Efficacy of Two Chlamydia abortus Subcellular Vaccines in a Pregnant Ewe Challenge Model for Ovine Enzootic Abortion.
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ABSTRACT:
SUBMITTER: Livingstone M
PROVIDER: S-EPMC8402522 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The bacterium Coxiella burnetii can cause the disease Q-fever in a wide range of animal hosts. Ruminants, including sheep, are thought to play a pivotal role in the transmission of C. burnetii to humans; however, the only existing livestock vaccine, namely, Coxevac® (Ceva Animal Health Ltd., Libourne, France), a killed bacterin vaccine based on phase I C. burnetii strain Nine-Mile, is only approved for use in goats and cattle. In this study, a pregnant ewe challenge model was used to determine the protective effects of Coxevac® and an experimental bacterin vaccine based on phase II C. burnetii against C. burnetii challenge. Prior to mating, ewes (n = 20 per group) were vaccinated subcutaneously with either Coxevac®, the phase II vaccine, or were unvaccinated. A subset of pregnant ewes (n = 6) from each group was then challenged 151 days later (~100 days of gestation) with 106 infectious mouse doses of C. burnetii, Nine-Mile strain RSA493. Both vaccines provided protection against C. burnetii challenge as measured by reductions in bacterial shedding in faeces, milk and vaginal mucus, and reduced abnormal pregnancies, compared to unvaccinated controls. This work highlights that the phase I vaccine Coxevac® can protect ewes against C. burnetii infection. Furthermore, the phase II vaccine provided comparable levels of protection and may offer a safer and cost-effective alternative to the currently licensed vaccine.
| S-EPMC10054861 | biostudies-literature
Project description:Ovine enzootic abortion (OEA) resulting from infection of sheep and goats with Chlamydophila abortus is of major economic importance worldwide. Over the last 50 years the serological diagnosis of infection has been based mainly on the complement fixation test (CFT), which lacks both sensitivity and specificity because of cross-reactive antibodies to other gram-negative bacteria, including another common chlamydial pathogen of sheep, Chlamydophila pecorum. In the present study, a series of overlapping recombinant antigens representing the polymorphic outer membrane protein POMP90 of C. abortus was assessed by enzyme-linked immunosorbent assay (ELISA) with a panel of 143 serum samples from sheep experimentally infected with C. abortus, from sheep clinically free of OEA, and from specific-pathogen-free lambs experimentally infected with different subtypes of C. pecorum. The results were compared to those obtained by CFT and another recently described test, an indirect ELISA (iELISA) with the recombinant OMP91B (rOMP91B) fragment (rOMP91B iELISA) (D. Longbottom, E. Psarrou, M. Livingstone, and E. Vretou, FEMS Microbiol. Lett. 195:157-161, 2001). The rOMP90-3 and rOMP90-4 ELISAs were identified as being more sensitive and specific than CFT. Assays with both fragments were evaluated further with a panel of 294 field serum samples from flocks with documented histories of abortion, from flocks with no clinical histories of abortion but which had a high proportion of samples seropositive by CFT, and from animals with no histories of abortion but from which various C. pecorum subtypes had been isolated. ELISAs with both POMP90 fragments outperformed CFT with serum samples from C. pecorum-infected animals, producing no false-positive results. However, the ELISA with the rOMP90-4 fragment appeared to be more sensitive than the one with rOMP90-3, as it identified more of the OEA-positive samples. The ELISA with the rOMP90-4 fragment was also able to identify apparently healthy animals that were infected with an enteric strain of C. abortus in flocks that were probably infected with both enteric C. abortus and C. pecorum strains. The identification of animals infected with enteric C. abortus is extremely important in controlling the spread of OEA. Overall, the new rOMP90-4 ELISA was found to be a more sensitive and specific test than CFT for differentiating animals infected with C. abortus from those infected with C. pecorum.
| S-EPMC139646 | biostudies-literature
Project description:Chlamydia pecorum is a common gastrointestinal inhabitant of livestock but infections can manifest in a broad array of clinical presentations and in a range of host species. While C. pecorum is a known cause of ovine abortion, clinical cases have only recently been described in detail. Here, the prevalence and sequence types (STs) of C. pecorum in ewes from a property experiencing high levels of perinatal mortality (PNM) in New South Wales (NSW), Australia, were investigated using serological and molecular methods. Ewes that were PNM+ were statistically more likely to test seropositive compared to PNM- ewes and displayed higher antibody titres; however, an increase in chlamydial shedding from either the rectum, vagina or conjunctiva of PNM+ ewes was not observed. Multilocus sequence typing (MLST) indicated that C. pecorum ST23 was the major ST shed by ewes in the flock, was the only ST identified from the vaginal site, and was the same ST detected within aborted foetal tissues. Whole genome sequencing of C. pecorum isolated from one abortion case revealed that the C. pecorum plasmid (pCpec) contained a unique deletion in coding sequence 1 (CDS1) that was also present in C. pecorum ST23 shed from the ewes. A further unique deletion was noted in a polymorphic membrane protein gene (pmpG) of the C. pecorum chromosome, which warrants further investigation given the role of PmpG in host cell adherence and tissue tropism.This study describes novel infection parameters in a sheep flock experiencing C. pecorum-associated perinatal mortality, provides the first genomic data from an abortigenic C. pecorum strain, and raises questions about possible links between unique genetic features of this strain and C. pecorum abortion.
| S-EPMC8618313 | biostudies-literature
Project description:Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus.Three groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×10(3), 5×10(5) and 5×10(7) inclusion forming units (IFU), respectively) prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b) or were inoculated subcutaneously on day 70 of gestation with 2×10(6) IFU C. abortus (group 5). Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium.The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and vaccines for controlling infection.
| S-EPMC3585262 | biostudies-other
Project description:Environmental transmission of Chlamydia abortus as a result of enzootic disease or disease outbreaks and the threats posed by this pathogen has been previously reported, however a state-of-the-science review of these reports and the identification of future research priorities in this area is still lacking. This study provides an overview of the current knowledge of host-pathogen-environment interactions, addressing public health risks and identifying critical questions and research gaps. We performed a systematic PubMed and Web of Science search for publications related to Chlamydia abortus in the past four decades, and we reviewed and combined the evidence critically discussing and commenting the results. A total of 182 studies, 5 chapters of specific books and the "OIE terrestrial manual" were included in this review. There were substantial variations between the studies in topic addressed and experimental design. Overall, the literature largely supports the crucial role played by environmental exposure on the acquisition of zoonotic disease caused by Chlamydia abortus. We also identify the paucity of information related to interspecies transmission and pathogen adaptation in relation to environmental dissemination and zoonotic risk. This analysis further highlights the need for additional research given that environmental transmission represents a serious risk not only to susceptible patients (pregnant women and immunocompromised individuals), but also for other species including wildlife.
| S-EPMC9152823 | biostudies-literature
Project description:BackgroundPrevention and control of ovine enzootic abortion (OEA) can be achieved by application of a live vaccine. In this study, five sheep flocks with different vaccination and infection status were serologically tested using a competitive enzyme-linked immunosorbent assay (cELISA) specific for Chlamydophila (Cp.) abortus over a two-year time period.ResultsSheep in Flock A with recent OEA history had high antibody values after vaccination similar to Flock C with natural Cp. abortus infections. In contrast, OEA serology negative sheep (Flock E) showed individual animal-specific immunoreactions after vaccination. Antibody levels of vaccinated ewes in Flock B ranged from negative to positive two and three years after vaccination, respectively. Positive antibody values in the negative control Flock D (without OEA or vaccination) are probably due to asymptomatic intestinal infections with Cp. abortus. Excretion of the attenuated strain of Cp. abortus used in the live vaccine through the eye was not observed in vaccinated animals of Flock E.ConclusionThe findings of our study indicate that, using serology, no distinction can be made between vaccinated and naturally infected sheep. As a result, confirmation of a negative OEA status in vaccinated animals by serology cannot be determined.
| S-EPMC2042495 | biostudies-literature
Project description:Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.
| S-EPMC8219966 | biostudies-literature
Project description:Traditional methods of detecting Chlamydia pecorum in tissue samples such as polymerase chain reaction or cell culture are laborious and costly. We evaluated the use of a previously developed C. pecorum LAMP assay using minimally processed ovine samples. Cotyledon (n = 16), foetal liver (n = 22), foetal lung (n = 2), and vaginal (n = 6) swabs, in addition to cotyledon (n = 6) and foetal liver (n = 8) tissue samples, were rapidly processed and used for LAMP testing without DNA extraction. Overall, LAMP test results were highly congruent with the in-house reference qPCR, with 80.43% (37/46; 72.73% positive agreement (PA); 84.75% negative agreement (NA)) overall agreeance for swab samples, and 85.71% (12/14; 80% PA; 88.89% NA) overall agreeance for tissue samples. Out of the 11 total discrepant results, discrepancy was mainly observed in samples (n = 10) with less than 100 copies/µL C. pecorum DNA. While sensitivity could be improved, the simplicity, low cost, and accuracy of detection makes this test amenable for use at point-of-care for detecting C. pecorum in sheep.
| S-EPMC8470028 | biostudies-literature
Project description:Enzootic nasal tumor virus (ENTV-1) is an ovine betaretrovirus that has been linked to enzootic nasal adenocarcinoma (ENA), a contagious tumor of the ethmoid turbinates of sheep. Transmission experiments performed using virus isolated from cell free nasal tumor homogenates suggest that ENTV-1 is the causative agent of ENA; however, this etiological relationship has not been conclusively proven due to the fact that the virus cannot be propagated in vitro nor is there an infectious molecular clone of the virus.Here we report construction of a molecular clone of ENTV-1 and demonstrate that transfection of this molecular clone into HEK 293T cells produces mature virus particles.Analysis of recombinant virus particles derived from the initial molecular clone revealed a defect in the proteolytic processing of Gag; however, this defect could be corrected by co-expression of the Gag-Pro-Pol polyprotein from the highly related Jaagsiekte sheep retrovirus (JSRV) suggesting that the polyprotein cleavage sites in the ENTV-1 molecular clone were functional. Mutagenesis of the molecular clone to correct amino acid variants identified within the pro gene did not restore proteolytic processing; whereas deletion of one proline residue from a polyproline tract located in variable region 1 (VR1) of the matrix resulted in production of CA protein of the mature (cleaved) size strongly suggesting that normal virion morphogenesis and polyprotein cleavage took place. Finally, electron microscopy revealed the presence of spherical virus particles with an eccentric capsid and an average diameter of about 100 nm.In summary, we have constructed the first molecular clone of ENTV-1 from which mature virus particles can be produced. Future experiments using virus produced from this molecular clone can now be conducted to fulfill Koch's postulates and demonstrate that ENTV-1 is necessary and sufficient to induce ENA in sheep.
| S-EPMC5203713 | biostudies-literature
Project description:IntroductionNovel imaging measurements of placental development are difficult to validate due to the invasive nature of gold-standard procedures. Animal studies have been important in validation of magnetic resonance imaging (MRI) measurements in invasive preclinical studies, as they allow for controlled experiments and analysis of multiple time-points during pregnancy. This study characterises the longitudinal diffusion and perfusion properties of sheep placentomes using MRI, measurements that are required for future validation studies.MethodsPregnant ewes were anaesthetised for a MRI session on a 3T scanner. Placental MRI was used to classify placentomes morphologically into three types based on their shape and size at two gestational ages. To validate classification accuracy, placentome type derived from MRI data were compared with placentome categorisation results after delivery. Diffusion-Weighted MRI and T2-relaxometry were used to measure a broad range of biophysical properties of the placentomes.ResultsMRI morphological classification results showed consistent gestational age changes in placentome shape, as supported by post-delivery gold standard data. The mean apparent diffusion coefficient was significantly higher at 110 days gestation than at late gestation (~140 days; term, 150 days). Mean T2 was higher at mid gestation (152.2 ± 58.1 ms) compared to late gestation (127.8 ms ± 52.0). Significantly higher perfusion fraction was measured in late gestation placentomes that also had a significantly higher fractional anisotropy when compared to the earlier gestational age.DiscussionWe report baseline measurements of techniques common in placental MRI for the sheep placenta. These measurements are essential to support future validation measurements of placental MRI techniques.
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