Restricted dog leucocyte antigen (DLA) class II haplotypes and genotypes in Beagles

AbstractBeagles are commonly used in vaccine trials as part of the regulatory approval process. Genetic restriction within this breed and the impact this might have on vaccine responses are rarely considered. This study was designed to characterise diversity of dog leucocyte antigen (DLA) class II genes in a breeding colony of laboratory Beagles, whose offspring are used in vaccine studies. DLA haplotypes were determined by PCR and sequence-based typing from genomic DNA extracted from blood. Breeding colony Beagles had significantly different DLA haplotype frequencies in comparison with pet Beagles and both groups showed limited DLA diversity. Restricted DLA class II genetic variability within Beagles might result in selective antigen presentation and vaccine responses that are not necessarily representative of those seen in other dog breeds

Poultry Coccidiosis: Design and Interpretation of Vaccine Studies

Eimeria infection impacts upon chicken welfare and economic productivity of the poultry sector. Live coccidiosis vaccines for chickens have been available for almost 70 years, but the requirement to formulate blends of oocysts from multiple Eimeria species makes vaccine production costly and logistically demanding. A multivalent vaccine that does not require chickens for its production and can induce protection against multiple Eimeria species is highly desirable. However, despite the identification and testing of many vaccine candidate antigens, no recombinant coccidiosis vaccine has been developed commercially. Currently, assessment of vaccine efficacy against Eimeria, and the disease coccidiosis, can be done only through in vivo vaccination and challenge experiments but the design of such studies has been highly variable. Lack of a “standard” protocol for assessing vaccine efficacy makes comparative evaluations very difficult, complicating vaccine development, and validation. The formulation and schedule of vaccination, the breed of chicken and choice of husbandry system, the species, strain, magnitude, and timing of delivery of the parasite challenge, and the parameters used to assess vaccine efficacy all influence the outcomes of experimental trials. In natural Eimeria infections, the induction of strong cell mediated immune responses are central to the development of protective immunity against coccidiosis. Antibodies are generally regarded to be of lesser importance. Unfortunately, there are no specific immunological assays that can accurately predict how well a vaccine will protect against coccidiosis (i.e., no “correlates of protection”). Thus, experimental vaccine studies rely on assessing a variety of post-challenge parameters, including assessment of pathognomonic lesions, measurements of parasite replication such as oocyst output or quantification of Eimeria genomes, and/or measurements of productivity such as body weight gain and feed conversion rates. Understanding immune responses to primary and secondary infection can inform on the most appropriate immunological assays. The discovery of new antigens for different Eimeria species and the development of new methods of vaccine antigen delivery necessitates a more considered approach to assessment of novel vaccines with robust, repeatable study design. Careful consideration of performance and welfare factors that are genuinely relevant to chicken producers and vaccine manufacturers is essential

Inconsistent MHC class II association in Beagles experimentally infected with Leishmania infantum

The clinical outcome of Leishmania infantum infection in dogs varies from subclinical infection to severe disease. Researchers attribute this variability in clinical manifestations to the ability of the immune response to limit pathogen multiplication and dissemination, which is, in part, likely determined by the immune response genes. The aim of this study was to test the hypothesis that MHC class II genes are associated with disease outcome of experimental L. infantum infection in Beagles. Dog leukocyte antigen (DLA) class II haplotypes were characterised by sequence-based typing of Beagle dogs experimentally infected with L. infantum during vaccine challenge studies. Variability of response to infection was determined by clinical score, serology and quantification of L. infantum DNA in the bone marrow over the study period. Dogs showed limited DLA diversity and the DLA profiles of dogs recruited for the different vaccine challenge studies differed. There were variable responses to infection, despite the apparent restriction in genetic diversity. One haplotype DLA-DRB1*001:02–DQA1*001:01–DQB1*002:01 was associated with increased anti-Leishmania antibodies in one infection model, but no DLA associations were found in other groups or with parasite load or clinical score. Examination of this particular DLA haplotype in a larger number of dogs is required to confirm whether an association exists with the immune or clinical responses to L. infantum infection

Vaccination with transgenic Eimeria tenella expressing Eimeria maxima AMA1 and IMP1 confers partial protection against high level E. maxima challenge in a broiler model of coccidiosis.

Poultry coccidiosis is a parasitic enteric disease with a highly negative impact on chicken production. In-feed chemoprophylaxis remains the primary method of control, but the increasing ineffectiveness of anticoccidial drugs, and potential future restrictions on their use has encouraged the use of commercial live vaccines. Availability of such formulations is constrained by their production, which relies on the use of live chickens. Several experimental approaches have been taken to explore ways to reduce the complexity and cost of current anticoccidial vaccines including the use of live vectors expressing relevant Eimeria proteins. We and others have shown that vaccination with transgenic Eimeria tenella parasites expressing E. maxima Apical Membrane Antigen-1 or Immune Mapped Protein-1 (EmAMA1 and EmIMP1) partially reduces parasite replication after challenge with a low dose of E. maxima oocysts. In the present work we have reassessed the efficacy of these experimental vaccines using commercial birds reared at high stocking densities and challenged with both low and high doses of E. maxima to evaluate how well they protect chickens against the negative impacts of disease on production parameters

An investigation of polymorphisms in innate and adaptive immune response genes in canine leishmaniosis

The outcome of infection with Leishmania infantum in dogs is variable, which is thought to be due to the nature of the immune response mounted by the host. As a consequence, the clinical signs and severity of canine leishmaniosis vary between individual dogs. Host immunogenetic factors might play an important role in determining the outcome of infection. The aim of this study was to examine polymorphisms in innate and adaptive immune response genes, to determine whether any of these were associated with susceptibility or resistance to L. infantum infection. Genomic DNA was obtained from two groups: pet dogs in endemic regions of Europe and a group of Beagles exposed to sand fly infection as part of a vaccine study. Genotyping was performed using a SNP (single nucleotide polymorphism) array for selected immune response genes. The first part of the study compared 62 clinical cases with 101 clinically unaffected dogs that were seronegative for Leishmania antibodies. One SNP in the CIITA gene demonstrated a significantly higher minor allele frequency in the case group, compared with the control group at the individual SNP level after permutation, but was not significant after correction for multiple testing. The second part of the study examined 48 Beagle dogs exposed to L. infantum over two transmission seasons. Twenty-seven dogs with a resistant phenotype (no evidence of clinical disease, seronegative at the end of the study period, negative on lymph node culture and only transiently PCR positive in bone marrow) were compared with 21 dogs demonstrating a susceptible phenotype (clinical disease, seropositive, positive lymph node culture and consistently PCR positive in bone marrow). Three SNPs in TLR3, two SNPs in PTPN22 and one SNP in TLR4 and IL1A were associated with the susceptible phenotype in the Beagle group at the individual SNP level after permutation analysis, but were not significant after correction for multiple testing. Further validation of these SNPs is required in a larger cohort of dogs, ideally with extreme phenotypes to confirm an association with the outcome of L. infantum infection

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

KELT-10b: The First Transiting Exoplanet From The KELT-South Survey - A Hot Sub-Jupiter Transiting A V=10.7 Early G-Star

We report the discovery of KELT-10b, the first transiting exoplanet discovered using the KELT-South telescope. KELT-10b is a highly inflated sub-Jupiter mass planet transiting a relatively bright V = 10.7 star (TYC 8378-64-1), with Teff = 5948 ± 74 K, log g = 4.319_{-0.030}^{+0.020} and [Fe/H] = 0.09_{-0.10}^{+0.11}, an inferred mass M★ = 1.112_{-0.061}^{+0.055} M☉ and radius R★ = 1.209_{-0.035}^{+0.047} R☉. The planet has a radius Rp = 1.399_{-0.049}^{+0.069} RJ and mass Mp = 0.679_{-0.038}^{+0.039} MJ. The planet has an eccentricity consistent with zero and a semi-major axis a = 0.05250_{-0.00097}^{+0.00086} AU. The best fitting linear ephemeris is T0 = 2457066.72045±0.00027 BJDTDB and P = 4.1662739±0.0000063 days. This planet joins a group of highly inflated transiting exoplanets with a radius larger and a mass less than that of Jupiter. The planet, which boasts deep transits of 1.4%, has a relatively high equilibrium temperature of Teq = 1377_{-23}^{+28} K, assuming zero albedo and perfect heat redistribution. KELT-10b receives an estimated insolation of 0.817_{-0.054}^{+0.068} × 109 erg s-1 cm-2, which places it far above the insolation threshold above which hot Jupiters exhibit increasing amounts of radius inflation. Evolutionary analysis of the host star suggests that KELT-10b may not survive beyond the current subgiant phase, depending on the rate of in-spiral of the planet over the next few Gyr. The planet transits a relatively bright star and exhibits the third largest transit depth of all transiting exoplanets with V 〈 11 in the southern hemisphere, making it a promising candidate for future atmospheric characterization studies

Adverse outcomes after colposcopy

Abstract Background Colposcopy is an essential part of the National Health Service Cervical Screening Programme (NHSCSP). It is used for both diagnosis and treatment of pre-cancerous cells of the cervix. Despite colposcopy being a commonly performed and relatively invasive procedure, very little research has explored the potential long-term impacts of colposcopic examination upon patient quality of life. The aim of this study is to investigate and quantify any potential reduction in women's quality of life following a colposcopy procedure. More specifically, the degree of female sexual dysfunction and the excess risk of adverse events in those undergoing colposcopy will be explored. If such risks are identified, these can be communicated to women before undergoing colposcopy. It will also assist in identifying whether there are particular sub-groups at greater risk and if so, this may lead to a re-evaluation of current recommendations concerning colposcopically directed treatments. Methods/design Cohort study using postal surveys to assess sexual function and quality of life in women who have attended for colposcopy (cases), compared with those who have not attended colposcopy (controls). The prevalence and excess risk of female sexual dysfunction will be determined. Logistic regression will identify the predictors of adverse outcomes. Discussion There are more than 400,000 colposcopy appointments each year in England, of which 134,000 are new referrals. There is some evidence that there may be long-term implications for women treated under colposcopy with respect to adverse obstetric outcomes, persisting anxiety, increased rates of sexual dysfunction and reduced quality of life. Reliably establishing whether such adverse outcomes exist and the excess risk of adverse events will facilitate informed decision-making and patient choice.</p

The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies