas with overt chlamydial disease, previous evidence of C. pecorum infection or no signs of C. pecorum infection, we revealed strong but variable expression of TNFα and IL10 in wild Koalas with current signs of chlamydiosis. The description of these assays and the preliminary data on the cell-mediated immune response of Koalas to chlamydial infection paves the way for future studies characterising the Koala immune response to a range of its pathogens while providing reagents to assist with measuring the efficacy of ongoing attempts to develop a Koala chlamydial vaccine.
J. Hanger - One of the best experts on this subject based on the ideXlab platform.
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Epidemiology of chlamydial infection and disease in a free-ranging Koala (Phascolarctos cinereus) population
PloS one, 2017Co-Authors: Sharon Nyari, Adam Polkinghorne, Courtney A. Waugh, Jianbao Dong, Bonnie L. Quigley, J. Hanger, Joanne Loader, Peter TimmsAbstract:Chlamydial disease continues to be one of the main factors threatening the long-term survival of the Koala (Phascolarctos cinereus). Despite this, large epidemiological studies of chlamydial infection and disease in wild Koala populations are lacking. A better understanding of the prevalence, transmission and pathogenesis is needed to improve control measures, such as the development of vaccines. We investigated the prevalence of Chlamydia pecorum infection and disease in 160 Koalas in a peri-urban wild population in Queensland, Australia and found that 31% of Koalas were Chlamydia PCR positive and 28% had clinically detectable chlamydial disease. Most infections were at the urogenital site (27%; both males and females) with only 14% at the ocular site. Interestingly, we found that 27% (4/15) of Koalas considered to be sexually immature (9–13 months) were already infected with C. pecorum, suggesting that a significant percentage of animals are infected directly from their mother. Ocular infection levels were less prevalent with increasing age (8% in Koalas older than 4 years), whereas the prevalence of urogenital tract infections remained high into older age (26% in Koalas older than 4 years), suggesting that, after mother-to-young transmission, C. pecorum is predominantly a sexually transmitted infection. While 28% of Koalas in this population had clinically detectable chlamydial disease (primarily urogenital tract disease), many PCR positive Koalas had no detectable disease and importantly, not all diseased animals were PCR positive. We also observed higher chlamydial loads in Koalas who were C. pecorum infected without clinical disease than in Koalas who were C. pecorum infected with clinical disease. These results shed light on the potential mechanisms of transmission of C. pecorum in Koalas and also guide future control measures, such as vaccination.
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Microbiota composition of the Koala (Phascolarctos cinereus) ocular and urogenital sites, and their association with Chlamydia infection and disease
Scientific Reports, 2017Co-Authors: Miranda E. Vidgen, J. Hanger, Peter TimmsAbstract:Disease caused by Chlamydia pecorum is characterised by ocular and urogenital infections that can lead to blindness and infertility in Koalas. However, Koalas that are infected with C . pecorum do not always progress to disease. In other host systems, the influence of the microbiota has been implicated in either accelerating or preventing infections progressing to disease. This study investigates the contribution of Koala urogenital and ocular microbiota to Chlamydia infection and disease in a free ranging Koala population. Using univariate and multivariate analysis, it was found that reproductive status in females and sexual maturation in males, were defining features in the Koala urogenital microbiota. Changes in the urogenital microbiota of Koalas is correlated with infection by the common pathogen, C . pecorum . The correlation of microbiota composition and C . pecorum infection is suggestive of members of the microbiota being involved in the acceleration or prevention of infections progressing to disease. The analysis also suggests that multiple microbes are likely to be associated with this process of disease progression, rather than a single organism. While other Chlamydia -like organisms were also detected, they are unlikely to contribute to chlamydial disease as they are rare members of the urogenital and ocular microbiota communities.
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Infection with Koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging Koalas (Phascolarctos cinereus)
Scientific Reports, 2017Co-Authors: Courtney A. Waugh, J. Hanger, Joanne Loader, Andrew King, Matthew Hobbs, Rebecca Johnson, Peter TimmsAbstract:The virulence of chlamydial infection in wild Koalas is highly variable between individuals. Some Koalas can be infected (PCR positive) with Chlamydia for long periods but remain asymptomatic, whereas others develop clinical disease. Chlamydia in the Koala has traditionally been studied without regard to coinfection with other pathogens, although Koalas are usually subject to infection with Koala retrovirus (KoRV). Retroviruses can be immunosuppressive, and there is evidence of an immunosuppressive effect of KoRV in vitro . Originally thought to be a single endogenous strain, a new, potentially more virulent exogenous variant (KoRV-B) was recently reported. We hypothesized that KoRV-B might significantly alter chlamydial disease outcomes in Koalas, presumably via immunosuppression. By studying sub-groups of Chlamydia and KoRV infected Koalas in the wild, we found that neither total KoRV load (either viraemia or proviral copies per genome), nor chlamydial infection level or strain type, was significantly associated with chlamydial disease risk. However, PCR positivity with KoRV-B was significantly associated with chlamydial disease in Koalas ( p = 0.02961). This represents an example of a recently evolved virus variant that may be predisposing its host (the Koala) to overt clinical disease when co-infected with an otherwise asymptomatic bacterial pathogen ( Chlamydia ).
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humoral immune responses in Koalas phascolarctos cinereus either naturally infected with chlamydia pecorum or following administration of a recombinant chlamydial major outer membrane protein vaccine
Vaccine, 2016Co-Authors: Shahneaz Ali Khan, Courtney Waugh, Adam Polkinghorne, J. Hanger, Kenneth W Beagley, Jo Loader, Peter TimmsAbstract:The development of a vaccine is a key strategy to combat the widespread and debilitating effects of chlamydial infection in Koalas. One such vaccine in development uses recombinant chlamydial major outer membrane protein (rMOMP) as an antigen and has shown promising results in several Koala trials. Previous chlamydial vaccine studies, primarily in the mouse model, suggest that both cell-mediated and antibody responses will be required for adequate protection. Recently, the important protective role of antibodies has been highlighted. In our current study, we conducted a detailed analysis of the antibody-mediated immune response in Koalas that are either (a) naturally-infected, and/or (b) had received an rMOMP vaccine. Firstly, we observed that naturally-infected Koalas had very low levels of Chlamydia pecorum-specific neutralising antibodies. A strong correlation between low IgG total titers/neutralising antibody levels, and higher C. pecorum infection load was also observed in these naturally-infected animals. In vaccinated Koalas, we showed that the vaccine was able to boost the humoral immune response by inducing strong levels of C. pecorum-specific neutralising antibodies. A detailed characterisation of the MOMP epitope response was also performed in naturally-infected and vaccinated Koalas using a PepScan epitope approach. This analysis identified unique sets of MOMP epitope antibodies between naturally-infected non-protected and diseased Koalas, versus vaccinated Koalas, with the latter group of animals producing a unique set of specific epitope-directed antibodies that we demonstrated were responsible for the in vitro neutralisation activity. Together, these results show the importance of antibodies in chlamydial infection and immunity following vaccination in the Koala.
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genetic diversity of chlamydia pecorum strains in wild Koala locations across australia and the implications for a recombinant c pecorum major outer membrane protein based vaccine
Veterinary Microbiology, 2013Co-Authors: Avinash Kollipara, John Callaghan, Adam Polkinghorne, J. Hanger, Joanne Loader, Charles Wan, Pride Kanyoka, Alicia Bell, W A Ellis, Sean FitzgibbonAbstract:The long term survival of the Koala (Phascolarctos cinereus) is at risk due to a range of threatening processes. A major contributing factor is disease caused by infection with Chlamydia pecorum, which has been detected in most mainland Koala populations and is associated with ocular and genital tract infections. A critical aspect for the development of vaccines against Koala chlamydial infections is a thorough understanding of the prevalence and strain diversity of C. pecorum infections across wild populations. In this study, we describe the largest survey (403 Koalas from eight wild populations and three wildlife hospitals) examining the diversity of C. pecorum infections. 181 of the 403 Koalas tested (45%) positive for C. pecorum by species-specific quantitative PCR with infection rates ranging from 20% to 61% in the eight wild populations sampled. The ompA gene, which encodes the chlamydial major outer membrane protein (MOMP), has been the major target of several chlamydial vaccines. Based on our analysis of the diversity of MOMP amino types in the infected Koalas, we conclude that, (a) there exists significant diversity of C. pecorum strains in Koalas, with 10 distinct, full length C. pecorum MOMP amino types identified in the 11 Koala locations sampled, (b) despite this diversity, there are predicted T and B cell epitopes in both conserved as well as variable domains of MOMP which suggest cross-amino type immune responses, and (c) a recombinant MOMP-based vaccine consisting of MOMP "F" could potentially induce heterotypic protection against a range of C. pecorum strains.
